DNA methylation as a tool to explore ageing in wild roe deer populations

DNA methylation‐based biomarkers of ageing (epigenetic clocks) promise to lead to new insights into evolutionary biology of ageing. Relatively little is known about how the natural environment affects epigenetic ageing effects in wild species. In this study, we took advantage of a unique long‐term (>40 years) longitudinal monitoring of individual roe deer (Capreolus capreolus) living in two wild populations (Chizé and Trois‐Fontaines, France) facing different ecological contexts, to investigate the relationship between chronological age and levels of DNA methylation (DNAm). We generated novel DNA methylation data from n = 94 blood samples, from which we extracted leucocyte DNA, using a custom methylation array (HorvathMammalMethylChip40). We present three DNA methylation‐based estimators of age (DNAm or epigenetic age), which were trained in males, females, and both sexes combined. We investigated how sex differences influenced the relationship between DNAm age and chronological age using sex‐specific epigenetic clocks. Our results highlight that old females may display a lower degree of biological ageing than males. Further, we identify the main sites of epigenetic alteration that have distinct ageing patterns between the two sexes. These findings open the door to promising avenues of research at the crossroads of evolutionary biology and biogerontology.

[1]  S. Alberts,et al.  High social status males experience accelerated epigenetic aging in wild baboons , 2021, eLife.

[2]  Josephine A. Reinhardt,et al.  DNA methylation predicts age and provides insight into exceptional longevity of bats , 2021, Nature Communications.

[3]  Robert W. Williams,et al.  Universal DNA Methylation Age Across Mammalian Tissues , 2021, bioRxiv.

[4]  Soo Bin Kwon,et al.  A mammalian methylation array for profiling methylation levels at conserved sequences , 2021, Nature Communications.

[5]  R. Marioni,et al.  Methylation-Based Age Estimation in a Wild Mouse , 2020, bioRxiv.

[6]  Samson H. Fong,et al.  Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. , 2020, Cell systems.

[7]  D. Belsky,et al.  Social determinants of health and survival in humans and other animals , 2020, Science.

[8]  D. Macdonald,et al.  Reproductive and Somatic Senescence in the European Badger (Meles meles): Evidence from Lifetime Sex-Steroid Profiles. , 2020, Zoology.

[9]  J. Gaillard,et al.  Pathogens Shape Sex Differences in Mammalian Aging , 2020, Trends in Parasitology.

[10]  A. Jasinska Resources for functional genomic studies of health and development in nonhuman primates. , 2020, American journal of physical anthropology.

[11]  Dalia A. Conde,et al.  Sex differences in adult lifespan and aging rates of mortality across wild mammals , 2020, Proceedings of the National Academy of Sciences.

[12]  J. Gaillard,et al.  Going beyond Lifespan in Comparative Biology of Aging , 2020 .

[13]  J. Gaillard,et al.  An integrative view of senescence in nature , 2020, Functional Ecology.

[14]  Benjamin B. Parrott,et al.  Epigenetic Aging Clocks in Ecology and Evolution. , 2019, Trends in ecology & evolution.

[15]  S. Pavard,et al.  Eco‐evolutionary perspectives of the dynamic relationships linking senescence and cancer , 2019, Functional Ecology.

[16]  R. Bonduriansky,et al.  Senescence in wild insects: Key questions and challenges , 2019, Functional Ecology.

[17]  Anne E. Aulsebrook,et al.  Immunosenescence in wild animals: meta-analysis and outlook. , 2019, Ecology letters.

[18]  Lewis G. Spurgin,et al.  Breeders that receive help age more slowly in a cooperatively breeding bird , 2019, Nature Communications.

[19]  J. Gaillard,et al.  Early and Adult Social Environments Shape Sex-Specific Actuarial Senescence Patterns in a Cooperative Breeder , 2018, The American Naturalist.

[20]  P. Laird,et al.  SeSAMe: reducing artifactual detection of DNA methylation by Infinium BeadChips in genomic deletions , 2018, Nucleic acids research.

[21]  E. Dempster,et al.  Application of a novel molecular method to age free‐living wild Bechstein's bats , 2018, Molecular ecology resources.

[22]  Steve Horvath,et al.  DNA methylation-based biomarkers and the epigenetic clock theory of ageing , 2018, Nature Reviews Genetics.

[23]  Shane A. Evans,et al.  Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage-and Histone Methylation-Dependent Pathways , 2018, Cell reports.

[24]  S. Ozanne,et al.  Somatic growth and telomere dynamics in vertebrates: relationships, mechanisms and consequences , 2018, Philosophical Transactions of the Royal Society B: Biological Sciences.

[25]  J. Vaupel,et al.  Women live longer than men even during severe famines and epidemics , 2018, Proceedings of the National Academy of Sciences.

[26]  J. Gaillard,et al.  Reproductive senescence: new perspectives in the wild , 2017, Biological reviews of the Cambridge Philosophical Society.

[27]  J. Tower Sex-Specific Gene Expression and Life Span Regulation , 2017, Trends in Endocrinology & Metabolism.

[28]  J. Gaillard,et al.  The cost of growing large: costs of post‐weaning growth on body mass senescence in a wild mammal , 2017 .

[29]  M. Hindell,et al.  Measuring Animal Age with DNA Methylation: From Humans to Wild Animals , 2017, Front. Genet..

[30]  M. Levine,et al.  DNA methylation-based measures of biological age: meta-analysis predicting time to death , 2016, Aging.

[31]  S. Austad,et al.  Sex Differences in Lifespan. , 2016, Cell metabolism.

[32]  G. Dotto,et al.  Sexual dimorphism in cancer , 2016, Nature Reviews Cancer.

[33]  B. Sæther,et al.  Spatial variation in senescence rates in a bird metapopulation , 2016, Oecologia.

