Abstract
In contemplating the future of aging, it is helpful to recognize that aging postponement, arrest, prevention, and reversal are commonplace but still under-appreciated natural and experimental phenomena. Aging is apparently completely preventable for prolonged periods in many whole animals by nutritional cues that are not confined to calorie restriction. Aging can be substantially postponed by interfering with active life-shortening processes that are triggered by sexual maturation and reproduction in most species, perhaps including humans, but, contrary to the idea that active life shortening is necessitated by a tradeoff against reproduction, aging can also be dramatically postponed by sexual maturation and reproduction (“negative reproductive costs”) in many species, including mammals. Many fundamental age-related changes are actually reversible in adults or adult systems by the application of simple physiological interventions (“segmental aging reversal”). These reversible elemental aspects of aging include, for example, reduced transcription, reduced translation, altered gene expression, reduced DNA repair, reduced mitochondrial function, reduced regenerative capacity, replicative senescence, lipofuscin accumulation, reduced immune function, thymic involution, loss of reproductive cycling in females, age-related organ atrophy, and hair graying and balding. In addition, many aging phenotypes appear to be interlinked, such that correction of one or a few central aging pathways leads to the correction of multiple downstream pathways without the need for specific intervention in any of these dependent pathways. Collectively, such observations reveal aging on multiple levels and in diverse phyla to be driven by biological mechanisms that are considerably more accessible than is classically expected. This body of observations implies that the future of human aging can be substantially different than its past and supports recent excitement over the possibilities of human intervention.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Abs R et al. (1999) GH replacement in 1034 growth hormone deficient hypopituitary adults: demographic and clinical characteristics, dosing and safety. Clin Endocrinol (Oxf) 50:703–713
Ailion M, Inoue T, Weaver CI, Holdcraft RW, Thomas JH (1999) Neurosecretory control of aging in Caenorhabditis elegans. Proc Nat Acad Sci 96:7394–7397
Alcain FJ, Minor RK, Villalba JM, de Cabo R (2010) Small molecule modulators of sirtuin activity. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 331–356
Amdam GV, Aase AL, Seehuus S-C, Kim-Fondrk M, Norberg K, Hartfelder K (2005) Social reversal of immunosenescence in honey bee workers. Exp Gerontol 40:939–947
Andersen B et al. (1995) The Ames dwarf gene is required for Pit-1 gene activation. Develop Biol 172:495–503
Anderson GL (1978) Response of dauer larvae of Caenorhabditis elegans (nematode: Rhabditidae) to thermal stress and oxygen deprivation. Can J Zool 56:1786–1791
Anisimov VN, Semenchenko AV, Yashin AI (2003) Insulin and longevity: antidiabetic biguanides as geroprotectors. Biogerontology 4:297–307
Anson RM et al. (2003) Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Nat Acad Sci 100:6116–6220
Apfeld J, Kenyon C (1998) Cell nonautonomy of C. elegans DAF-2 function in the regulation of diapause and life span. Cell 95:199–210
Apfeld J, Kenyon C (1999) Regulation of lifespan by sensory perception in Caenorhabditis elegans. Nature 402:804–809
Araneo B, Dowell T, Woods ML, Daynes R, Judd M, Evans T (1995) DHEAS as an effective vaccine adjuvant in elderly humans. Proof-of-principle studies. Ann NY Acad Sci 774:232–248
Arantes-Oliveira N, Apfeld J, Dillin A, Kenyon C (2002) Regulation of lifespan by germ-line stem cells in Caenorhabditis elegans. Science 295:502–505
Arantes-Oliveira N, Berman J, Kenyon C (2003) Healthy animals with extreme longevity. Science 302:611
Arking DE, Atzmon G, Arking A, Barzilai N, Dietz HC (2005) Association between a functional variant of the KLOTHO gene and high-density lipoprotein cholesterol, blood pressure, stroke, and longevity. Circulation Res 96:412–418
Arking DE et al. (2003) KLOTHO allele status and the risk of early-onset occult coronary artery disease. Am J Human Genet 72:1154–1161
Arking DE et al. (2002) Association of human aging with a functional variant of klotho. Proc Nat Acad Sci 99:856–861
Asencot M, Lensky Y (1984) Juvenile hormone induction of "queenliness" on female honey bee (Apis mellifera L.) larvae reared on worker jelly and on stored royal jelly. Comparative Biochem Physiol 78B:109–117
Aspinall R, Mitchell W (2010) Maintenance and restoration of immune system function. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer Science, Berlin, Heidelberg, New York, pp. 489–520
Atala A (2010) Life extension by tissue and organ replacement. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 543–571
Atzmon G et al. (2006) Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS Biol 4:e113
Austad SN, Kirkwood TBL (2008) Evolutionary theory in aging research. In: Guarente LP, Partridge L, Wallace DC (eds) Molecular Biology of Aging. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 95–111
Aviv A, Bogden JD (2010) Telomeres and the arithmetic of human longevity. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 573–586
Ayyadevara S, Alla R, Thaden JJ, Shmookler Reis RJ (2008) Remarkable longevity and stress resistance of nematode PI3K-null mutants. Aging Cell 7:13–22
Barger JL, Kayo T, Pugh TD, Prolla TA, Weindruch R (2008) Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart. Exp Gerontol 43:859–866
Barker K, Beveridge I, Bradley AJ, Lee AK (1978) Observations on spontaneous stress-related mortality among males of the dasyurid marsupial Antechinus stuartii (MacLeay). Aust J Zool 26:435–447
Barnett JL (1973) A stress response in Antechinus stuartii (MacLeay). Aust J Zool 21:501–513
Bartke A (1979) Prolactin-deficient mice. In: Alexander NJ (ed) Animal Models for Research on Contraception and Fertility. Harper & Row, Hagerstown, pp. 360–365
Bartke A, Brown-Borg HM (2004) Life extension in the dwarf mouse. Curr Topics Develop Biol 63:189–225
Bartke A, Wright JC, Mattison JA, Ingram DK, Miller RA, Roth GS (2001) Extending the lifespan of long-lived mice. Nature 414:412
Bauer ME (2005) Stress, glucocorticoids and ageing of the immune system. Stress 8:69–83
Baumeister R, Schaffitzel E, Hertweck M (2006) Endocrine signaling in Caenorhabditis elegans controls stress response and longevity. J Endocrinol 190:191–202
Baur JA et al. (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337–342
Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506
Baxter JD, Tyrrell JB (1987) The adrenal cortex. In: Felig P, Baxter JD, Boardus AE, Frohman LA (eds) Endocrinology and Metabolism, 2nd ed. McGraw-Hill Book Company, New York, pp. 511–650
Beck SD, Bharadwaj RK (1972) Reversed development and cellular aging in an insect. Science 178:1210–1211
Belchier M, Edsman L, Sheehy MRJ, Shelton PMJ (1998) Estimating age and growth of long-lived temperate freshwater crayfish using lipofuscin. Freshwater Biol 39:439–446
Bellino FL, Daynes RA, Hornsby PJ, Lavrin DH, Nestler JE (eds) (1995) Dehydroepiandrosterone (DHEA) and Aging. The New York Academy of Sciences, New York
Bergamini E, Cavallini G, Donati A, Gori Z (2003) The anti-ageing effects of caloric restriction may involve stimulation of macroautophagy and lysosomal degradation, and can be intensified pharmacologically. Biomed Pharmacother 57:203–208
Bergamini E, Cavallini G, Donati A, Gori Z (2004) The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases. Int J Biochem Cell Biol 36:2392–2404
Bergman A, Atzmon G, Ye K, MacCarthy T, Barzilai N (2007) Buffering mechanisms in aging: a systems approach toward uncovering the genetic component of aging. PLoS Comput Biol 3:e170
Bergquist DC, Williams FM, Fisher CR (2000) Longevity record for deep-sea invertebrate. Nature 403:499–500
Berman JR, Kenyon C (2006) Germ-cell loss extends C. elegans life span through regulation of DAF-16 by kri-1 and lipophilic-hormone signaling. Cell 124:1055–1068
Bertoni-Freddari C, Mervis RF, Giuli C, Pieri C (1985) Chronic dietary choline modulates synaptic plasticity in the cerebellar glomeruli of aging mice. Mechanisms of Ageing Develop 30:1–9
Beyer RE et al. (1985) Tissue Coenzyme Q (uniquinone) and protein concentration over the life span of the laboratory rat. Mechanisms of Ageing Develop 32:267–281
Bhalla P, Nehru B (2005) Modulatory effects of centrophenoxine on different regions of ageing rat brain. Exp Gerontol 40:801–806
Biddle FG, Eden SA, Rossler JS, Eales BA (1997) Sex and death in the mouse: genetically delayed reproduction and senescence. Genome 40:229–235
Bishop NA, Guarente L (2007) Two neurons mediate diet-restriction-induced longevity in C. elegans. Nature 447:545–549
Blackman MR, Sorkin JD, Munzer T et al. (2002) Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. J Am Med Assoc 288:2282–2292
Blazejowski CA, Webster GC (1983) Decreased rates of protein synthesis by cell-free preparations from different organs of aging mice. Mechanisms of Ageing Develop 21:345–356
Bliznakov EG (1978) Coenzyme Q deficiency in aged mice. J Med 9:337–346
Bliznakov EG (1981) Coenzyme Q, the immune system and aging. In: Folkers K, Yamamura Y (eds) Biomedical and Clinical Aspects of Coenzyme Q. Elsevier/North-Holland, Amsterdam, pp. 311–323
Bluher M, Kahn BB, Kahn CR (2003) Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299:572–574
Bluher M et al. (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Develop Cell 3:25–38
Bodnar AG et al. (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352
Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310:1954–1957
Boehm M, Slack FJ (2006) MicroRNA control of lifespan and metabolism. Cell Cycle 5:837–840
Bokov A, Chaudhuri A, Richardson A (2004) The role of oxidative damage and stress in aging. Mechanisms of Ageing Develop 125:811–826
Borowsky R (1978) Social inhibition of maturation in natural populations of Xiphophorus variatus (Pices: Poeciliidae). Science 201:933–935
Boulianne GL (2001) Neuronal regulation of lifespan: clues from flies and worms. Mech Ageing Develop 122:883–894
Brack AS et al. (2007) Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317:807–810
Bradley A, McDonald IR, Lee AK (1980) Stress and mortality in a small marsupial (Antechinus stuartii, Macleay). General and Comparative Endocrinol 40:188–200
Bredesen DE (2004) The non-existent aging program: how does it work? Aging Cell 3:255–259
Breeden S (1967) The Life of the Kangaroo. Taplinger, New York
Brizzee KR, Ordy JM, Kaach B (1974) Early appearance and regional differences in intraneuronal and extraneuronal lipofuscin accumulation with age in the brain of a nonhuman primate (Macaca mullata). J Gerontol 29:366–381
Brock MA, Strehler BL (1963) Studies on the comparative physiology of aging. 4. Age and mortality of some marine Cnidaria in the laboratory. J Gerontol 18:23–28
Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the aging process. Nature 384:33
Brown-Borg HM, Johnson WT, Rakoczy S, Romanick M (2001) Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice. J Am Aging Assoc 85:85–100
Brown-Borg HM, Rakoczy SG (2000) Catalase expression in delayed and premature aging mouse models. Exp Gerontol 35:199–212
Bruder CEG et al. (2008) Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles. Am J Human Genet 82:763–771
Budovskaya YV, Wu K, Southworth LK, Jiang M, Tedesco P, Johnson T (2008) An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell 134:291–303
Buffenstein R (2008) Negligible senescence in the longest-living rodent, the naked mole-rat: insights from a successfully aging species. J Comparative Physiol [B] 178:439–445
Buford TW, Willoughby DS (2008) Impact of DHEA(S) and cortisol on immune function in aging: a brief review. Appl Physiol Nutr Metab 33:429–433
Busbee DL, Sylvia VL, Norman JO et al. (1989) Age-related differences in DNA polymerase alpha specific activity: potential for interaction in DNA repair. In: Wang E, Warner HR (eds) Growth Control During Cell Aging. CRC Press, Boca Raton, pp. 65–87
Busbee DL, Sylvia VL, Stec J, Cernosek Z, Norman JO (1987) Lability of DNA polymerase alpha correlated with decreased DNA synthesis and increased age in human cells. J Natl Cancer Inst 79:1231–1239
Cabelof DC, Yanamadala S, Raffoul JJ, Guo Z, Soofi A, Heydari AR (2003) Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline. DNA Repair (Amst) 2:295–307
Cardarlli NF (1989) Involution, age, and puberty. In: Cardarelli NF (ed) The Thymus in Health and Senescence, Volume 1, Thymus and Immunity. CRC Press, Boca Raton, pp. 51–57
Carey JR, Liedo P, Orozco D, Vaupel JW (1992) Slowing of mortality rates at older ages in large medfly cohorts. Science 258:457–461
Carey JR, Liedo P, Vaupel JW (1995) Mortality dynamics of density in the Mediterranean fruit fly. Exp Gerontol 30:605–629
Carlson ME, Conboy MJ, Hsu M, Barchas L, Jeong J, Agrawal A, Mikels AJ, Agrawal S, Schaffer DV, Conboy IM (2009a) Relative roles of TGF-beta1 and Wnt in the systemic regulation and aging of satellite cell responses. Aging Cell 8:676–689
Carlson ME, Suetta C, Conboy MJ, Aagaard P, Mackey A, Kjaer M, Conboy I (2009b) Molecular aging and rejuvenation of human muscle stem cells. EMBO Molecular Med 1:381–391
Carrillo MC, Kanai S, Nokubo M, Ivy GO, Sato Y, Kitani K (1992) (-)Deprenyl increases activities of superoxide dismutase and catalase in striatum but not in hippocampus: the sex and age-related differences in the optimal dose in the rat. Exp Neurol 116:286–294
Castaneda M, Vargas R, Galvan SC (1986) Stagewise decline in the activity of brain protein synthesis factors and relationship between this decline and longevity in two rodent species. Mech Ageing Develop 36:197–210
Cavallini G, Donati A, Taddei M, Bergamini E (2007) Evidence for selective mitochondrial autophagy and failure in aging. Autophagy 3:26–27
Cavanagh JB, Nolan CC, Seville MP, Anderson VER, Leigh PN (1993) Routes of excretion of neuronal lysosomal dense bodies after ventricular infusion of leupeptin in the rat: a study using ubiquitin and PGP 9.5 immunocytochemistry. J Neurocytol 22:779–791
Cawthon RM, Smith KR, O’Brien E, al e (2003) Association between telomere length in blood and mortality in people aged 60 years or older. Lancet 361:393–395
Chan JM et al. (1998) Plasma insulin growth factor-1 and prostate cancer risk: a prospective study. Science 279:563–566
Chen D et al. (2002) Age-dependent decline of DNA repair activity for oxidative lesions in rat brain mitochondria. J Neurochem 81:1273–1284
Chen D, Minami M, Henshall DC, Meller R, Kisby G, Simon RP (2003) Upregulation of mitochondrial base-excision repair capability within rat brain after brief ischemia. J Cereb Blood Flow Metab 23:88–98
Cheng TC, Beamer WG, Phillip JA, Bartke A, Mallonee RL, Dowling C (1983) Etiology of growth hormone deficiency in little, Ames, and Snell dwarf mice. Endocrinology 113:1669–1678
Chiacchiera F, Simone C (2010) The AMPK-FoxO3A axis as a target for cancer treatment. Cell Cycle 9: (in press)
Choi IS, Cui Y, Koh Y-A, Lee H-C, Cho Y-B, Won Y-H (2008) Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics. Korean J Int Med 23:176–181
Christensen K, Johnson T, Vaupel JW (2006) The quest for genetic determinants of human longevity: challenges and insights. Nat Rev Genet 7:436–448
Chuang JC, Jones PA (2007) Epigenetics and microRNAs. Pediatric Res 61(5 Pt 2):24R–29R
Clark WR (2004) Reflections on an unsolved problem of biology: the evolution of senescence and death. Adv Gerontol 14:7–20
Cockburn A, Lee AK, Martin RW (1983) Macrogeographic variation in litter size in Antechinus (Marsupialia: Dasyuridae). Evolution 37:86–95
Coles LS, Harris SB (1996) Coenzyme Q-10 and lifespan extension. In: Klatz RM (ed) Advances in Anti-Aging Medicine. Liebert, New York, pp. 205–215
Comfort A (1979) The Biology of Senescence, 3rd ed. Elsevier, New York
Conboy IM, Conboy MJ, Smythe GM, Rando TA (2003) Notch-mediated restoration of regenerative potential to aged muscle. Science 302:1575–1577
Conboy IM, Conboy MJ, Wagers AJ, Girma ER, Weissman IL, Rando TA (2005) Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature 433:760–764
Congdon JD, Nagle RD, Kinney OM, van Loben Sells RC, Quinter T, Tinkle DW (2003) Testing hypotheses of aging in long-lived painted turtles (Chrysemys picta). Exp Gerontol 38:765–772
Congdon JD, Nagle RD, Kinney OM, Van Loben Sels RC (2001) Hypotheses of aging in a long-lived vertebrate, Blanding’s Turtle (Emydoidea blandingii). Exp Gerontol 36:813–828
Cooper RA, Uzmann JR (1977) Ecology of juvenile and adult clawed lobsters, Homarus americanus, Homarus gammarus, and Nephrops norvegicus. Circ-CSIRO Div Fish Oceanog 187–208
Corona M et al. (2007) Vitellogenin, juvenile hormone, insulin signaling, and queen honey bee longevity. Proc Nat Acad Sci 104:7128–7133
Corsini E et al. (2005) Age-related decline in RACK-1 expression in human leukocytes is correlated to plasma levels of dehydroepiandrosterone. J Leukocyte Biol 77:247–256
Cortina MS, Gordon WC, Lukiw WJ, Bazan NG (2005) Oxidative stress-induced retinal damage up-regulates DNA polymerase gamma and 8-oxoguanine-DNA-glycosylase in photoreceptor synaptic mitochondria. Exp Eye Res 81:742–750
Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ (2000) Assessment of growth parameters and lifespan of GHR/BP gene-disrupted mice. Endocrinology 141:2608–2613
Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ (2003) Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology 144:3799–3810
Cotzias GC, Miller ST, Nicholson AR Jr et al. (1974) Prolongation of the life-span in mice adapted to large amounts of L-Dopa. Proc Nat Acad Sci 71:2466–2469
Cotzias GC, Miller ST, Tang LC et al. (1977) Levodopa, fertility, and longevity. Science 196:549–550
Cui Z (2010) Near term prospects for broad spectrum amelioration of cancer. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 307–329
Curtsinger JW (1995) Density and age-specific mortality. Genetica 96:179–182
Cypser JR, Tedesco P, Wu D, Park S-K, Johnson T (2008) Secondary phenotypes associated with a GFP reporter that predicts increased survival in C. elegans. 37th Annual Meeting of the American Aging Association, Abstract 71
Dammann P, Burda H (2006a) Sexual activity and reproduction delay ageing in a mammal. Curr Biol 16:R117–R118
Dammann P, Burda H (2006b) Sexual activity and reproduction delay ageing in a mammal. Curr Biol 16:R117–R188
de Grey A (2010) WILT: Necessity, feasibility, affordability. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 667–684
de Grey ADNJ (2003) Critique of the demographic evidence for ‘late-life non-senescence’. Biochem Soc Trans 31:452–454
de la Cruz CP, Revilla E, Rodriguez-Gomez JA, Vizuete ML, Cano J, Machado A (1997) (-)-Deprenyl treatment restores serum insulin-like growth factor-I (IGF-I) levels in aged rats to young rat level. Eur J Pharmacol 327:215–220
de la Rosa O et al. (2006) Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 7:471–481
de Magalhaes JP, Church GM (2005) Genomes optimize reproduction: aging as a consequence of the developmental program. Physiology 20:252–259
