Abstract
Chronic stress [i.e. long-term elevation of glucocorticoid (GC) levels] and aging have similar, negative effects on the functioning of an organism. Aged individuals’ declining ability to regulate GC levels may therefore impair their ability to cope with stress, as found in humans. The coping of aged animals with long-term natural stressors is virtually unstudied, even though the ability to respond appropriately to stressors is likely integral to the reproduction and survival of wild animals. To assess the effect of age on coping with naturally fluctuating energetic demands, we measured stress hormone output via GC metabolites in faecal samples (fGCM) of wild grey mouse lemurs (Microcebus murinus) in different ecological seasons. Aged individuals were expected to exhibit elevated fGCM levels under energetically demanding conditions. In line with this prediction, we found a positive age effect in the dry season, when food and water availability are low and mating takes place, suggesting impaired coping of aged wild animals. The age effect was significantly stronger in females, the longer-lived sex. Body mass of males but not females correlated positively with fGCM in the dry season. Age or body mass did not influence fGCM significantly in the rainy season. The sex- and season-specific predictors of fGCM may reflect the differential investment of males and females into reproduction and longevity. A review of prior research indicates contradictory aging patterns in GC regulation across and even within species. The context of sampling may influence the likelihood of detecting senescent declines in GC functioning.
Similar content being viewed by others
References
Alberts S, Archie E, Gesquiere L, Altmann J, Christensen K (2014) The male-female health-survival paradox: a comparative perspective on sex differences in aging and mortality. In: Weinstein M, Lane MA (eds) Sociality, hierarchy, health: comparative biodemography. National Academies Press, Washington, pp 337–361
Angelier F, Shaffer SA, Weimerskirch H, Chastel O (2006) Effect of age, breeding experience and senescence on corticosterone and prolactin levels in a long-lived seabird: the wandering albatross. Gen Comp Endocrinol 149:1–9
Angelier F, Moe B, Weimerskirch H, Chastel O (2007a) Age-specific reproductive success in a long-lived bird: do older parents resist stress better? J Anim Ecol 76:1181–1191
Angelier F, Weimerskirch H, Dano S, Chastel O (2007b) Age, experience and reproductive performance in a long-lived bird: a hormonal perspective. Behav Ecol Sociobiol 61:611–621
Barton K (2014) MuMIn: multi-model inference. R package version 1.10.0. http://CRAN.R-project.org/package=MuMIn
Bates DM, M, Bolker B, Walker S (2014) lme4: linear mixed-effects models using Eigen and S4. R package version 1.1-7, http://CRAN.R-project.org/package=lme4
Beehner JC, McCann C (2008) Seasonal and altitudinal effects on glucocorticoid metabolites in a wild primate (Theropithecus gelada). Phys Behav 95:508–514. doi:10.1016/j.physbeh.2008.07.022
Bokony V, Lendvai AZ, Liker A, Angelier F, Wingfield JC, Chastel O (2009) Stress response and the value of reproduction: are birds prudent parents? Am Nat 173:589–598
Bonduriansky R, Maklakov A, Zajitschek F, Brooks R (2008) Sexual selection, sexual conflict and the evolution of ageing and life span. Funct Ecol 22:443–453
Bonier F, Martin PR, Moore IT, Wingfield JC (2009a) Do baseline glucocorticoids predict fitness? Trends Ecol Evol 24:634–642
