Skip to main content

Advertisement

SpringerLink
Log in

Access to females and early life castration individually extend maximal but not median lifespan in male mice

  • Original Article
  • Published:
GeroScience Aims and scope Submit manuscript

Abstract

Investment in reproduction is predicted to accelerate ageing, but the link between reproductive investment and lifespan can be sex- and context-specific. In mammals, female reproductive costs are linked to pregnancy and lactation, but in males substantial reproductive allocation is required for a range of pre- and post-copulatory reproductive traits. Such traits include male-specific increased body size, olfactory signalling and territory defence—traits often expressed under androgen-dependent control. In this experimental study, we explored how reproduction influences lifespan in male mice, contrasting this to the established lifespan costs of reproduction in females. In a 2 × 2 factorial design, we gave either castrated or intact males (factor 1) access to a female or a male cage-mate across their entire life (factor 2). Neither castration nor access to females influenced median lifespan in male mice, but maximal lifespan was increased by either castration or reproduction when compared to intact males housed in male groups (standard male housing conditions). In females, mating significantly reduced lifespan, and while both sexes had similar lifespans in non-reproductive environments, males had a much longer lifespan when allowed mating. This data highlights the sex-specific nature of social environments and reproduction on lifespan, and the role of these conditions in promoting sexual dimorphism in ageing.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kirkwood TBL, Austad SN. Why do we age? Nature. 2000;408:233–8.

    Article  CAS  PubMed  Google Scholar 

  2. Kirkwood TBL, Rose MR. Evolution of senescence: late survival sacrificed for reproduction. Philos Trans R Soc Lond Ser B Biol Sci. 1991;332:15–24.

    Article  CAS  Google Scholar 

  3. Promislow DEL, Harvey PH. Living fast and dying young - a comparative-analysis of life-history variation among mammals. J Zool. 1990;220:417–37.

    Article  Google Scholar 

  4. Stearns SC. The evolution of life histories. Oxford: Oxford University Press; 1992.

    Google Scholar 

  5. Barnes AI, Partridge L. Costing reproduction. Anim Behav. 2003;66:199–204.

    Article  Google Scholar 

  6. Speakman JR, Garratt M. Oxidative stress as a cost of reproduction: beyond the simplistic trade-off model. Bioessays. 2014;36:93–106.

    Article  PubMed  Google Scholar 

  7. Braendle C, Heyland A, Flatt T. Integrating mechanistic and evolutionary analysis of life history variation. In: Mechanisms of life history evolution. The genetics and physiology of life history traits and trade-offs; 2011. p. 3–10.

    Chapter  Google Scholar 

  8. Brooks RC, Garratt MG. Life history evolution, reproduction, and the origins of sex-dependent aging and longevity. Ann N Y Acad Sci. 2017;1389:92–107.

    Article  PubMed  Google Scholar 

  9. Lemaître J-F, Berger V, Bonenfant C, Douhard M, Gamelon M, Plard F, et al. Early-late life trade-offs and the evolution of ageing in the wild. Proc R Soc B Biol Sci. 2015;282:20150209.

    Article  Google Scholar 

  10. Green EL. Biology of the laboratory mouse. New York: Dover Publication; 1966.

    Google Scholar 

  11. Flurkey K, Brandvain Y, Klebanov S, Austad SN, Miller RA, Yuan R, et al. PohnB6F1: a cross of wild and domestic mice that is a new model of extended female reproductive life span. J Gerontol Ser A Biol Sci Med Sci. 2007;62:1187–98.

    Article  Google Scholar 

  12. Parker GA. Sperm competition and its evolutionary consequences in insects. Biol Rev Camb Philos Soc. 1970;45:525–67.

    Article  Google Scholar 

  13. Gendron CM, Kuo T-H, Harvanek ZM, Chung BY, Yew JY, Dierick HA, et al. Drosophila life span and physiology are modulated by sexual perception and reward. Science. 2014;343:544–8.

    Article  CAS  PubMed  Google Scholar 

  14. Drori D, Folman Y. Environmental effects on longevity in the male rat: exercise, mating, castration and restricted feeding. Exp Gerontol. 1976;11:25–32.