de Souza-Pinto NC et al. (2001) Repair of 8-oxodeoxyguanosine lesions in mitochondrial DNA depends on the oxoguanine DNA glycosylase (OGG1) gene and 8-oxoguanine accumulates in the mitochondrial DNA of OGG1-defective mice. Cancer Res 61:5378–5381
Denckla WD (1975) A time to die. Life Science 16:31–44
Deyl Z, Juricova M, Stuchlikova E (1975) The effect of different nutritional regimes upon collagen concentration and survival of rats. Adv Exp Med Biol 53:359–369
Dhahbi JM, Kim HJ, Mote PL, Beaver RJ, Spindler SR (2004) Temporal linkage between the phenotypic and genomic responses to caloric restriction. Proc Nat Acad Sci 101:5524–5529
Dhahbi JM, Mote PL, Fahy GM, Spindler SR (2005) Identification of potential calorie restriction mimetics by microarray profiling. Physiol Genomics 23:343–350
Dhahbi JM, Tsuchiya T, Kim HJ, Mote PL, Spindler SR (2006) Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction. J Gerontol A Biol Sci Med Sci 61:218–231
Diamond JM (1982) Big-bang reproduction and aging in male marsupial mice. Nature 298:115–116
Dietz A, Hermann HR, Blum MS (1979) The role of exogenous JH I, JH III, and anti-JH (precocene II) on queen induction of 4.5-day-old worker honey bee larvae. J Insect Physiol 25:503–512
Dillin A et al. (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298:2398–2401
Dilman VM, Anisimov VN (1980) Effect of treatment with phenformin, diphenylhydantoin or L-DOPA on life span and tumor incidence in C3H/Sn mice. Gerontology 26:241–246
Domning DP (1983) Marching teeth of the manatee. Nat History 92:8–10
Domning DP (1987) Sea cow family reunion. Nat History 96:64–71
Donati A et al. (2008) In vivo effect of an antilipolytic drug (3,5'-dimethylpyrazole) on autophagic proteolysis and autophagy-related gene expression in rat liver. Biochem Biophys Res Commun 366:786–792
Donisthorpe H (1936) The oldest insect on record. Entomol Record J Variation 48:1–2
Druffel ERM et al. (1995) Gerardia: Bristlecone pine of the deep sea? Geochimica et Cosmochimica Acta 59:5031–5036
Dulloo AG, Gubler M, Montani JP, Seydoux J, Solinas G (2004) Substrate cycling between de novo lipogenesis and lipid oxidation: a thermogenic mechanism against skeletal muscle lipotoxicity and glucolipotoxicity. Int J Obesity-Related Metabolic Disorders 28:S29-S37
Easton DM (1997) Gompertz growth in number dead confirms medflies and nematodes show excess oldster survival. Exp Gerontol 32:719–726
Ebert TA (2008) Longevity and lack of senescence in the red sea urchin Strongylocentrotus franciscanus. Exp Gerontol 43:734–738
El-Ghazzawi E, Malaty HA (1975) Electron microscopic observations on extraneural lipofuscin in the monkey brain. Cell and Tissue Res 161:555–565
Elowitz MB, Levine AJ, Siggia ED, Swain PS (2002) Stochastic gene expression in a single cell. Science 297:1183–1186
Essers MA, de Vries-Smits LM, Barker N, Polderman PE, Burgering BM, Korswagen HC (2005) Functional interaction between beta-catechin and FOXO in oxidative stress signaling. Science 308:1181–1184
Ettienne G, Cony-Makhoul P, Mahon F-X (2002) Imatinib mesylate and gray hair. NE J Med 347:446
Evans GW, Meyer LK (1994) Life span is increased in rats supplemented with a chromium-pyridine 2 carboxylate complex. Adv Sci Res 1:19–23
Everitt A (1959) The effect of pituitary growth hormone on the aging male rat. J Gerontol 14:415–424
Fabris N, Mocchegiani E, Mariotti M, Pacini F, Pinchera A (1986) Thyroid function modulates thymic endocrine activity. J Clin Endocrinol Metab 62:474–478
Fabris N, Mocchegiani E, Muzzioli M, al e (1988) Neuroendocrine-thymus interactions: perspectives for intervention in aging. Annals NY Acad Sci 521:72–87
Fabris N, Mocchegiani E, Muzzioli M, al. e (1990) Zinc, immunity, and aging. In: Goldstein AL (ed) Biomedical Advances in Aging. Plenum, New York, pp. 271–281
Fabris N, Mocchegiani E, Provinciali M (1997) Plasticity of neuroendocrine-thymus interactions during aging. Exp Gerontol 32:415–429
Fabrizio P et al. (2004) Superoxide is a mediator of an altruistic aging program in Saccharomyces cerevisiae. J Cell Biol 166:1055–1067
Fahy GM (1985) Anti-aging conference report – part I. Anti-Aging News 5:1–5
Fahy GM (2001) Growth hormone therapy and related methods and pharmaceutical compositions. In: US Patent 6,297,212 B1
Fahy GM (2003) Apparent induction of partial thymic regeneration in a normal human subject: a case report. J Anti-Aging Med 6:219–227
Fedoroff N, Fontana W (2002) Small numbers of big molecules. Science 297:1129–1131
Fenton DA, English JS, Wilkinson JD (1982) Reversal of male-pattern baldness, hypertrichosis, and accelerated hair and nail growth in patients receiving benoxaprofen. Br Med J 284:1228–1229
Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114
Finch CE (1990) Longevity, Senescence, and the Genome. The University of Chicago Press, Chicago
Flatt T et al. (2008) Drosophila germ-line modulation of insulin signaling and lifespan. Proc Nat Acad Sci 105:6368–6373
Flatt T, Tu MP, Tatar M (2005) Hormonal pleiotropy and the juvenile hormone regulation of Drosophila development and life history. Bioessays 27:999–1010
Flurkey K, Papaconstantinou J, Miller RA, Harrison DE (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Nat Acad Sci 98:6736–6741
Fonseca DB, Sheehy MR, Blackman N, Shelton PM, Prior AE (2005) Reversal of a hallmark of brain ageing: lipofuscin accumulation. Neurobiol Aging 26:69–76
Fonseca DB, Sheehy MRJ, Shelton PMJ (2003) Unilateral eyestalk ablation reduces neurolipofuscin accumulation rate in the contra-lateral eyestalk of a crustacean Pacifastacus leniusculus. J Exp Mar Biol Ecol 289:277–286
Foster RB (1977) Tachigalia versicolor is a suicidal neotropical tree. Nature 268:624–626
Fraga CG, Shigenaga MK, Park J-W, Degan P, Ames BN (1990) Oxidative damage to DNA during aging: 8-hydroxy-2'-deoxyguanosine in rat organ DNA and urine. Proc Nat Acad Sci 87:4533–4537
Fraga MF et al. (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Nat Acad Sci 102:10604–10609
Freitas R, Jr (2010) Comprehensive nanorobotic control of human morbidity and aging. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 685–805
Fry M, Loeb LA (1986) Animal Cell DNA Polymerases. CRC Press, Boca Raton
Furber JD (2010) Repairing extracellular aging and glycation. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 587–621
Gadaleta MN et al. (1994) Mitochondrial DNA transcription and translation in aged rat. Annals NY Acad Sci 717:150–160
Gadaleta MN, Petruzzella V, Renis M, Fracasso F, Cantatore P (1990) Reduced transcription of mitochondrial DNA in the senescent rat. Tissue dependence and effect of L-carnitine. Eur J Biochem 187:501–506
Gami MS, Wolkow CA (2006) Studies of Caenorhabditis elegans DAF-2/insulin signaling reveal targets for pharmacological manipulation of lifespan. Aging Cell 5:31–37
Gavrilov LA, Gavrilova NS (1991) The Biology of Lifespan: A Quantitative Approach. Harwood Academic Publishers, New York
George JC et al. (1999) Age and growth estimates of bowhead whales (Balaena mysticetus) via aspartic acid racemization. Can J Zool 77:571–580
Gershon D (1979) Current status of age altered enzymes: alternative mechanisms. Mech Ageing Dev 9:189–196
Gibbons JW (1987) Why do turtles live so long? BioScience 37:262–269
Gilleard JS, McGhee JD (2001) Activation of hypodermal differentiation in the Caenorhabditis elegans embryo by GATA transcription factors ELT-1 and ELT-3. Mol Cell Biol 21:2533–2544
Giuli C, Bertoni-Freddari C, Pieri C (1980) Morphometric studies on synapses of the cerebellar glomerulus: the effect of centrophenoxine treatment in old rats. Mech Ageing Develop 14:265–271
Glees P, Spoerri PE (1975) Centrophenoxin-induced dissolution and removal of lipofuscin. An electron microscopic study. Arzneimittelforschung 25:1543–1548
Godfrey P, Rahal JO, Beamer WG, Copeland NG, Jenkins NA, Mayo KE (1993) GHRH receptor of little mice contains a missense mutation in the extracellular domain that disrupts receptor function. Nat Genet 4:227–232
Goff BL, Roth JA, Arp LH, al. e (1987) Growth hormone treatment stimulates thymulin production in aged dogs. Clin Exp Immunol 68:580–587
Golembiowska K, Dziubina A, Kowalska M, Kaminska K (2008) Paradoxical effects of adenosine receptor ligands on hydroxyl radical generation by L-DOPA in the rat striatum. Pharmacol Rep 60:319–330
Goodrick CL, Ingram DK, Reynolds MA, Freeman JR, Cider N (1990) Effects of intermittent feeding upon body weight and lifespan in inbred mice: interaction of genotype and age. Mech Ageing Develop 55:69–87
Goto S, Takahashi R, Araki S, Nakamoto H (2002) Dietary restriction initiated in late adulthood can reverse age-related alterations of protein and protein metabolism. Annals NY Acad Sci 959:50–56
Goto S et al. (2001) Implications of protein degradation in aging. Annals NY Acad Sci 928:54–64
Goto S, Takahashi R, Radak Z, Sharma R (2007) Beneficial biochemical outcomes of late-onset dietary restriction in rodents. Annals NY Acad Sci 1100:431–441
Greenstein BD, de Bridges EF, Fitzpatrick FTA (1992) Aromatase inhibitors regenerate the thymus in aging male rats. Int J Immunopharmacol 14:541–553
Greenstein BD, Fitzpatrick FT, Kendall MD, Wheeler MJ (1987) Regeneration of the thymus in old male rats treated with a stable analogue of LHRH. J Endocrinol 112:345–350
Greenwood M, Irwin JO (1939) Biostatistics of senility. Human Biol 11:1–23
Growth Hormone Research Society (2001) Critical evaluation of the safety of recombinant human growth hormone administration: Statement from the Growth Hormone Research Society. J Clin Endrocrinol Metab 86:1868–1870
Gruneberg H (1952) The Genetics of the Mouse. Martinus Nijhoff, The Hague
Guo Z, Heydari A, Richardson A (1998) Nucleotide excision repair of actively transcribed versus nontranscribed DNA in rat hepatocytes: effect of age and dietary restriction. Exp Cell Res 245:228–238