Bonier F, Moore IT, Martin PR, Robertson RJ (2009b) The relationship between fitness and baseline glucocorticoids in a passerine bird. Gen Comp Endocrinol 163:208–213
Boonstra R (2005) Equipped for life: the adaptive role of the stress axis in male mammals. J Mammal 86:236–247. doi:10.1644/BHE-001.1
Boonstra R (2013) Reality as the leading cause of stress: rethinking the impact of chronic stress in nature. Funct Ecol 27:11–23. doi:10.1111/1365-2435.12008
Boonstra R, McColl CJ, Karels TJ (2001) Reproduction at all costs: the adaptive stress response of male Arctic ground squirrels. Ecology 82:1930–1946. doi:10.1890/0012-9658(2001)082[1930:RAACTA]2.0.CO;2
Boonstra R, Dantzer B, Delehanty B, Fletcher QE, Sheriff MJ (2014) Equipped for life in the boreal forest: the role of the stress axis in mammals. ARCTIC 67:82–97. doi:10.14430/arctic4357
Brett LP, Chong GS, Coyle S, Levine S (1983) The pituitary-adrenal response to novel stimulation and ether stress in young adult and aged rats. Neurobiol Aging 4:133–138
Cabezas S, Blas J, Marchant TA, Moreno S (2007) Physiological stress levels predict survival probabilities in wild rabbits. Horm Behav 51:313–320. doi:10.1016/j.yhbeh.2006.11.004
Clinchy M, Sheriff MJ, Zanette LY (2013) Predator-induced stress and the ecology of fear. Funct Ecol 27:56–65. doi:10.1111/1365-2435.12007
Crespi EJ, Williams TD, Jessop TS, Delehanty B (2013) Life history and the ecology of stress: how do glucocorticoid hormones influence life-history variation in animals? Funct Ecol 27:93–106. doi:10.1111/1365-2435.12009
Critchlow V, Liebelt R, Bar-Sela M, Mountcastle W, Lipscomb H (1963) Sex difference in resting pituitary-adrenal function in the rat. Am J Physiol 205:807–815
Dammhahn M, Kappeler PM (2008) Comparative Feeding Ecology of Sympatric Microcebus berthae and M. murinus. Int J Primatol 29:1567–1589. doi:10.1007/s10764-008-9312-3
Eberle M, Kappeler PM (2002) Mouse lemurs in space and time: a test of the socioecological model. Behav Ecol Sociobiol 51:131–139. doi:10.1007/s002650100409
Eberle M, Kappeler PM (2004a) Selected polyandry: female choice and inter-sexual conflict in a small nocturnal solitary primate (Microcebus murinus). Behav Ecol Sociobiol 57:91–100. doi:10.1007/s00265-004-0823-4
Eberle M, Kappeler PM (2004b) Sex in the dark: determinants and consequences of mixed male mating tactics in Microcebus murinus, a small solitary nocturnal primate. Behav Ecol Sociobiol 57:77–90. doi:10.1007/s00265-004-0826-1
Elliott KH, O’Reilly KM, Hatch SA, Gaston AJ, Hare JF, Anderson WG (2014) The prudent parent meets old age: A high stress response in very old seabirds supports the terminal restraint hypothesis. Horm Behav 66:828–837. doi:10.1016/j.yhbeh.2014.11.001
Frolkis VV (1993) Stress-age syndrome. Mech Ageing Dev 69:93–107
Ganswindt A, Palme R, Heistermann M, Borragan S, Hodges JK (2003) Non-invasive assessment of adrenocortical function in the male African elephant (Loxodonta africana) and its relation to musth. Gen Comp Endocrinol 134:156–166
George SC, Smith TE, Mac Cana PSS, Coleman R, Montgomery WI (2014) Physiological stress in the Eurasian badger (Meles meles): effects of host, disease and environment. Gen Comp Endocrinol 200:54–60. doi:10.1016/j.ygcen.2014.02.017
Gesquiere LR et al (2008) Coping with a challenging environment: effects of seasonal variability and reproductive status on glucocorticoid concentrations of female baboons (Papio cynocephalus). Horm Behav 54:410–416
Gesquiere LR, Onyango PO, Alberts SC, Altmann J (2011) Endocrinology of year-round reproduction in a highly seasonal habitat: environmental variability in testosterone and glucocorticoids in baboon males. Am J Phys Anthropol 144:169–176. doi:10.1002/ajpa.21374
Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5:243–251
Goncharova ND, Lapin BA (2002) Effects of aging on hypothalamic-pituitary-adrenal system function in non-human primates. Mech Ageing Dev 123:1191–1201
Goncharova ND, Lapin BA (2004) Age-related endocrine dysfunction in nonhuman primates. Ann NY Acad Sci 1019:321–325
Goodman SM, O’Connor S, Langrand O (1993) A review of predation on lemurs: implications for the evolution of social behavior in small, nocturnal primates. In: Kappeler PM, Ganzhorn JU (eds) Lemur social systems and their ecological basis. Springer, Berlin, pp 51–66
Goutte A, Antoine É, Weimerskirch H, Chastel O (2010) Age and the timing of breeding in a long-lived bird: a role for stress hormones? Funct Ecol 24:1007–1016. doi:10.1111/j.1365-2435.2010.01712.x
Graham J, Christian L, Kiecolt-Glaser J (2006) Stress, age, and immune function: toward a lifespan approach. J Behav Med 29:389–400. doi:10.1007/s10865-006-9057-4
Gust D, Wilson M, Stocker T, Conrad S, Plotsky P, Gordon T (2000) Activity of the hypothalamic-pituitary-adrenal axis is altered by aging and exposure to social stress in female rhesus monkeys 1. J Clin Endcrinol Metab 85:2556–2563
Hämäläinen A, Dammhahn M, Aujard F, Eberle M, Hardy I, Kappeler PM, Perret M, Schliehe-Diecks S, Kraus C (2014a) Senescence or selective disappearance? Age trajectories of body mass in wild and captive populations of a small-bodied primate. Proc R Soc B Biol Sci 281:20140830. doi:10.1098/rspb.2014.0830
Hämäläinen A, Heistermann M, Fenosoa ZSE, Kraus C (2014) Evaluating capture stress in wild gray mouse lemurs via repeated fecal sampling: method validation and the influence of prior experience and handling protocols on stress responses. Gen Comp Endocrinol 195:68–79. doi:10.1016/j.ygcen.2013.10.017
Hämäläinen A, Dammhahn M, Aujard F, Kraus C (2015) Losing grip: senescent decline in physical strength in a small-bodied primate in captivity and in the wild. Exp Gerontol 61:54–61. doi:10.1016/j.exger.2014.11.017
Handa RJ, Burgess LH, Kerr JE, O’Keefe JA (1994) Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis. Horm Behav 28:464–476. doi:10.1006/hbeh.1994.1044
Harris BN (2012) Reproduction in the face of stress: mediation by the hypothalamic-pituitary-adrenal (HPA) axis. PhD dissertation, UC Riverside
Harris BN, Saltzman W (2013) Effects of aging on hypothalamic-pituitary-adrenal (HPA) axis activity and reactivity in virgin male and female California mice (Peromyscus californicus). Gen Comp Endocrinol 186:41–49. doi:10.1016/j.ygcen.2013.02.010
Hau M, Ricklefs RE, Wikelski M, Lee KA, Brawn JD (2010) Corticosterone, testosterone and life-history strategies of birds. Proc Biol Sci 277:3203–3212. doi:10.1098/rspb.2010.0673
Heidinger BJ, Nisbet ICT, Ketterson ED (2006) Older parents are less responsive to a stressor in a long-lived seabird: a mechanism for increased reproductive performance with age? Proc R Soc B Biol Sci 273:2227–2231. doi:10.1098/rspb.2006.3557
Heidinger BJ, Nisbet ICT, Ketterson ED (2008) Changes in adrenal capacity contribute to a decline in the stress response with age in a long-lived seabird. Gen Comp Endocrinol 156:564–568. doi:10.1016/j.ygcen.2008.02.014
Heistermann M, Ademmer C, Kaumanns W (2004) Ovarian cycle and effect of social changes on adrenal and ovarian function in Pygathrix nemaeus. Int J Primatol 25:689–708. doi:10.1023/B:IJOP.0000023581.17889.0f