    Article  CAS  PubMed  Google Scholar 

  15. Jewell PA. Survival and behaviour of castrated Soay sheep (Ovis aries) in a feral island population on Hirta, St. Kilda, Scotland. J Zool. 1997;243:623–36.

    Article  Google Scholar 

  16. Hamilton JB. Relationship of castration, spaying, and sex to survival and duration of life in domestic cats. J Gerontol. 1965;20:96–104.

    Article  CAS  PubMed  Google Scholar 

  17. Hoffman JM, Creevy KE, Promislow DE. Reproductive capability is associated with lifespan and cause of death in companion dogs. PLoS One. 2013;8:e61082.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Min K-J, Lee C-K, Park H-N. The lifespan of Korean eunuchs. Curr Biol. 2012;22:R792–3.

    Article  CAS  PubMed  Google Scholar 

  19. Talbert GB, Hamilton JB. Duration of life in Lewis strain of rats after gonadectomy at birth and at older ages. J Gerontol. 1965;20:489–91.

    CAS  PubMed  Google Scholar 

  20. Nieschlag E, Nieschlag S, Behre HM. Lifespan and testosterone. Nature. 1993;366:215.

    Article  CAS  PubMed  Google Scholar 

  21. Asdell SA, Doornenbal H, Joshi SR, Sperling GA. The effects of sex steroid hormones upon longevity in rats. J Reprod Fertil. 1967;14:113–20.

    Article  CAS  PubMed  Google Scholar 

  22. Clemens LG, Wee BE, Weaver DR, Roy EJ, Goldman BD, Rakerd B. Retention of masculine sexual behavior following castration in male B6D2F1 mice. Physiol Behav. 1988;42:69–76.

    Article  CAS  PubMed  Google Scholar 

  23. McGill TE, Manning A. Genotype and retention of the ejaculatory reflex in castrated male mice. Anim Behav. 1976;24:507–18.

    Article  CAS  PubMed  Google Scholar 

  24. Ladiges W, Van Remmen H, Strong R, Ikeno Y, Treuting P, Rabinovitch P, et al. Lifespan extension in genetically modified mice. Aging Cell. 2009;8:346–52.

    Article  CAS  PubMed  Google Scholar 

  25. Miller RA, Harrison DE, Astle CM, Floyd RA, Flurkey K, Hensley KL, et al. An Aging Interventions Testing Program: study design and interim report. Aging Cell. 2007;6:565–75.

    Article  CAS  PubMed  Google Scholar 

  26. Shoji H, Takao K, Hattori S, Miyakawa T. Age-related changes in behavior in C57BL/6J mice from young adulthood to middle age. Mol Brain. 2016;9:11.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Mangiafico SS. Summary and analysis of extension program evaluation. In: R, version 1.18.1. rcompanionorg/documents/RHandbookProgramEvaluation; 2016.

    Google Scholar 

  28. Yang JS, Nam HJ, Seo M, Han SK, Choi Y, Nam HG, et al. OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS One. 2011;6:e23525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wobbrock JO, Findlater L, Gergle D, Higgins JJ. The aligned rank transform for nonparametric factorial analyses using only anova procedures. In: Proceedings of the SIGCHI conference on human factors in computing systems; 2011. p. 143–6. https://doi.org/10.1145/1978942.1978963.

  30. Davis EJ, Lobach I, Dubal DB. Female XX sex chromosomes increase survival and extend lifespan in aging mice. Aging Cell. 2019;18:e12871.

    Article  PubMed  Google Scholar 

  31. Lemaître J-F, Ronget V, Tidière M, Allainé D, Berger V, Cohas A, et al. Sex differences in adult lifespan and aging rates of mortality across wild mammals. PNAS. 2020;117:8546–53.

    Article  PubMed  Google Scholar 

  32. Perez J, Burunat E, Arevalo R, Rodriguez M. Gonadal influences on behavioral deterioration with aging of male rats. Horm Behav. 1989;23:457–65.

