Why do bats live so long?—Possible molecular mechanisms

Abstract

Contrasting with several theories of ageing, bats are mammals with remarkable longevity despite their high metabolic rate, living on average three times more than other mammals of equal size. The question of how bats live a long time has attracted considerable attention, and they have thus been related to immortal fantasy characters like Dracula in the novel by Bram Stoker. Several ecological and physiological features, such as reduction in mortality risks, delayed sexual maturation and hibernation, have been linked to bats’ long lifespan. However, there is still very little information about the molecular mechanisms associated with the longevity of bats. In this regard, the present work tries to summarize current knowledge about how bats can live for so long, taking into consideration nutritional factors, oxidative metabolism, protein homeostasis, stress resistance, DNA repair, mitochondrial physiology and cancer resistance.

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References

  1. Ahn M, Cui J, Irving AT, Wang L-F (2016) Unique loss of the PYHIN gene family in bats amongst mammals: implications for inflammasome sensing. Sci Rep 6:21722. https://doi.org/10.1038/srep21722

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Austad SN, Fischer KE (1991) Mammalian aging, metabolism, and ecology: evidence from the bats and marsupials. J Gerontol 46:B47–B53. https://doi.org/10.1093/geronj/46.2.B47

    CAS  Article  PubMed  Google Scholar 

  3. Ball HC, Levari-Shariati S, Cooper LN, Aliani M (2018) Comparative metabolomics of aging in a long-lived bat: insights into the physiology of extreme longevity. PLoS ONE 13:e0196154. https://doi.org/10.1371/journal.pone.0196154

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Baudry M, Dubrin R, Beasley L et al (1986) Low levels of calpain activity in Chiroptera brain: implications for mechanisms of aging. Neurobiol Aging 7:255–258. https://doi.org/10.1016/0197-4580(86)90004-7

    CAS  Article  PubMed  Google Scholar 

  5. Bourliere F (1958) The comparative biology of aging. J Gerontol 13:16–24. https://doi.org/10.1093/geronj/13.Suppl_1.16

    Article  Google Scholar 

  6. Brown JCL, McClelland GB, Faure PA et al (2009) Examining the mechanisms responsible for lower ROS release rates in liver mitochondria from the long-lived house sparrow (Passer domesticus) and big brown bat (Eptesicus fuscus) compared to the short-lived mouse (Mus musculus). Mech Ageing Dev 130:467–476. https://doi.org/10.1016/j.mad.2009.05.002

    CAS  Article  PubMed  Google Scholar 

  7. Brunet-Rossinni AK (2004) Reduced free-radical production and extreme longevity in the little brown bat (Myotis lucifugus) versus two non-flying mammals. Mech Ageing Dev 125:11–20. https://doi.org/10.1016/j.mad.2003.09.003

    CAS  Article  PubMed  Google Scholar 

  8. Brunet-Rossinni AK, Austad SN (2004) Ageing studies on bats: a review. Biogerontology 5:211–222. https://doi.org/10.1023/B:BGEN.0000038022.65024.d8

    CAS  Article  PubMed  Google Scholar 

  9. Brunet-Rossinni AK, Wilkinson GS (2010) Methods for age estimation and the study of senescence in bats. In: Kunz TH, Parsons S (eds) Ecological and behavioral methods for the study of bats, 2nd edn. Johns Hopkins University Press, Baltimore, pp 315–326

    Google Scholar 

  10. Buffenstein R, Pinto M (2009) Endocrine function in naturally long-living small mammals. Mol Cell Endocrinol 299:101–111. https://doi.org/10.1016/j.mce.2008.04.021

    CAS  Article  PubMed  Google Scholar 

  11. Caviedes-Vidal E, Karasov WH, Chediack JG et al (2008) Paracellular absorption: a bat breaks the mammal paradigm. PLoS ONE 3:e1425. https://doi.org/10.1371/journal.pone.0001425

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Cesare AJ, Reddel RR (2010) Alternative lengthening of telomeres: models, mechanisms and implications. Nat Rev Genet 11:319–330. https://doi.org/10.1038/nrg2763

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Claesson MJ, Cusack S, O’Sullivan O et al (2011) Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci USA 108:4586–4591. https://doi.org/10.1073/pnas.1000097107

    Article  PubMed  Google Scholar 

  14. Costantini D, Lindecke O, Pētersons G, Voigt CC (2019) Migratory flight imposes oxidative stress in bats. Curr Zool 65:147–153. https://doi.org/10.1093/cz/zoy039

    Article  PubMed  Google Scholar 

  15. Craik JD, Markovich D (2000) Rapid GLUT-1 mediated glucose transport in erythrocytes from the grey-headed fruit bat (Pteropus poliocephalus). Comp Biochem Physiol A 126:45–55. https://doi.org/10.1016/S1095-6433(00)00177-X