Herman JP, Larson BR, Speert DB, Seasholtz AF (2001) Hypothalamo–pituitary–adrenocortical dysregulation in aging F344/Brown-Norway F1 hybrid rats. Neurobiol Aging 22:323–332
Heuser I, Gotthardt U, Schweiger U, Schmider J, Lammers CH, Dettling M, Holsboer F (1994) Age-associated changes of pituitary-adrenocortical hormone regulation in humans: importance of gender. Neurobiol Aging 15:227–231
Juster R-P, McEwen BS, Lupien SJ (2010) Allostatic load biomarkers of chronic stress and impact on health and cognition. Neurosc Biobehav Rev 35:2–16
Kasckow JW et al (2005) Stability of neuroendocrine and behavioral responsiveness in aging Fischer 344/Brown-Norway hybrid rats. Endocrinology 146:3105–3112
Kitay JI (1961) Sex differences in adrenal cortical secretion in the rat. Endocrinology 68:818–824
Kitaysky AS, Wingfield JC, Piatt JF (1999) Dynamics of food availability, body condition and physiological stress response in breeding Black-legged Kittiwakes. Funct Ecol 13:577–584. doi:10.1046/j.1365-2435.1999.00352.x
Koolhaas J et al (2011) Stress revisited: a critical evaluation of the stress concept. Neurosc Biobehav Rev 35:1291–1301
Kraus C, Eberle M, Kappeler PM (2008) The costs of risky male behaviour: sex differences in seasonal survival in a small sexually monomorphic primate. Proc R Soc B Biol Sci 275:1635–1644. doi:10.1098/rspb.2008.0200
Kudielka BM, Kirschbaum C (2005) Sex differences in HPA axis responses to stress: a review. Biol Psychol 69:113–132
Kudielka BM, Hellhammer DH, Wüst S (2009) Why do we respond so differently? Reviewing determinants of human salivary cortisol responses to challenge. Psychoneuroendocrinology 34:2–18. doi:10.1016/j.psyneuen.2008.10.004
Kuznetsova A, Brockhoff PB, Christensen RHB (2014) lmerTest: tests for random and fixed effects for linear mixed effect models (lmer objects of lme4 package), 2.0-6 edn.http://www.cran.r-project.org/web/packages/lmerTest/lmerTest.pdf
Landys MM, Ramenofsky M, Wingfield JC (2006) Actions of glucocorticoids at a seasonal baseline as compared to stress-related levels in the regulation of periodic life processes. Gen Comp Endocrinol 148:132–149
Languille S et al (2012) The grey mouse lemur: a non-human primate model for ageing studies. Ageing Res Rev 11:150–162
Lecomte VJ et al (2010) Patterns of aging in the long-lived wandering albatross. Proc Natl Acad Sci USA 107:6370–6375
Massot M, Clobert J, Montes-Poloni L, Haussy C, Cubo J, Meylan S (2011) An integrative study of ageing in a wild population of common lizards. Funct Ecol 25:848–858. doi:10.1111/j.1365-2435.2011.01837.x
McEwen BS (1998) Protective and damaging effects of stress mediators. New Engl J Med 338:171–179. doi:10.1056/NEJM199801153380307
McEwen BS (2008) Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 583:174–185. doi:10.1016/j.ejphar.2007.11.071
McEwen BS, Wingfield JC (2003) The concept of allostasis in biology and biomedicine. Horm Behav 43:2–15
Mizoguchi K, Ikeda R, Shoji H, Tanaka Y, Maruyama W, Tabira T (2009) Aging attenuates glucocorticoid negative feedback in rat brain. Neuroscience 159:259–270
Montiglio PO, Garant D, Pelletier F, Réale D (2014) Intra-individual variability in fecal cortisol metabolites varies with lifetime exploration and reproductive life history in eastern chipmunks (Tamias striatus). Behav Ecol Sociobiol 69:1–11. doi:10.1007/s00265-014-1812-x
Nakagawa S, Schielzeth H (2013) A general and simple method for obtaining R2 from generalized linear mixed-effects models. Methods Ecol Evol 4:133–142
Némoz-Bertholet F, Aujard F (2003) Physical activity and balance performance as a function of age in a prosimian primate (Microcebus murinus). Exp Gerontol 38:407–414