    Article  CAS  PubMed  Google Scholar 

  33. Garratt M, Leander D, Pifer K, Bower B, Herrera JJ, Day SM, et al. 17-alpha estradiol ameliorates age-associated sarcopenia and improves late-life physical function in male mice but not in females or castrated males. Aging Cell. 2019;18:e12920.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Regan JC, Partridge L. Gender and longevity: why do men die earlier than women? Comparative and experimental evidence. Best Pract Res Clin Endocrinol Metab. 2013;27:467–79.

    Article  PubMed  Google Scholar 

  35. Garratt M, Nakagawa S, Simons MJP. Life-span extension with reduced somatotrophic signaling: moderation of aging effect by signal type, sex, and experimental cohort. J Gerontol A Biol Sci Med Sci. 2017;72:1620–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Garratt M, Nakagawa SN, Simons MJ. Comparative idiosyncrasies in life extension by reduced mTOR signalling and its distinctiveness from dietary restriction. Aging Cell. 2016;15:737–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ. 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. 2003;144:3799–810.

    Article  CAS  PubMed  Google Scholar 

  39. Holzenberger M, Dupont J, Ducos B, Leneuve P, Geloen A, Even PC, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003;421:182–7.

    Article  CAS  PubMed  Google Scholar 

  40. Bonduriansky R, Maklakov A, Zajitschek F, Brooks R. Sexual selection, sexual conflict and the evolution of ageing and life span. Funct Ecol. 2008;22:443–53.

    Article  Google Scholar 

  41. Harvanek ZM, Lyu Y, Gendron CM, Johnson JC, Kondo S, Promislow DEL, et al. Perceptive costs of reproduction drive aging and physiology in male Drosophila. Nat Ecol Evol. 2017;1:0152.

    Article  Google Scholar 

  42. Garratt M, Try H, Smiley KO, Grattan DR, Brooks RC. Mating in the absence of fertilization promotes a growth-reproduction versus lifespan trade-off in female mice. PNAS. 2020;117(27):15748–54.

  43. Booth LN, Maures TJ, Yeo RW, Tantilert C, Brunet A. Self-sperm induce resistance to the detrimental effects of sexual encounters with males in hermaphroditic nematodes. eLife. 2019;8:e46418.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Booth LN, Shi C, Tantilert C, Yeo RW, Hebestreit K, Hollenhorst CN, et al. Males deploy multifaceted strategies and hijack longevity pathways to induce premature demise of the opposite sex. bioRxiv. 2020. https://doi.org/10.1101/2020.06.30.181008.

  45. Maures TJ, Booth LN, Benayoun BA, Izrayelit Y, Schroeder FC, Brunet A. Males shorten the life span of C elegans hermaphrodites via secreted compounds. Science. 2014;343:541–4.

    Article  CAS  PubMed  Google Scholar 

  46. Garratt M. Why do sexes differ in lifespan extension? Sex-specific pathways of aging and underlying mechanisms for dimorphic responses. Nutr Health Aging. 2019;5:1–13.

  47. Austad S, Bartke A. Sex differences in longevity and in responses to anti-aging interventions: a mini-review. Gerontology. 2015. https://doi.org/10.1159/000381472.

  48. Stubbins R, Holcomb V, Hong J, Núñez N. Estrogen modulates abdominal adiposity and protects female mice from obesity and impaired glucose tolerance. Eur J Nutr. 2012;51:861–70.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was funded by an Australian Research Council Discovery Grant (DP150100676).

Author information

Authors and Affiliations

  1. Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin, New Zealand

    Michael Garratt

  2. Evolution and Ecology Research Centre, School of Biological, Earth and Environmental Sciences, University of New South Wales, Sydney, New South Wales, 2052, Australia

    Heather Try & Robert C. Brooks

Authors
  1. Michael Garratt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Heather Try
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert C. Brooks
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

This study was designed by Michael Garratt and Robert Brooks, and conducted by Heather Try. Michael Garratt wrote the manuscript with feedback from the other authors.

Corresponding author

Correspondence to Michael Garratt.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

ESM 1

(DOCX 150 kb)

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Garratt, M., Try, H. & Brooks, R.C. Access to females and early life castration individually extend maximal but not median lifespan in male mice. GeroScience 43, 1437–1446 (2021). https://doi.org/10.1007/s11357-020-00308-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11357-020-00308-8

Keywords

Search

Navigation