Hadrup SR et al. (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 176:2645–2653
Hakimi P et al. (2007) Overexpression of the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) in skeletal muscle repatterns energy metabolism in the mouse. J Biol Chem 282:32844–32855
Hamilton JB, Hamilton RS, Mestler GE (1969) Duration of life in domestic cats: influence of sex, gonadectomy, and inbreeding. J Gerontol 24:427–437
Hamilton JB, Mestler GF (1969) Mortality and survival: comparison of eunuchs with intact men and women in a mentally retarded population. J Gerontol 24:395–411
Hampl R, Starka L, Jansky L (2006) Steroids and thermogenesis. Physiol Res 55:123–131
Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4:e24 (21–14)
Hansen M, Taubert S, Crawford D, Libina N, Lee S-J, Kenyon C (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6:95–110
Hanson RW, Hakimi P (2008) Born to run; the story of the PEPCK-C (mus) mouse. Biochimie 90:838–842
Hardie DG (2007) AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8
Harper JL (1977) Population Biology of Plants. Academic Press, New York
Harrison DE et al. (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395
Harshman LG (1999) Investigation of the endocrine system in extended longevity lines of Drosophila melanogaster. Exp Gerontol 34:997–1006
Haskins CP (1960) Note on the natural longevity of fertile females of Aphaenogaster picea. NY Entomol Soc 58:66–67
Hauck SJ, Bartke A (2001) Effects of growth hormone on hypothalamic catalase and Cu/Zn superoxide dismutase. Free Radicals Biol Med 28:970–978
Hayakawa K et al. (1992) Intrapair differences of physical aging and longevity in identical twins. Acta Genet Med Gemellol (Roma) 41:177–185
Hayashi J-I et al. (1994) Nuclear but not mitochondrial genome involvement in human age-related mitochondrial dysfunction: functional integrity of mitochondrial DNA from aged subjects. J Biol Chem 269:6878–6883
Herman WS, Tatar M (2001) Juvenile hormone regulation of longevity in the migratory monarch butterfly. Proc Royal Soc London B 268:2509–2514
Herndon LA et al. (2002) Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419:808–814
Heward CB (2010) An approach to extending human lifespan today. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York
Hirokawa K, Utsuyama M (1984) The effect of sequential multiple grafting of syngeneic newborn thymus on the immune functions and life expectancy of aging mice. Mech Ageing Develop 28:111–121
Hjelmborg J, Iachine I, Skytthe A, Vaupel JW, McGue M, al. e (2006) Genetic influence on human lifespan and longevity. Human Genet 119:312–321
Hochschild R (1971) Effect of membrane stabilizing drugs on mortality in Drosophila melanogaster. Exp Gerontol 6:133–151
Hochschild R (1973a) Effect of dimethylaminoethanol on the life span of senile male A-J mice. Exp Gerontol 8:185–191
Hochschild R (1973b) Effect of dimethylaminoethyl p-chlorophenoxyacetate on the life span of male Swiss Webster Albino mice. Exp Gerontol 8:177–183
Hodkova M (2008) Tissue signaling pathways in the regulation of life-span and reproduction in females of the linden bug, Pyrrhocoris apterus. J Insect Physiol 54:508–517
Holden C (1987) Why do women live longer than men? Science 238:158–160
Holliday R (2006) Epigenetics: a historical overview. Epigenetics 1:76–80
Holtzenberger M et al. (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–187
Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 13:1385–1393
Houthoofd K et al. (2002) Ageing is reversed, and metabolism is reset to young levels in recovering dauer larvae of C. elegans. Exp Gerontol 37:1015–1021
Howitz KT et al. (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425:191–196
Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:308–309
Huang H, Tindall DJ (2007) Dynamic FoxO transcription factors. J Cell Sci 120:2479–2487
Huang HH, Marshall S, Meites J (1976) Induction of estrous cycles in old non-cyclic rats by progesterone, ACTH, ether stress, or L-dopa. Neuroendocrinology 20:21–34
Hudson G, Chinnery PF (2006) Mitochondrial DNA polymerase-gamma and human disease. Hum Mol Genet 15 Spec No 2:R244-R252
Hunter WS, Croson WB, Bartke A, Gentry MV, Meliska CJ (1999) Low body temperature in long-lived Ames dwarf mice at rest and during stress. Physiol Behav 67:433–437
Hwangbo DS, Gersham B, Tu MP, Palmer M, Tatar M (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429:562–566
Hyun M, Lee J, Lee K, May A, Bohr VA, Ahn B (2008) Longevity and resistance to stress correlate with DNA repair capacity in Caenorhabditis elegans. Nucleic Acids Res 36:1380–1389
Ikeda E et al. (2009) Fully functional bioengineered tooth replacement as an organ replacement therapy. PNAS 106:13475–13480
Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A (2003) Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci 58:B5–B12
Iliadou A, Lichtenstein P, de Faire U, Pedersen NL (2001) Variation in genetic and environmental influences in serum lipid and apolipoprotein levels across the lifespan in Swedish male and female twins. Am J Med Genet 102:48–58
Iossa S, Mollica MP, Lionetti L, Crescenzo R, Tasso R, Liverini G (2004) A possible link between skeletal muscle mitochondrial efficiency and age-induced insulin resistance. Diabetes 53:2861–2866
Ivy GO, Roopsingh R, Kanai S, Ohta M, Sato Y, Kitani K (1996) Leupeptin causes an accumulation of lipofuscin-like substances and other signs of aging in kidneys of young rats: further evidence for the protease inhibitor model of aging. Annals NY Acad Sci 786:12–23
Ivy GO, Schottler F, Wenzel J, Baudry M, Lynch G (1984) Inhibitors of lysosomal enzymes: accumulation of lipofuscin-like dense bodies in the brain. Science 226:985–987
Izumikawa M et al. (2005) Auditory hair cell replacement and hearing improvement by Atoh1 gene therapy in deaf mammals. Nat Med 11:271–276
Jackson D, Leys SP, Hinman VF, Woods R, Lavin MF, Degnan BM (2002) Ecological regulation of development: induction of marine invertebrate metamorphosis. Int J Develop Biol 46:679–686
Janzen DH (1976) Why bamboos wait so long to flower. Ann Rev Ecol Syst 7:347–391
Johannsson G, Jørgensen J (2001) Safety aspects of growth hormone replacement in adults. Growth Horm IGF Res 11:59–71
Johnson L, Hawkins JE, Jr (1972) Sensory and neuronal degeneration with aging, as seen in microdissections of the human inner ear. Ann Otol 81:178–183
Johnson T, Mitchell D, Kline S, Kemal R, Foy J (1984) Arresting development arrests aging in the nematode Caenorhabditis elegans. Mech Ageing Develop 28:23–40
Jones DS (1983) Sclerochronology: Reading the record of the molluscan shell. Am Sci 71:384–391
Judd R, Bueso-Ramos C (1990) Combined true thymic hyperplasia and lymphoid hyperplasia in Grave’s disease. Pediatric Pathol 10:829–836
Kaeberlein M, Jegalian B, McVey M (2002) AGEID: a database of aging genes and interventions. Mech Ageing Develop 123:1115–1119
Kaeberlein M, Kennedy BK (2009) A midlife longevity drug? Nature 460:331–332
Kalimi M, Regelson W (eds) (1990) The Biologic Role of Dehydroepiandrosterone (DHEA). Walter de Gruyter, New York
Kalu DN et al. (1998) Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity. J Gerontol A Biol Sci Med Sci 53:B452-B463
Kaminsky Z et al. (2008) Epigenetics of personality traits: an illustrative study of identical twins discordant for risk-taking behavior. Twin Res Hum Genet 11:1–11
Kaminsky ZA et al. (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41:240–245
Kato M, Slack FJ (2008) microRNAs: small molecules with big roles – C. elegans to human cancer. Biol Cell 100:71–81
Katz ML, Rice LM, Gao CL (1999) Reversible accumulation of lipofuscin-like inclusions in the retinal pigment epithelium. Invest Ophthalmol Vis Sci 40:175–181
Kelley KW, Brief S, Westly HJ, al e (1986) GH3 pituitary adenoma cells can reverse thymic aging in rats. Proc Nat Acad Sci 83:5663–5667
Kenyon C (2006) My adventures with genes from the fountain of youth. The Harvey Lectures Series 100:29–70
Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512
Keogh EV, Walsh R (1965) Rate of graying of human hair. Nature 207:877–878
Khansari DN, Gustad T (1991) Effecs of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice. Mech Ageing Develop 57:87–100
Khaw KT et al. (2007) Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 116:2694–2701
Kinney BA, Meliska CJ, Steger RW, Bartke A (2001) Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters. Hormones and Behavior 39:277–284
Kiray M et al. (2006) Deprenyl and the relationship between its effects on spatial memory, oxidant stress and hippocampal neurons in aged male rats. Physiol Res 55:205–212
Kirkwood TBL (1977) Evolution of ageing. Nature 270:301–304
Kirkwood TBL, Finch CE (2002) The old worm turns more slowly. Nature 419:794–795
Kitani K, Kanai S, Ivy GO, Carrillo MC (1999) Pharmacological modifications of endogenous antioxidant enzymes with special reference to the effects of deprenyl: a possible antioxidant strategy. Mech Ageing Develop 111:211–221
Kitani K, Kanai S, Miyasaka K, Carrillo MC, Ivy GO (2006) The necessity of having a proper dose of (-)deprenyl (D) to prolong the life spans of rats explains discrepancies among different studies in the past. Annals NY Acad Sci 1067:375–382
Kitani K, Kanai S, Sato Y, Ohta M, Ivy GO, Carrillo MC (1993) Chronic treatment of (-)deprenyl prolongs the life span of male Fischer 344 rats. Further evidence. Life Sci 52:281–288
Kitani K et al. (2002) Why (-)deprenyl prolongs survivals of experimental animals: increase of anti-oxidant enzymes in brain and other body tissues as well as mobilization of various humoral factors may lead to systemic anti-aging effects. Mech Ageing Develop 123:1087–1100