Nicolson N, Storms C, Ponds R, Sulon J (1997) Salivary cortisol levels and stress reactivity in human aging. J Gerontol A Biol Sci Med Sci 52:M68–M75
Nussey DH, Coulson T, Festa-Bianchet M, Gaillard JM (2008) Measuring senescence in wild animal populations: towards a longitudinal approach. Funct Ecol 22:393–406. doi:10.1111/j.1365-2435.2008.01408.x
Nussey DH et al (2011) Patterns of body mass senescence and selective disappearance differ among three species of free-living ungulates. Ecology 92:1936–1947. doi:10.1890/11-0308.1
Otte C, Hart S, Neylan TC, Marmar CR, Yaffe K, Mohr DC (2005) A meta-analysis of cortisol response to challenge in human aging: importance of gender. Psychoneuroendocrinology 30:80–91. doi:10.1016/j.psyneuen.2004.06.002
Patterson SH, Hahn TP, Cornelius JM, Breuner CW (2014) Natural selection and glucocorticoid physiology. J Evol Biol 27:259–274. doi:10.1111/jeb.12286
Perret M, Aujard F (2001) Regulation by photoperiod of seasonal changes in body mass and reproductive function in gray mouse lemurs (Microcebus murinus): differential responses by sex. Int J Primatol 22:5–24
Pinheiro JC, Bates DM (2000) Mixed effects models in S and S-PLUS. Springer, Berlin
Pride RE (2005) High faecal glucocorticoid levels predict mortality in ring-tailed lemurs (Lemur catta). Biol Lett 1:60–63
R Development Core Team (2014) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna URL: http://www.r-project.org
Reul JMHM, Rothuizen J, de Kloet ER (1991) Age-related changes in the dog hypothalamic-pituitary-adrenocortical system: neuroendocrine activity and corticosteroid receptors. J Steroid Biochem Mol Biol 40:63–69. doi:10.1016/0960-0760(91)90168-5
Ricklefs RE, Wikelski M (2002) The physiology/life-history nexus. Trends Ecol Evol 17:462–468
Romero LM (2002) Seasonal changes in plasma glucocorticoid concentrations in free-living vertebrates. Gen Comp Endocrinol 128:1–24
Rothuizen J, Reul J, Van Sluijs F, Mol J, Rijnberk A, de Kloet Ed (1993) Increased neuroendocrine reactivity and decreased brain mineralocorticoid receptor-binding capacity in aged dogs. Endocrinology 132:161–168
Sapolsky RM (1992) Do glucocorticoid concentrations rise with age in the rat? Neurobiol aging 13:171–174. doi:10.1016/0197-4580(92)90025-S
Sapolsky RM, Altmann J (1991) Incidence of hypercortisolism and dexamethasone resistance increases with age among wild baboons. Biol Psychiatry 30:1008–1016
Sapolsky RM, Krey LC, McEwen BS (1983) The adrenocorticol stress-response in the aged male rat: Impairment of recovery from stress. Exp Gerontol 18:55–64. doi:10.1016/0531-5565(83)90051-7
Sapolsky RM, Krey LC, McEwen BS (1984) Glucocorticoid-sensitive hippocampal neurons are involved in terminating the adrenocortical stress response. Proc Natl Acad Sci USA 81:6174–6177
Sapolsky RM, Krey LC, McEwen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7:284–301. doi:10.1210/edrv-7-3-284
Sapolsky R, Armanini M, Packan D, Tombaugh G (1987) Stress and glucocorticoids in aging. Endocrinol Metab Clin North Am 16:965–980
Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89. doi:10.1210/er.21.1.55
Schielzeth H (2010) Simple means to improve the interpretability of regression coefficients. Methods Ecol Evol 1:103–113
Schmid J (1999) Sex-specific differences in activity patterns and fattening in the gray mouse lemur (Microcebus murinus) in Madagascar. J Mammal 80:749–757
Schmid J, Kappeler PM (1998) Fluctuating sexual dimorphism and differential hibernation by sex in a primate, the gray mouse lemur (Microcebus murinus). Behav Ecol Sociobiol 43:125–132