[34]  J. Vaupel,et al.  University of Southern Denmark DNA methylation age is associated with mortality in a longitudinal Danish twin study , 2015 .

[35]  Tom R. Gaunt,et al.  Prenatal and early life influences on epigenetic age in children: a study of mother–offspring pairs from two cohort studies , 2015, Human molecular genetics.

[36]  C. Selman,et al.  Aging in the wild: Insights from free-living and non-model organisms , 2015, Experimental Gerontology.

[37]  M. Briga,et al.  What can long-lived mutants tell us about mechanisms causing aging and lifespan variation in natural environments? , 2015, Experimental Gerontology.

[38]  M. Levine,et al.  DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative , 2015, Aging.

[39]  S. Horvath,et al.  HIV-1 Infection Accelerates Age According to the Epigenetic Clock , 2015, The Journal of infectious diseases.

[40]  G. Pfeifer,et al.  Aging and DNA methylation , 2015, BMC Biology.

[41]  S. Horvath,et al.  DNA methylation age of blood predicts all-cause mortality in later life , 2015, Genome Biology.

[42]  J. Gaillard,et al.  Haematological parameters do senesce in the wild: evidence from different populations of a long‐lived mammal , 2014, Journal of evolutionary biology.

[43]  E. Schadt,et al.  Geroscience: Linking Aging to Chronic Disease , 2014, Cell.

[44]  F. Guinness,et al.  Evaluation of methods to age Scottish red deer: the balance between accuracy and practicality , 2014 .

[45]  Steve Horvath,et al.  Obesity accelerates epigenetic aging of human liver , 2014, Proceedings of the National Academy of Sciences.

[46]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[47]  A. Polanowski,et al.  Epigenetic estimation of age in humpback whales , 2014, Molecular ecology resources.

[48]  S. Horvath DNA methylation age of human tissues and cell types , 2013, Genome Biology.

[49]  Manuel Serrano,et al.  The Hallmarks of Aging , 2013, Cell.

[50]  D. Promislow,et al.  The Size–Life Span Trade-Off Decomposed: Why Large Dogs Die Young , 2013, The American Naturalist.

[51]  N. Metcalfe,et al.  Experimental demonstration of the growth rate–lifespan trade-off , 2013, Proceedings of the Royal Society B: Biological Sciences.

[52]  Jean-Michel Gaillard,et al.  Senescence in natural populations of animals: Widespread evidence and its implications for bio-gerontology , 2013, Ageing Research Reviews.

[53]  Jean-Marie Robine,et al.  Exploring the impact of climate on human longevity , 2012, Experimental Gerontology.

[54]  O. Blin,et al.  The grey mouse lemur: A non-human primate model for ageing studies , 2012, Ageing Research Reviews.

[55]  J. Gaillard,et al.  Patterns of body mass senescence and selective disappearance differ among three species of free-living ungulates. , 2011, Ecology.

[56]  J. Gaillard,et al.  Reproductive constraints, not environmental conditions, shape the ontogeny of sex‐specific mass–size allometry in roe deer , 2011 .

[57]  Cory Y. McLean,et al.  GREAT improves functional interpretation of cis-regulatory regions , 2010, Nature Biotechnology.

[58]  H. Weimerskirch,et al.  Patterns of aging in the long-lived wandering albatross , 2010, Proceedings of the National Academy of Sciences.

[59]  Trevor Hastie,et al.  Regularization Paths for Generalized Linear Models via Coordinate Descent. , 2010, Journal of statistical software.

[60]  L. Partridge The new biology of ageing , 2010, Philosophical Transactions of the Royal Society B: Biological Sciences.

[61]  Craig Packer,et al.  Predatory senescence in ageing wolves. , 2009, Ecology letters.

[62]  Steve Horvath,et al.  WGCNA: an R package for weighted correlation network analysis , 2008, BMC Bioinformatics.

[63]  R. Ricklefs,et al.  The evolutionary ecology of senescence , 2008 .

[64]  L. Kruuk,et al.  Environmental conditions in early life influence ageing rates in a wild population of red deer , 2007, Current Biology.

[65]  A. Mysterud,et al.  Bigger teeth for longer life? Longevity and molar height in two roe deer populations , 2007, Biology Letters.

[66]  N. Pettorelli,et al.  Using a proxy of plant productivity (NDVI) to find key periods for animal performance: the case of roe deer , 2006 .

[67]  J. Gaillard,et al.  Assessing senescence patterns in populations of large mammals , 2004, Animal Biodiversity and Conservation.

[68]  Pat Monaghan,et al.  Growth versus lifespan: perspectives from evolutionary ecology , 2003, Experimental Gerontology.

[69]  J. Gaillard,et al.  Tests of estimation of age from tooth wear on roe deer of known age: variation within and among populations , 1999 .

[70]  Roger Pradel,et al.  Roe deer survival patterns: a comparative analysis of contrasting populations , 1993 .

[71]  John O. Reiss The Meaning of Developmental Time: A Metric for Comparative Embryology , 1989, The American Naturalist.

[72]  S. Hurlbert Pseudoreplication and the Design of Ecological Field Experiments , 1984 .

[73]  J. Gaillard,et al.  Assessing ageing patterns for comparative analyses of mortality curves: Going beyond the use of maximum longevity , 2019, Functional Ecology.

[74]  S. Austad,et al.  Methusaleh's Zoo: how nature provides us with clues for extending human health span. , 2010, Journal of comparative pathology.

[75]  S. Austad,et al.  Senescence in Wild Populations of Mammals and Birds , 2005 .

[76]  J. Jullien,et al.  Intérêt de l'étude de la période juvénile pour le suivi de l'évolution d'une population de chevreuils (Capreolus capreolus) , 1988 .