Klass M, Hirsh D (1976) Non-ageing developmental variant of Caenorhabditis elegans. Nature 260:523–525
Klebanov S et al. (2000) Heritability of life span in mice and its implication for direct and indirect selection for longevity. Genetica 110:209–218
Klungland A et al. (1999) Accumulation of premutagenic DNA lesions in mice defective in removal of oxidative base damage. Proc Nat Acad Sci 96:13300–13305
Knoll J (1988) The striatal dopamine dependency of life span in male rats. Longevity study with (-)deprenyl. Mech Ageing Develop 46:237–262
Koh K, Rothman JH (2001) ELT-5 and ELT-6 are required continuously to regulate epidermal seam cell differentiation and cell fusion in C. elegans. Development 128:2867–2880
Kopchick JJ, Bartke A, Berryman DE (2008) Extended life span in mice with reduction in the GH/IGF-1 axis. In: Guarente LP, Partridge L, Wallace DC (eds) Molecular Biology of Aging. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 347–369
Kren BT, Bandyopadhyay P, Steer CJ (1998) In vivo site-directed mutagenesis of the factor IX gene by chimeric RNA/DNA oligonucleotides. Nat Med 4:285–290
Kujoth GC et al. (2005) Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 309:481–484
Kuratomi G et al. (2008) Aberrant DNA methylation associated with bipolar disorder identified from discordant monozygotic twins. Mol Psychiatr 13:429–441
Kurosu H et al. (2005) Suppression of aging in mice by the hormone klotho. Science 309:1829–1833
Lagouge M et al. (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell 127:1109–1122
LaMarche VC (1969) Environment in relation to age of bristlecome pines. Ecology 50:53–59
Lambert AJ, Merry BJ (2004) Effect of calorie restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin. Am J Physiol Regulatory Integrative Comparative Physiol 286:R71–R79
Lardy H, Kneer N, Bellei M, Bobyleva V (1995) Induction of thermogenic enzymes by DHEA and its metabolites. Annals NY Acad Sci 774
Larsen LO (1965) Effects of hypophysectomy in the cyclostome, Lampetra fluviatilis (L.) Gray. General Comparative Endocrinol 5:16–30
Larsen LO (1969) Effects of hypophysectomy before and during sexual maturation in the cyclostome, Lampetra fluviatilis L. Gray. General Comparative Endocrinol 12:200–208
Larsen LO (1974) Effects of testosterone and oestradiol on gonadectomized and intact male and female river lampreys (Lampetra fluviatilis L. Gray). General Comparative Endocrinol 24:305–313
Larsen LO (1985) The role of hormones in reproduction and death in lampreys and other species which reproduce once and die. In: Lofts B, Holmes WN (eds) Current Trends in Comparative Endocrinology. Hong Kong University Press, Hong Kong, pp. 613–616
Larson LO (1980) Physiology of adult lampreys, with special regard to natural starvation, reproduction, and death after spawning. Can J Fish Aquatic Sci 37:1762–1779
Lea-Currie YR, Wu SM, McIntosh MK (1997) Effects of acute administration of dehydroepiandrosterone-sulfate on adipose tissue mass and cellularity in male rats. Int J Obesity-Related Metabolic Disorders 21:147–154
Leaman BM, Beamish RJ (1984) Ecological and management implications of longevity in some northeast Pacific ground-fishes. Bull Int N Pac Fish Commn 42:85–97
LeBlanc J, Arvaniti K, Richard D (1998) Effect of dehydroepiandrosterone on brown adipose tissue and energy balance in mice. Hormone and Metabolism Res 30:236–240
Ledford H (2010) Much ado about ageing. Nature 464:480–481
Lee AK, Cockburn A (1985a) Evolutionary Ecology of Marsupials. Cambridge University Press, New York
Lee AK, Cockburn A (1985b) Spring declines in small mammal populations. Acta Zoologica Fennica 173:75–76
Lee CK et al. (2004) The impact of alpha-lipoic acid, coenyzme Q10 and calorie restriction on life span and gene expression patterns in mice. Free Radicals Biol Med 36:1043–1057
Leopold AC (1961) Senescence in plant development: the death of plants or plant parts may be of positive ecological or physiological value. Science 134:1727–1732
Leopold AC, Niedergang-Kamien E, Janick J (1959) Experimental modification of plant senescence. Plant Physiol 34:570–573
Lesnefsky EJ, He D, Moghadas S, Hoppel CL (2006) Reversal of mitochondrial defects before ischemia protects the aged heart. FASEB J 20:E840–E845
Lewis SE, Goldspink DF, Phillips JG, Merry BJ, Holehan AM (1985) The effects of aging and chronic dietary restriction on whole body growth and protein turnover in the rat. Exp Gerontol 20:253–263
Liang H, Masoro EJ, Nelson JF, Strong R, McMahan CA, Richardson A (2003) Genetic mouse models of extended lifespan. Exp Gerontol 38:1353–1364
Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, Pletcher SD (2007) Regulation of Drosophila life span by olfaction and food-derived odors. Science 315:1133–1137
Licastro F, Weindruch R, Davis LJ, Walford RL (1988) Effect of dietary restriction upon the age-associated decline of lymphocyte DNA repair activity in mice. AGE 11:48–52
Lindell TJ (1982) Current concepts: III. Molecular aspects of dietary modulation of transcription and enhanced longevity. Life Sci 31:625–635
Lindseth K, Philpott D, Miquel J (1984) Accelerated aging under simulated hypergravity: protection by dietary enrichment. AGE 7:140
Linn S, Kairis M, Holiday R (1981) Decreased fidelity of DNA polymerase activity isolated from aging human fibroblasts. J Mol Biol 146:2818–2822
Lipman JM, Turturo A, Hart RW (1989) The influence of dietary restriction on DNA repair in rodents: a preliminary study. Mech Ageing Develop 48:135–143
Ljungquist B, Berg S, Lanke J, McClearn GE, Pedersen NL (1998) The effect of genetic factors for longevity: a comparison of identical and fraternal twins in the Swedish Twin Registry. J Gerontol A Biol Sci Med Sci 53:M441-M446
Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342–1346
Longo VD, Mitteldorf J, Skulachev VP (2005) Programmed and altruistic ageing. Nat Rev Genet 6:866–872
Lu T et al. (2004) Gene regulation and DNA damage in the ageing human brain. Nature 429:883–891
Ludwig-Festl VM, Grater B, Bayreuther K (1983) Erhohung von Zellstoffwechselleistungen in normalen, diploiden, menschlichen Glia-Zellen in stationaren Zellkulturen induziert durch Meclofenoxat. Arzneim-Forsch 33:495–501
Maccari F, Arseni A, Chiodi P, Ramacci MT, Angelucci L (1990) Levels of carnitines in brain and other tissues of rats of different ages: effect of acetyl-L-carnitine administration. Exp Gerontol 25:127–134
Macchi MM, Bruce JN (2004) Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol 25:177–195
MacGillivray MH (1987) Disorders of growth and development. In: Felig P, Baxter JD, Broadus AE, Frohman LA (eds) Endocrinology and Metabolism, 2nd ed. McGraw-Hill Book Company, New York, pp. 1581–1628
MacKay IR, Whittingham SF, Mathews JD (1977) The immunoepidemiology of aging. In: Makinodan T, Yunis E (eds) Immunology and Aging. Plenum, New York, pp. 35–49
Maier H, Gampe J, Jeune B, Robine J-M, Vaupel JW (2010) Supercentenarians (Springer, in press)
Manion PJ, Smith BR (1978) Biology of larval and metamorphosing sea lampreys, Petromyzon marinus, of the 1960 year class in the Big Garlic River, Michigan: Part 2, 1966–1972. Great Lakes Fisheries Commission
Martin GM (1979) Genetic and evolutionary aspects of aging. Federation Proc 38:1962–1967
Martin GM, Bergman A, Barzilai N (2007) Genetic determinants of human health span and life span: progress and new opportunities. PLOS Genet 3:1121–1130
Martin GM, Finch CE (2008) An overview of the biology of aging: a human perspective. In: Guarente LP, Partridge L, Wallace DC (eds) Molecular Biology of Aging. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 113–126
Martinez-Vicente M, Cuervo AM (2007) Autophagy and neurodegeneration: when the cleaning crew goes on strike. Lancet Neurol 6:352–361
Mattick JS, Makunin IV (2006) Non-coding RNA. Human Molecular Genetics 15 (Spec No 1):R17–R29
Mattson M, Duan W, Maswood N (2002) How does the brain control lifespan? Ageing Res Rev 1:155–165
Maule AG, Schreck CB (1987) Changes in the immune system of coho salmon (Oncorhynchus kisutch) during the parr-to-smolt transformation and after implantation of cortisol. Can J Fish Aquatic Sci 44:161–166
McBride JR, van Overbeeke AP (1969) Hypertrophy of the interrenal tissue in sexually maturing Sockeye salmon (Oncorhynchus nerka) and the effect of gonadectomy. J Fish Res Board Canada 26:2975–2985
McDonald RB, Florez-Duquet M, Murtagh-Mark C, Norwitz BA (1996) Relationship between cold-induced thermoregulation and spontaneous rapid body weight loss of aging F344 rats. Am J Physiol 271 (5 Pt 2):R1115–R1122
Meites J (1991) Role of hypothalamic catecholamines in aging processes. Acta Endocrinol (Copenh) 125(Suppl 1):98–103
Meites J (1993) Anti-ageing interventions and their neuroendocrine aspects in mammals. J Reprod Fert Suppl 46:1–9
Mervis RF, Pope D, Lewis R, Dvorak RM, Williams LR (1991) Exogenous nerve growth factor reverses age-related structural changes in neocortical neurons in the aging rat. A quantitative Golgi study. Ann NY Acad Sci 640:95–101
Metayer S et al. (2008) Mechanisms through which sulfur amino acids control protein metabolism and oxidative status. J Nutr Biochem 19:207–215
Michikawa Y, Mazzuchelli F, Bresolin N, Scarlato G, Attardi G (1999) Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication. Science 286:774–779
Migliaccio E et al. (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402:309–313
Migliaccio E et al. (1997) Opposite effects of the p52shc/p46shc and p66shc splicing isoforms on the EGF receptor-MAP kinase-fos signalling pathway. EMBO J 16:706–716