    CAS  Article  Google Scholar 

  16. Croco E, Marchionni S, Bocchini M et al (2016) DNA damage detection by 53BP1: relationship to species longevity. J Gerontol A. https://doi.org/10.1093/gerona/glw170

    Article  Google Scholar 

  17. Currie SE, Noy K, Geiser F (2015) Passive rewarming from torpor in hibernating bats: minimizing metabolic costs and cardiac demands. Am J Physiol Integr Comp Physiol 308:R34–R41. https://doi.org/10.1152/ajpregu.00341.2014

    CAS  Article  Google Scholar 

  18. Eddy SF, McNally JD, Storey KB (2005) Up-regulation of a thioredoxin peroxidase-like protein, proliferation-associated gene, in hibernating bats. Arch Biochem Biophys 435:103–111. https://doi.org/10.1016/j.abb.2004.11.020

    CAS  Article  PubMed  Google Scholar 

  19. Fleischer T, Gampe J, Scheuerlein A, Kerth G (2017) Rare catastrophic events drive population dynamics in a bat species with negligible senescence. Sci Rep 7:7370. https://doi.org/10.1038/s41598-017-06392-9

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Foley NM, Hughes GM, Huang Z et al (2018) Growing old, yet staying young: the role of telomeres in bats’ exceptional longevity. Sci Adv. https://doi.org/10.1126/sciadv.aao0926

    Article  PubMed  PubMed Central  Google Scholar 

  21. Harper JM, Salmon AB, Leiser SF et al (2007) Skin-derived fibroblasts from long-lived species are resistant to some, but not all, lethal stresses and to the mitochondrial inhibitor rotenone. Aging Cell 6:1–13. https://doi.org/10.1111/j.1474-9726.2006.00255.x

    CAS  Article  PubMed  Google Scholar 

  22. Hernández-Arciga U, Herrera MLG, Ibáñez-Contreras A et al (2018) Baseline and post-stress seasonal changes in immunocompetence and redox state maintenance in the fishing bat Myotis vivesi. PLoS ONE 13:e0190047. https://doi.org/10.1371/journal.pone.0190047

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Herreid CF (1964) Bat longevity and metabolic rate. Exp Gerontol 1:1–9. https://doi.org/10.1016/0531-5565(64)90002-6

    Article  Google Scholar 

  24. Holmes DJ, Austad SN (1994) Fly now, die later: life-history correlates of gliding and flying in mammals. J Mammal 75:224–226. https://doi.org/10.2307/1382255

    Article  Google Scholar 

  25. Huang Z, Jebb D, Teeling EC (2016) Blood miRNomes and transcriptomes reveal novel longevity mechanisms in the long-lived bat, Myotis myotis. BMC Genom 17:906. https://doi.org/10.1186/s12864-016-3227-8

    CAS  Article  Google Scholar 

  26. Hughes GM, Leech J, Puechmaille SJ et al (2018) Is there a link between aging and microbiome diversity in exceptional mammalian longevity? PeerJ 6:e4174. https://doi.org/10.7717/peerj.4174

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Jebb D, Foley NM, Whelan CV et al (2018) Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the free radical theory of ageing. Sci Rep 8:13634. https://doi.org/10.1038/s41598-018-31093-2

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  28. Kelm DH, Simon R, Kuhlow D et al (2011) High activity enables life on a high-sugar diet: blood glucose regulation in nectar-feeding bats. Proc R Soc B 278:3490–3496. https://doi.org/10.1098/rspb.2011.0465

    CAS  Article  PubMed  Google Scholar 

  29. Khaidakov M, Siegel ER, Shmookler Reis RJ (2006) Direct repeats in mitochondrial DNA and mammalian lifespan. Mech Ageing Dev 127:808–812. https://doi.org/10.1016/j.mad.2006.07.008

    CAS  Article  PubMed  Google Scholar 

  30. Kirkwood TBL (1977) Evolution of ageing. Nature 270:301–304. https://doi.org/10.1038/270301a0

    CAS  Article  PubMed  Google Scholar 

  31. Koga H, Kaushik S, Cuervo AM (2011) Protein homeostasis and aging: the importance of exquisite quality control. Ageing Res Rev 10:205–215. https://doi.org/10.1016/j.arr.2010.02.001

    CAS  Article  PubMed  Google Scholar 

  32. Lambert MJ, Portfors CV (2017) Adaptive sequence convergence of the tumor suppressor ADAMTS9 between small-bodied mammals displaying exceptional longevity. Aging (Albany NY) 9:573–582. https://doi.org/10.18632/aging.101180

    CAS  Article  Google Scholar 

  33. Lei M, Dong D, Mu S et al (2014) Comparison of brain transcriptome of the Greater horseshoe bats (Rhinolophus ferrumequinum) in active and torpid episodes. PLoS ONE 9:e107746. https://doi.org/10.1371/journal.pone.0107746