Sheriff MJ, Krebs CJ, Boonstra R (2009) The sensitive hare: sublethal effects of predator stress on reproduction in snowshoe hares. J Anim Ecol 78:1249–1258
Sheriff M, Dantzer B, Delehanty B, Palme R, Boonstra R (2011) Measuring stress in wildlife: techniques for quantifying glucocorticoids. Oecologia 166:869–887. doi:10.1007/s00442-011-1943-y
Shoji H, Mizoguchi K (2010) Acute and repeated stress differentially regulates behavioral, endocrine, neural parameters relevant to emotional and stress response in young and aged rats. Behav Brain Res 211:169–177. doi:10.1016/j.bbr.2010.03.025
Touma C et al (2004) Age-and sex-dependent development of adrenocortical hyperactivity in a transgenic mouse model of Alzheimer’s disease. Neurobiol Aging 25:893–904
Van Kampen M, Fuchs E (1998) Age-related levels of urinary free cortisol in the tree shrew. Neurobiol Aging 19:363–366
Veldhuis JD, Sharma A, Roelfsema F (2013) Age-dependent and gender-dependent regulation of hypothalamic–adrenocorticotropic–adrenal axis. Endocrinol Metab Clin North Am 42:201–225. doi:10.1016/j.ecl.2013.02.002
Wilcoxen T, Boughton R, Schoech S (2010) Older can be better: physiological costs of paternal investment in the Florida scrub-jay. Behav Ecol Sociobiol 64:1527–1535. doi:10.1007/s00265-010-0966-4
Wilcoxen TE, Boughton RK, Bridge ES, Rensel MA, Schoech SJ (2011) Age-related differences in baseline and stress-induced corticosterone in Florida scrub-jays. Gen Comp Endocrinol 173:461–466
Wilkinson CW, Peskind ER, Raskind MA (1997) Decreased hypothalamic–pituitary adrenal axis sensitivity to cortisol feedback inhibition in human aging. Neuroendocrinology 65:79–90
Williams GC (1957) Pleiotropy, natural selection, and the evolution of senescence. Evolution 11:398–411
Wingfield J, Sapolsky R (2003) Reproduction and resistance to stress: when and how. J Neuroendocrinol 15:711–724
Acknowledgments
We thank Bruno Tsiverimana, Léonard Razafimanantsoa and the rest of the Kirindy research station staff, as well as Melanie Dammhahn, Eva Pechouskova, Josue Rakotoniaina and Zo Samuel Ella Fenosoa for their help in collecting data, Andrea Heistermann for conducting the hormone analyses, Peter Kappeler and Rodin Rasoloarison for their administrative and logistic support and Hanta Razafindraibe and the Département de Biologie Animale of the University of Antananarivo for their continued collaboration. Constructive comments by Pawel Koteja and two anonymous reviewers helped improve an earlier version of the manuscript. Ministère de l’Environment et des Eaux et Fôrets, MINEEF Direction des Eaux et Forêts of Madagascar and CNFEREF Morondava permitted research in Kirindy and all research was approved by the appropriate Animal Use and Care committees of Germany (Bundesministerium für Naturschutz, BfN) and complies with the applicable national laws of Madagascar. Funding was provided by the Deutsche Forschungsgemeinschaft (awarded to C.K., KR3834/1-1).
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
All applicable institutional and/or national guidelines for the care and use of animals were followed.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by Pawel Koteja.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Hämäläinen, A., Heistermann, M. & Kraus, C. The stress of growing old: sex- and season-specific effects of age on allostatic load in wild grey mouse lemurs. Oecologia 178, 1063–1075 (2015). https://doi.org/10.1007/s00442-015-3297-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00442-015-3297-3