Milgram NW, Racine RJ, Nellis P, Mendonca A, Ivy GO (1990) Maintenance on L-deprenyl prolongs life in aged male rats. Life Sci 47:415–420
Miller SE, Hadfield MG (1990) Developmental arrest during larval life and life-span extension in a marine mollusc. Science 248:356–358
Min KJ, Yamamoto R, Buch S, Pankratz M, Tatar M (2008) Drosophila lifespan control by dietary restriction independent of insulin-like signaling. Aging Cell 7:199–206
Mitteldorf J (2004) Aging selected for its own sake. Evol Ecol Res 6:1–17
Mitteldorf J (2010) Evolutionary origins of aging. In: Fahy Gm, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 87–126
Molisch H (1938) The Longevity of Plants. Science Press, Lancaster, PA
Monteiro RAF (1991) Genesis, structure and transit of dense bodies in rat neocerebellar cortical-cells, namely purkinje neurons – an ultrastructural study. J Hirnforsch 32:593–609
Moore GH (1974) Aetiology of the die-off of male Antechinus stuartii. In: (Ph.D. dissertation). Australian National University, Canberra
Moroi-Fetters SE, Mervis RF, London ED, Ingram DK (1989) Dietary restriction suppresses age related changes in dendritic spines. Neurobiol Aging 10:317–322
Mueller LD, Rose MR (1996) Evolutionary theory predicts late-life mortality plateaus. Proc Nat Acad Sci 93:15249–15253
Murasko DM, Weiner P, Kaye D (1987) Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 70:440–448
Murasko DM, Weiner P, Kaye D (1988) Association of lack of mitogen induced lymphocyte proliferation with increased mortality in the elderly. Aging, Immunol Infectious Dis 1:1–6
Murphy CT et al. (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–283
Nakada K, Ono T, Hayashi J (2002) A novel defense system of mitochondria in mice and human subjects for preventing expression of mitochondrial dysfunction by pathogenic mutant mtDNAs. Mitochondrion 2:59–70
Napoli C et al. (2003) Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Nat Acad Sci 100:2112–2116
Napolitano LA, Lo JC, Gotway MB et al. (2002) Increased thymic mass and circulating naive CD4 T cells in HIV-1-infected adults treated with growth hormone. AIDS 15:1103–1111
Narkar VA et al. (2008) AMPK and PPARgamma agonists are exercise mimetics. Cell 134:405–415
Nemoto S, Finkel T (2002) Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science 295:2450–2452
Niedernhofer LJ et al. (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444:1038–1043
Nishimura EK, Granter SR, Fisher DE (2005) Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science 307:720–724
Nooden LD (1988) Whole plant senescence. In: Nooden LD, Leopold AC (eds) Senescence and Aging in Plants. Academic Press, San Diego
Norton NW, Racine RJ, Nellis P, Mendonca A, Ivy GO (1990) Maintenance on L-deprenyl prolongs life in aged male rats. Life Science 47
Oka HI (1976) Mortality and adaptive mechanisms of Oryza perennis strains. Evolution 30:380–392
Ono K, Hasegawa K, Naiki H, Yamada M (2006) Anti-Parkinsonian agents have anti-amyloidogenic activity for Alzheimer’s beta-amyloid fibrils in vitro. Neurochem Int 48:275–285
Ooka H, Segall PE, Timiras PA (1988) Histology and survival in age-delayed low-tryptophan-fed rats. Mech Ageing Develop 43:79–98
Orentreich N, Matias JR, deFelice A, Zimmerman JA (1993) Low methionine ingestion by rats extends life span. J Nutr 123:269–274
Pacholec M et al. (2010) SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 285:8340–8351
Pan KZ et al. (2007) Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6:111–119
Paradies G, Ruggiero FM, Petrosillo G, Gadaleta MN, Quagliariello E (1994) The effect of aging and acetyl-L-carnitine on the function and on the lipid composition of rat heart mitochondria. Annals NY Acad Sci 717:233–243
Partridge L, Mangel M (1999) Messages from mortality: the evolution of death rates in the old. Trends Ecol Evol 14:438–442
Patro N, Sharma SP, Patro IK (1992) Lipofuscin accumulation in ageing myocardium & its removal by meclophenoxate. Indian J Med Res 96:192–198
Pearson KJ et al. (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metabolism 8:157–168
Pener MP (1972) The corpus allatum in adult acrilids: the inter-relation of its functions and possible correlations with the life cycle. In: Hemming CF, Taylor THC (eds) Proceedings of the International Study Conference on the Current and Future Problems of Acridology. Center for Overseas Pest Research, London, pp. 135–147
Perls T, Levenson R, Regan M, Puca A (2002a) What does it take to live to 100? Mech Ageing Develop 123:231–242
Perls T, Puca A (2002) The genetics of aging – implications for pharmacogenomics. Pharmacogenomics 3:469–484
Perls TT, Wilmoth J, Levenson R, Drinkwater M, M C, al. e (2002b) Life-long sustained mortality advantage of siblings of centenarians. Proc Nat Acad Sci 99:8442–8447
Pickering AD (1976) Stimulation of intestinal degeneration by oestradiol and testosterone implantation in the migrating river lambry, Lampetra fluviatilis L. General Comparative Endocrinol 30:340–346
Pierpaoli W (ed) (2005) Reversal of Aging, Resetting the Pineal Clock. New York Academy of Sciences, New York
Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha): transcriptional coactivator and metabolic regulator. Endrocr Rev 24:78–90
Quigley K, Goya R, Meites J (1987) Rejuvenating effects of 10-week underfeeding period on estrous cycles in young and old rats. Neurobiol Aging 8:225–232
Rao G, Xia E, Nadakavukaren MJ, Richardson A (1990a) Effect of dietary restriction on the age-dependent changes in the expression of antioxidant enzymes in rat liver. J Nutr 120: 602–609
Rao G, Xia E, Richardson A (1990b) Effect of age on the expression of antioxidant enzymes in male Fischer F344 rats. Mech Ageing Dev 31:49–60
Raser JM, O’Shea EK (2005) Noise in gene expression: origins, consequences, and control. Science 309:2010–2013
Raven PH, Evert RF, Eichhorn SE (1986) Biology of Plants, 4th ed. Worth, New York
Rea SL, Wu D, Cypser JR, Vaupel JW, Johnson T (2005) A stress-sensitive reporter predicts longevity in isogenic populations of Caenorhabditis elegans. Nat Genet 37:894–898
Redondo P et al. (2007) Repigmentation of gray hair after thyroid hormone treatment. Actas Dermosifiliogr 98:603–610
Richardson A, Liu F, Adamo ML, van Remmen H, Nelson JF (2004) The role of insulin and insulin-like growth factor-1 in mammalian ageing. Best Pract Res Clin Endocrinol Metabol 18:393–406
Richie JPJ, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA (1994) Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J 8:1302–1307
Riga D, Riga S (1995) Brain lipofuscinolysis and ceroidolysis – to be or not to be. Gerontology 41(Suppl 2)
Riga S, Riga D (1974) Effects of centrophenoxine on the lipofuscin pigments in the nervous system of old rats. Brain Res 72:265–275
Robert C, Spatz A, Faivre S, Armand J-P, Raymond E (2003) Tyrosine kinase inhibition and grey hair. The Lancet 361:1056
Roberts-Thomson I, Whittingham S, Youngschaiyd U, al e (1974) Aging, immune response and mortality. Lancet 2:368–370
Robertson OH (1961) Prolongation of the life span of Kokanee salmon (Oncorhynchus nerka kennerlyi) by castration before beginning of gonad development. Proc NY Acad Sci 47:609–621
Robertson OH, Hane S, Wexler BC, Rinfret AP (1963) The effect of hydrocortisone on immature rainbow trout (Salmo gairdnerii). General and Comparative Endocrinol 3:422–436
Robertson OH, Wexler BC (1960) Histological changes in the organs and tissues of senile castrated kokanee salmon: Oncorhynchus nerka kennerlyi. General and Comparative Endocrinol 2:458–472
Robertson OH, Wexler BC, Miller BF (1961) Degenerative changes in the cardiovascular system of the spawning Pacific salmon (Oncorhynchus tshawytscha). Circul Res 9:826–834
Robinson DS, Nies A, Davis JN et al. (1972) Ageing, monoamines, and monoamine oxidase levels. Lancet 1:290
Rogina B, Helfand SL, Frankel S (2002) Longevity regulation by Drosophila Rdp3 deacetylase and caloric restriction. Science 298:1745
Rosa A et al. (2007) Differential methylation of the X-chromosome is a possible source of discordance for bipolar disorder female monozygotic twins. Am J Med Genet B Neuropsychiatr Genet October 22nd
Rose MR (1991) The Evolutionary Biology of Aging. Oxford University Press, Oxford
Rose MR (2005) The Long Tomorrow, How Advances in Evolutionary Biology Can Help Us Postpone Aging. Oxford University Press, New York
Rose MR et al. (2010) Evolutionary nutrigenomics. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 357–366
Rose MR, Mueller LD (2000) Ageing and immortality. Philosophical Trans Royal Soc London Series B Biol Sci 355:1657–1662
Rose MR, Rauser CL, Mueller LD, Benford G (2006) A revolution for aging research. Biogerontology 7:269–277
Roth GS et al. (2002) Biomarkers of caloric restriction may predict longevity in humans. Science 297:811
Rothstein M (1979) The formation of altered enzymes in aging animals. Mech Ageing Dev 9:197–202
Roy D, Pathak DN, Singh R (1983) Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain. Exp Gerontol 18:185–197
Rudman D (1985) Growth hormone, body composition and aging. J Am Geriatr Soc 33:800–807
Rudman D, Feller AG, Cohn L, Shetty KR, Rudman IW, Draper MW (1991) effects of human growth hormone on body composition in elderly men. Hormone Res 36(Suppl. 1):73–81
Rudman D, Feller AG, Nagraj HS et al. (1990) Effect of human growth hormone in men over 60 years old. NE J Med 323:1–6
Ruehl WW, Entriken TL, Muggenburg BA, Bruyette DS, Griffith WC, Hahn FF (1997) Treatment with l-deprenyl prolongs life in elderly dogs. Life Sci 61:1037–1044
Rushton DH, Norris MJ, Dover R, Busuttil N (2002) Causes of hair loss and the developments in hair rejuvenation. Int J Cosmet Sci 24:17–23