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Lilley TM, Stauffer J, Kanerva M, Eeva T (2014) Interspecific variation in redox status regulation and immune defence in five bat species: the role of ectoparasites. Oecologia 175:811–823. https://doi.org/10.1007/s00442-014-2959-x

    CAS  Article  PubMed  Google Scholar 

  35. Liu S, Sun K, Jiang T et al (2012) Natural epigenetic variation in the female great roundleaf bat (Hipposideros armiger) populations. Mol Genet Genom 287:643–650. https://doi.org/10.1007/s00438-012-0704-x

    CAS  Article  Google Scholar 

  36. Liu S, Sun K, Jiang T, Feng J (2015) Natural epigenetic variation in bats and its role in evolution. J Exp Biol 218:100–106. https://doi.org/10.1242/jeb.107243

    Article  PubMed  Google Scholar 

  37. Moosmann B, Behl C (2008) Mitochondrially encoded cysteine predicts animal lifespan. Aging Cell 7:32–46. https://doi.org/10.1111/j.1474-9726.2007.00349.x

    CAS  Article  PubMed  Google Scholar 

  38. Munshi-South J, Wilkinson GS (2010) Bats and birds: exceptional longevity despite high metabolic rates. Ageing Res Rev 9:12–19. https://doi.org/10.1016/j.arr.2009.07.006

    CAS  Article  PubMed  Google Scholar 

  39. Petri B, von Haeseler A, Pääbo S (1996) Extreme sequence heteroplasmy in bat mitochondrial DNA. Biol Chem 377:661–667

    CAS  PubMed  Google Scholar 

  40. Podlutsky AJ, Khritankov AM, Ovodov ND, Austad SN (2005) A new field record for bat longevity. J Gerontol A 60:1366–1368. https://doi.org/10.1093/gerona/60.11.1366

    Article  Google Scholar 

  41. Pollard AK, Ingram TL, Ortori CA et al (2019) A comparison of the mitochondrial proteome and lipidome in the mouse and long-lived Pipistrelle bats. Aging (Albany NY) 11:1664–1685. https://doi.org/10.18632/aging.101861

    CAS  Article  Google Scholar 

  42. Pride H, Yu Z, Sunchu B et al (2015) Long-lived species have improved proteostasis compared to phylogenetically-related shorter-lived species. Biochem Biophys Res Commun 457:669–675. https://doi.org/10.1016/j.bbrc.2015.01.046

    CAS  Article  PubMed  Google Scholar 

  43. Ransome RD (1995) Earlier breeding shortens life in female greater horseshoe bats. Philos Trans R Soc London B 350:153–161. https://doi.org/10.1098/rstb.1995.0149

    Article  Google Scholar 

  44. Salmon AB, Leonard S, Masamsetti V et al (2009) The long lifespan of two bat species is correlated with resistance to protein oxidation and enhanced protein homeostasis. FASEB J 23:2317–2326. https://doi.org/10.1096/fj.08-122523

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  45. Schneeberger K, Czirják GÁ, Voigt CC (2014) Frugivory is associated with low measures of plasma oxidative stress and high antioxidant concentration in free-ranging bats. Naturwissenschaften 101:285–290. https://doi.org/10.1007/s00114-014-1155-5

    CAS  Article  PubMed  Google Scholar 

  46. Seim I, Fang X, Xiong Z et al (2013) Genome analysis reveals insights into physiology and longevity of the Brandt’s bat Myotis brandtii. Nat Commun 4:2212. https://doi.org/10.1038/ncomms3212

    Article  PubMed  PubMed Central  Google Scholar 

  47. Shen Y-Y, Liang L, Zhu Z-H et al (2010) Adaptive evolution of energy metabolism genes and the origin of flight in bats. Proc Natl Acad Sci USA 107:8666–8671. https://doi.org/10.1073/pnas.0912613107

    Article  PubMed  Google Scholar 

  48. Suarez R, Welch K (2017) Sugar metabolism in hummingbirds and nectar bats. Nutrients 9:743. https://doi.org/10.3390/nu9070743

    CAS  Article  PubMed Central  Google Scholar 

  49. Tacutu R, Thornton D, Johnson E et al (2018) Human ageing genomic resources: new and updated databases. Nucleic Acids Res 46:D1083–D1090. https://doi.org/10.1093/nar/gkx1042

    CAS  Article  PubMed  Google Scholar 

  50. Teeling EC (2009) Bats (Chiroptera). In: Blair-Hedges S, Kumar S (eds) The timetree of life. Oxford University Press, New York, pp 499–503

    Google Scholar 

  51. Tracy CR, McWhorter TJ, Korine C et al (2007) Absorption of sugars in the Egyptian fruit bat (Rousettus aegyptiacus): a paradox explained. J Exp Biol 210:1726–1734. https://doi.org/10.1242/jeb.02766