Russell AP (2004) Lipotoxicity: the obese and endurance-trained paradox. Int J Obesity-Related Metabol Disorders 28:S66–S71
Ryu JW et al. (2003) DHEA administration increases brown fat uncoupling protein 1 levels in obese OLETF rats. Biochem Biophys Res Commun 303:726–731
Sahin E, DePinho RA (2010) Linking functional decline of telomeres, mitochondria and stem cells during aging. Nature 464:520–528
Salmon AB, Ljungman M, Miller RA (2008) Cells from long-lived mutants exhibit enhanced repair of ultraviolent lesions. J Gerontol A Biol Sci Med Sci 63:219–231
Sanz A, Caro P, Ayala V, Portero-Otin M, Pamplona R, Barja G (2006) Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins. FASEB J 20:1064–1073
Sarin KY, Artandi SE (2007) Aging, graying and loss of melanocyte stem cells. Stem Cell Rev 3:212–217
Sashital DG, Butcher SE (2006) Flipping off the riboswitch: RNA structures that control gene expression. ACS Chem Biol 21:341–345
Sat B, Reches M, Engelberg-Kulka H (2003) The Escherichia coli mazEF suicide module mediates thymineless death. J Bacteriol 185:1803–1807
Schaller GB (1972) The Serengeti Lion: A Study in Predator-Prey Relations. University of Chicago Press, Chicago
Schoenofen EA et al. (2006) Characteristics of 32 supercentenarians. J Am Geriatr Soc 54:1237–1240
Seehuus S-C, Norberg K, Gimsa U, Krekling T, Amdam GV (2006) Reproductive protein protects functionally sterile honey bee workers from oxidative stress. Proc Nat Acad Sci 103:962–967
Segall PE, Timiras PA (1976) Patho-physiologic findings after chronic tryptophan deficiency in rats: a model for delayed growth and aging. Mech Ageing Develop 5:109–124
Semkova I, Wolz P, Schilling M, Krieglstein J (1996) Selegiline enhances NGF synthesis and protects central nervous system neurons from excitotoxic and ischemic damage. Eur J Pharmacol 315:19–30
Seniuk NA, Henderson JT, Tatton WG, Roder JC (1994) Increased CNTF gene expression in process-bearing astrocytes following injury is augmented by R(-)-deprenyl. J Neurosci Res 37:278–286
Sethupathy P et al. (2007) Human microRNA-155 on chromosome 21 differentially interacts with its polymorphic target in the AGTR1 3' untranslated region: a mechanism for functional single-nucleotide polymorphisms related to phenotypes. Am J Human Genet 81:405–413
Sharma D, Maurya AK, Singh R (1993) Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine. Neurobiol Aging 14:319–330
Sharma HK, Rothstein M (1980) Altered enolase in aged Turbatrix aceti results from conformational changes in the enzyme. PNAS 77:5865–5868
Sharma S et al. (2004) Intramyocardial lipid accumulation in the failing human heart resembles the lipotoxic rat heart. FASEB J 18:1692–1700
Shaw RJ et al. (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310:1642–1646
Shay JW, Wright WE (2008) Telomeres and telomerase in aging and cancer. In: Guarente LP, Partridge L, Wallace DC (eds) Molecular Biology of Aging. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 575–597
Shikama N, Ackermann R, Brack C (1994) Protein synthesis elongation factor EF-1alpha expression and longevity in Drosophila melanogaster. Proc Nat Acad Sci 91:4199–4203
Sikes SK (1971) The Natural History of the African Elephant. American Elsevier, New York
Silber JR, Fry M, Martin GM et al. (1985) Fidelity of DNA polymerases isolated from regenerating liver chromatin of aging Mus musculus. J Biol Chem 260:1304–1310
Silber SJ et al. (2008) A series of monozygotic twins discordant for ovarian failure: ovary transplantation (cortical versus microvascular) and cryopreservation. Human Reprod 23:1531–1537
Simon AF, Shih C, Mack A, Benzer S (2003) Steroid control of longevity in Drosophila melanogaster. Science 299:1407–1410
Simpson JG, Gray ES, Michie W, Beck JS (1975) The influence of preoperative drug treatment on the extent of hyperplasia of the thymus in primary thyrotoxicosis. Clin Exp Immunol 22:249–255
Singh R, Mukherjee B (1972) Some observations on the lipofuscin of the avian brain with a review of some rarely considered findings concerning the metabolic and physiologic significance of the neuronal lipofuscin. Acta Ana. (Basel) 83:302–320
Smigrodzki R, Portell FR (2010) Mitochondrial manipulation as a treatment for aging. In: Fahy GM, West M, Coles SL, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 521–541
Smith ML, Bruhn JN, Anderson JB (1992) The fungus Armillaria bulbosa is among the largest and oldest living organisms. Nature 356:428–431
Soderstrom TR, Calderon CE (1979) A commentary on the bamboos (Poaceae: Bambusoideae). Biotropica 11:161–172
Sojar HT, Rothstein M (1986) Protein synthesis by liver ribosomes from aged rats. Mech Ageing Develop 35:47–57
Sonntag WE, Forman LJ, Miki N, Trapp JM, Gottschall PE, Meites J (1982) L-dopa restores amplitude of growth hormone in old male rats to that observed in young male rats. Neuroendocrinology 34:163–168
Sonntag WE, Hylka VW, Meites J (1985) Growth hormone restores protein synthesis in skeletal muscle of old male rats. J Gerontol 40:689–694
Sonntag WE, Meites J (1988) Decline in GH secretion in aging animals and man. In: Everitt AV, Walton JR (eds) Regulation of Neuroendocrine Aging. Karger, Basel, pp. 111–124
Speakman JR et al. (2004) Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer. Aging Cell 3:87–95
Spees JL, Olson SD, Whitney MJ, Prockop DJ (2006) Mitochondrial transfer between cells can rescue aerobic respiration. Proc Nat Acad Sci 103:1283–1288
Spindler SR (2001) Calorie restriction enhances the expression of key metabolic enzymes associated with protein renewal during aging. Annals NY Acad Sci 928:296–304
Spindler SR (2005) Rapid and reversible induction of the longevity, anticancer and genomic effects of caloric restriction. Mech Ageing Develop 126:960–966
Spindler SR (2010) Biological effects of calorie restriction: implications for modification of human aging. In: Fahy Gm, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 367–438
Spindler SR, Dhahbi JM (2007) Conserved and tissue-specific genic and physiologic responses to caloric restriction and altered IGF1 signaling in mitotic and postmitotic tissues. Annu Rev Nutr 27:193–217
Spindler SR, Mote PL (2007) Screening candidate longevity therapeutics using gene-expression arrays. Gerontology 53:306–321
Spoerri PE, Glees P (1974) The effects of dimethylaminoethyl p-chlorophenoxyacetate on spinal ganglia neurons and satellite cells in culture. Mitochondrial changes in he aging neurons. An electron microscope study. Mech Ageing Develop 3:131–155
Spoerri PE, Glees P (1975) The mode of lipofuscin removal from hypothalamic neurons. Exp Gerontol 10:225–228
Spoerri PE, Glees P, Ghazzawi E (1974) Accumulation of lipofuscin in the myocardium of senile guinea pigs: dissolution and removal of lipofuscin following dimethylaminoethyl p-chlorophenoxyacetate administration. An electron microscopic study. Mech Ageing Develop 3:311–321
Srebro Z (1966) Lipofuscin turnover in the frog brain. Naturwissenschaften 53:590
Srivastava VK, Busbee DL (1992) Decreased fidelity of DNA polymerases and decreased DNA excision repair in aging mice: effects of caloric restriction. Biochem Biophys Res Commun 31
Srivastava VK, Tilley RD, Miller S, Hart R, Busbee D (1991) Effects of aging and dietary restriction on DNA polymerase expression in mice. Exp Gerontol 26:97–112
Stancheva SL, Alova LG (1988) Effect of centrophenoxine, piracetam and aniracetam on the monoamine oxidase activity in different brain structures of rats. Farmakol Toksikol 51:16–18
Staton BA, Mixon RL, Dharia S, Brissie RM, Parker CR Jr (2004) Is reduced cell size the mechanism for shrinkage of the adrenal zona reticularis in aging? Endocrinol Res 30:529–534
Steer CJ, Kren BT (2010) Reversing age-related DNA damage through engineered DNA repair. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, p
Steffen KK et al. (2008) Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell 133:292–302
Stoll S, Hafner U, Kranzlin B, Muller WE (1997) Chronic treatment of Syrian hamsters with low-dose selegiline increases life span in females but not males. Neurobiol Aging 18:205–211
Stough D et al. (2005) Psychological effect, pathophysiology, and management of androgenetic alopecia in men. Mayo Clin Proc 80:1316–1322
Strathmann MF, Strathmann RR (2007) An extraordinarily long larval duration of 4.5 years from hatching to metamorphosis for teleplanic veligers of Fusitriton oregonensis. Biol Bull 213:152–159
Straub RH et al. (1998) Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metabol 83:2012–2017
Stuchlikova E, Juricova-Horakova M, Deyl Z (1975) New aspects of the dietary effect of life prolongation in rodents. What is the role of obesity in aging? Exp Gerontol 10:141–144
Suh Y et al. (2008) Functionally significant insulin-like growth factor 1 receptor mutations in centenarians. Proc Nat Acad Sci 105:3438–3442
Sylvia V, Curtin G, Norman J, Stec J, Busbee D (1988) Activation of a low specific activity form of DNA polymerase alpha by inositol-1,4-bisphosphate. Cell 54:651–658
Syntichaki P, Tavernarakis N (2006) Signalling pathways regulating protein synthesis during ageing. Exp Gerontol 41:1020–1025
Syntichaki P, Troulinaki K, Tavernarakis N (2007) eIF4E function in somatic cells modulates ageing in Caenorhabditis elegans. Nature 445:922–926
Tani F, Miyoshi K (1977) Neuronal lipofuscin in centrophenoxine treated rats. Folia Psychiatr Neurol Jpn 31:104–109
Tatar M (2004) The neuroendocrine regulation of Drosophila aging. Exp Gerontol 39:1745–1750
Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351
Tatar M, Kopelman A, Epstein D, Tu MP, Yin CM, Garofalo RS (2001a) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function. Science 292:107–110
Tatar M, Priest N, Chien S (2001b) Negligible senescence during reproductive diapause in D. melanogaster. Am Naturalist 158:248–258
Terry D et al. (2004) Lower all-cause, cardiovascular, and cancer mortality in centenarians’ offspring. J Am Geriatr Soc 52:2074–2076
ThyagaRajan S, Felten DL (2002) Modulation of neuroendocrine-immune signaling by L-deprenyl and L-desmethyldeprenyl in aging and mammary cancer. Mech Ageing Develop 123:1065–1079
ThyagaRajan S, Felten SY, Felten DL (1998a) Anti-tumor effect of L-deprenyl in rats with carcinogen-induced mammary tumors. Cancer Lett 123:177–183
ThyagaRajan S, Madden KS, Kalvass JC, Dimitrova S, Felten SY, Felten DL (1998b) L-deprenyl-induced increase in IL-2 and NK cell activity accompanies restoration of noradrenergic nerve fibers in the spleens of old F344 rats. J Neuroimmunol 92:9–21
ThyagaRajan S, Madden KS, Stevens SY, Felten DL (2000) Anti-tumor effect of L-deprenyl is associated with enhanced central and peripheral neurotransmission and immune function in rats with carcinogen-induced mammary tumors. J Neuroimmunol 109:95–104
ThyagaRajan S, Meites J, Quadri SK (1995) Deprenyl reinitiates estrous cycles, reduces serum prolactin, and decreases the incidence of mammary and pituitary tumors in old acyclic rats. Endocrinology 136:1103–1110
Tobin DJ, Paus R (2001) Graying: gerontobiology of the hair follicle pigmentary unit. Exp Gerontol 36:29–54
Tomas-Loba A et al. (2008) Telomerase reverse transcriptase delays aging in cancer-resistant mice. Cell 135:609–622
Tran H et al. (2002) DNA repair pathway stimulated by the forkhead transcription factor FOXO3a through the Gadd45 protein. Science 296:530–534
Trifunovic A et al. (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Nat Acad Sci 102:17993–17998
Trifunovic A et al. (2004) Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 429:417–423
Trinei M et al. (2002) A p53-p66Shc signaling pathway controls intracellular redox status, levels of oxidation-damaged DNA and oxidative stress-induced apoptosis. Oncogene 21:3872–3878
Tsai WB, Chung YM, Takahashi Y, Xu Z, Hu MC (2008) Functional interaction between FOXO3a and ATM regulates DNA damage response. Nature Cell Biol 10:460–467
Tsuchiya T, Dhahbi JM, Cui X, Mote PL, Bartke A, Spindler SR (2004) Additive regulation of hepatic gene expression by dwarfism and caloric restriction. Physiol Genomics 17:307–315
Tu MP, Epstein D, Tatar M (2002) The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homologue chico. Aging Cell 1:75–80
Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296–300
Van Remmen H et al. (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16:29–37
Vargas R, Castaneda M (1981) Role of elongation factor 1 in the translational control of rodent brain protein synthesis. J Neurochem 37:687–694
Vaupel JW et al. (1998) Biodemographic trajectories of longevity. Science 280:855–860
Vaupel JW (2010) Biodemography of human aging. Nature 464:536–542
Ventruti A, Cuervo AM (2007) Autophagy and neurodegeneration. Curr Neurol Neurosci Rep 7:443–451
Vermulst M et al. (2007) Mitochondrial point mutations do not limit the natural lifespan of mice. Nat Genet 39:540–543
Villareal DT, Holloszy JO (2006) DHEA enhances effects of weight training on muscle mass and strength in elderly men and women. Am J Physiol Endocrinol Metabol 291
von Holst D, Hutzelmeyer H, Kaetzke P, Khaschel M, Schonheiter R (1999) Social rank, stress, fitness, and life expectancy in wild rabbits. Naturwissenschaften 86:388–393
Walker RF, Pakula LC, Sutcliffe MJ, Kruk PA, Graakjaer J, Shay JW (2009) A case study of “disorganized development” and its possible relevance to genetic determinants of aging. Mech Ageing Develop 130:350–356
Wang E (2007) MicroRNA, the putative molecular control for mid-life decline. Ageing Res Rev 6:1–11
Wang MC, Bohmann D, Jasper H (2005) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121:115–125
Wang Y et al. (2001) Muscle-specific mutations accumulate with aging in critical human mtDNA control sites for replication. Proc Nat Acad Sci 98:4022–4027
Wang YX et al. (2004) Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2:e294
Webster GC (1985) Protein synthesis in aging organisms. In: Sohall RS, Birnbaum LS, Cutler RG (eds) Molecular Biology of Aging: Gene Stability and Gene Expression. Raven Press, New York, pp. 263–289
Webster GC (1988) Protein synthesis. In: Lints FA, Soliman MH (eds) Drosophila as a Model Organism for Ageing Studies. Blackie, London, pp. 119–128
Webster GC, Webster SL (1982) Effects of age on the post-initiation stages of protein synthesis. Mech Ageing Develop 18:369–378
Webster GC, Webster SL (1984) Specific disappearance of translatable messenger RNA for elongation factor one in aging Drosophila melanogaster. Mech Ageing Develop 24:335–342
Weindruch R, Colman RJ, Perez V, Richardson AG (2008) How does caloric restriction increase the longevity of mammals? In: Guarente LP, Partridge L, Wallace DC (eds) Molecular Biology of Aging. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp. 409–425
Weraarchakul N, Strong R, Wood WG, Richardson A (1989) The effect of aging and dietary restriction on DNA repair. Exp Cell Res 181:197–204
West M (2010) Embryonic stem cells: prospects of regenerative medicine for the treatment of human aging. In: Fahy GM, West M, Coles LS, Harris SB (eds) The Future of Aging: Pathways to Human Life Extension. Springer, Berlin, Heidelberg, New York, pp. 451–487
Wherry ET (1972) Box-huckleberry as the oldest living protoplasm. Castanea 37:94–95
Wikby A et al. (2006) The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Develop 127:695–704
Williams GC (1957) Pleiotropy, natural selection, and the evolution of senescence. Evolution 11:398–411
Wilson DM, III, McNeil DR (2007) Base excision repair and the central nervous system. Neuroscience 145:1187–1200
Wilson EO (1971) The Insect Societies. Belknap Press, Cambridge
Winston ML (1987) The Biology of the Honey Bee. Harvard University Press, Cambridge, MA
Wodinsky J (1977) Hormonal inhibition of feeding and death in octopus: control by optic gland secretion. Science 198:948–951
Wodsedalek JE (1917) Five years of starvation of larvae. Science 46:366–367
Wolkow CA (2002) Life span: getting the signal from the nervous system. Trends Neurosci 25:212–216
Wood JG et al. (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689
Wood PL, Peloquin A (1982) Increases in choline levels in rat brain elicited by meclofenoxate. Neuropharmacology 21:349–354
Woolf TM (1998) Therapeutic repair of mutated nucleic acid sequences. Nature Biotechnology 16:341–344
Woolley P (1971) Differential mortality of Antechinus stuartii (Macleay): nitrogen balance of somatic changes. Aust J Zool 19:347–353
Woolley P (1981) Antechinus bellus, another dasyurid marsupial with post-mating mortality of males. J Mammal 62:381–382
Wu D, Rea SL, Yashin AI, Johnson T (2006) Visualizing hidden heterogeneity in isogenic populations of C. elegans. Exp Gerontol 41:261–270
Xi G, Shen X, Clemmons DR (2008) p66shc negatively regulates insulin-like growth factor 1 signal transduction via inhibition of p52she binding to Src homology 2 domain-containing protein tyrosine phosphatase substrate-1 leading to impaired growth factor receptor-bound protein-2 membrance recruitment. Mol Endocrinol 22:2162–2175
Yamada Y, Ando F, Niino N, Shimokata H (2005) Association of polymorphisms of the androgen receptor and klotho genes with bone mineral density in Japanese women. J Mol Med 83:50–57
Yamamoto M et al. (2005) Regulation of oxidative stress by the anti-aging hormone Klotho. J Biol Chem 280:38029–38034
Yen TT, Knoll J (1992) Extension of lifespan in mice treated with Dinh lang (Policias fruticosum L.) and (-)deprenyl. Acta Physiol Hung 79:119–124
Young VR, Steffee WP, Pencharz PB, Winterer JG, Scrimshaw NW (1975) Total human body protein synthesis in relation to protein requirements at various ages. Nature 253:192–194
Zaratiegui M, Irvine DV, Martienssen RA (2007) Noncoding RNAs and gene silencing. Cell 128:763–776
Zeng YC et al. (1995) Effect of long-term treatment with L-deprenyl on the age-dependent microanatomical changes in the rat hippocampus. Mech Ageing Develop 79:169–185
Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14:959–965
Zihlman AL, Morbeck ME, Sumner DR (1989) Tales of Gombe chimps as told in their bones. Anthroquest (Leakey Foundation News) No. 40 (Summer):20–22
Zs-Nagy I (1989) On the role of intracellular physicochemistry in quantitative gene expression during aging and the effect of centrophenoxine. A review. Arch Gerontol Geriatr 9:215–229
Zs-Nagy I, Semsei I (1984) Centrophenoxine increases the rates of total and mRNA synthesis in the brain cortex of old rats: an explanation of its action in terms of the membrane hypothesis of aging. Exp Gerontol 19:171–178
Zuckerman BM, Barrett KA (1978) Effects of PCA and DMAE on the namatode [sic] Caenorhabditis briggsae. Exp Aging Res 4:133–139
Acknowledgements
I thank J. Mitteldorf for helpful peer review of this chapter and Don Gennery for providing Fig. 6.3. I thank S. Spindler, S. Mullen, and K. Perrott for gracious assistance in obtaining obscure or elusive source material.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Fahy, G.M. (2010). Precedents for the Biological Control of Aging: Experimental Postponement, Prevention, and Reversal of Aging Processes. In: Fahy, G.M., West, M.D., Coles, L.S., Harris, S.B. (eds) The Future of Aging. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-3999-6_6
Download citation
DOI: https://doi.org/10.1007/978-90-481-3999-6_6
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-3998-9
Online ISBN: 978-90-481-3999-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)