    CAS  Article  PubMed  Google Scholar 

  52. Turbill C, Bieber C, Ruf T (2011) Hibernation is associated with increased survival and the evolution of slow life histories among mammals. Proc R Soc B 278:3355–3363. https://doi.org/10.1098/rspb.2011.0190

    Article  PubMed  Google Scholar 

  53. van der Goot AT, Nollen EAA (2013) Tryptophan metabolism: entering the field of aging and age-related pathologies. Trends Mol Med 19:336–344. https://doi.org/10.1016/j.molmed.2013.02.007

    CAS  Article  PubMed  Google Scholar 

  54. Vengust M, Knapic T, Weese JS (2018) The fecal bacterial microbiota of bats, Slovenia. PLoS ONE 13:e0196728. https://doi.org/10.1371/journal.pone.0196728

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  55. West J, Widschwendter M, Teschendorff AE (2013) Distinctive topology of age-associated epigenetic drift in the human interactome. Proc Natl Acad Sci USA 110:14138–14143. https://doi.org/10.1073/pnas.1307242110

    Article  PubMed  Google Scholar 

  56. Widmaier EP, Gornstein ER, Hennessey JL et al (1996) High plasma cholesterol, but low triglycerides and plaque-free arteries, in Mexican free-tailed bats. Am J Physiol Integr Comp Physiol 271:R1101–R1106. https://doi.org/10.1152/ajpregu.1996.271.5.R1101

    CAS  Article  Google Scholar 

  57. Wilhelm Filho D, Althoff SL, Dafré AL, Boveris A (2007) Antioxidant defenses, longevity and ecophysiology of South American bats. Comp Biochem Physiol C 146:214–220. https://doi.org/10.1016/j.cbpc.2006.11.015

    CAS  Article  Google Scholar 

  58. Wilkinson GS, Adams DM (2019) Recurrent evolution of extreme longevity in bats. Biol Lett 15:20180860. https://doi.org/10.1098/rsbl.2018.0860

    Article  PubMed  PubMed Central  Google Scholar 

  59. Wilkinson GS, South JM (2002) Life history, ecology and longevity in bats. Aging Cell 1:124–131. https://doi.org/10.1046/j.1474-9728.2002.00020.x

    CAS  Article  PubMed  Google Scholar 

  60. Wright PGR, Mathews F, Schofield H et al (2018) Application of a novel molecular method to age free-living wild Bechstein’s bats. Mol Ecol Resour 18:1374–1380. https://doi.org/10.1111/1755-0998.12925

    CAS  Article  PubMed  Google Scholar 

  61. Yin Q, Ge H, Liao C-C et al (2016a) Antioxidant defenses in the brains of bats during hibernation. PLoS ONE 11:e0152135. https://doi.org/10.1371/journal.pone.0152135

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  62. Yin Q, Zhu L, Liu D et al (2016b) Molecular evolution of the nuclear factor (erythroid-derived 2)-like 2 gene Nrf2 in old world fruit bats (Chiroptera: Pteropodidae). PLoS ONE 11:e0146274. https://doi.org/10.1371/journal.pone.0146274

    Article  PubMed  PubMed Central  Google Scholar 

  63. Zhang G, Cowled C, Shi Z et al (2013a) Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science. https://doi.org/10.1126/science.1230835

    Article  PubMed  PubMed Central  Google Scholar 

  64. Zhang Y, Zhu T, Wang L et al (2013b) Homocysteine homeostasis and betaine-homocysteine S-methyltransferase expression in the brain of hibernating bats. PLoS ONE 8:e85632. https://doi.org/10.1371/journal.pone.0085632

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  65. Zhang Y, Pan Y-H, Yin Q et al (2014) Critical roles of mitochondria in brain activities of torpid Myotis ricketti bats revealed by a proteomic approach. J Proteom 105:266–284. https://doi.org/10.1016/j.jprot.2014.01.006

    CAS  Article  Google Scholar 

  66. Zhang Q, Zeng L-P, Zhou P et al (2017) IFNAR2-dependent gene expression profile induced by IFN-α in Pteropus alecto bat cells and impact of IFNAR2 knockout on virus infection. PLoS ONE 12:e0182866. https://doi.org/10.1371/journal.pone.0182866

    CAS  Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

FALR is recipient of a doctoral scholarship (Application Number 2018-000012-01NACF-07226) from the National Council of Science and Technology, CONACyT.

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Correspondence to Francisco Alejandro Lagunas-Rangel.

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Lagunas-Rangel, F.A. Why do bats live so long?—Possible molecular mechanisms. Biogerontology 21, 1–11 (2020). https://doi.org/10.1007/s10522-019-09840-3

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Keywords

  • Chiroptera
  • Ageing
  • Oxidative metabolism
  • DNA repair