1932

Abstract

Naked mole-rats (NMRs, ) are the longest-lived rodents with a maximum life span exceeding 37 years. They exhibit a delayed aging phenotype and resistance to age-related functional decline/diseases. Specifically, they do not display increased mortality with age, maintain several physiological functions until nearly the end of their lifetime, and rarely develop cancer and Alzheimer's disease. NMRs live in a hypoxic environment in underground colonies in East Africa and are highly tolerant of hypoxia. These unique characteristics of NMRs have attracted considerable interest from zoological and biomedical researchers. This review summarizes previous studies of the ecology, hypoxia tolerance, longevity/delayed aging, and cancer resistance of NMRs and discusses possible mechanisms contributing to their healthy aging. In addition, we discuss current issues and future perspectives to fully elucidate the mechanisms underlying delayed aging and resistance to age-related diseases in NMRs.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-animal-050322-074744
2023-02-15
2024-10-14
Loading full text...

Full text loading...

/deliver/fulltext/animal/11/1/annurev-animal-050322-074744.html?itemId=/content/journals/10.1146/annurev-animal-050322-074744&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Johnson SC, Rabinovitch PS, Kaeberlein M. 2013. mTOR is a key modulator of ageing and age-related disease. Nature 493:7432338–45
    [Google Scholar]
  2. 2.
    Fontana L, Partridge L, Longo VD. 2010. Extending healthy life span—from yeast to humans. Science 328:5976321–26
    [Google Scholar]
  3. 3.
    Speakman JR. 2005. Body size, energy metabolism and lifespan. J. Exp. Biol. 208:91717–30
    [Google Scholar]
  4. 4.
    Vincze O, Colchero F, Lemaître J-F, Conde DA, Pavard S et al. 2022. Cancer risk across mammals. Nature 601:7892263–67
    [Google Scholar]
  5. 5.
    Keane M, Semeiks J, Webb AE, Li YI, Quesada V et al. 2015. Insights into the evolution of longevity from the bowhead whale genome. Cell Rep 10:1112–22
    [Google Scholar]
  6. 6.
    Zhao Y, Oreskovic E, Zhang Q, Lu Q, Gilman A et al. 2021. Transposon-triggered innate immune response confers cancer resistance to the blind mole rat. Nat. Immunol. 22:101219–30
    [Google Scholar]
  7. 7.
    Abegglen LM, Caulin AF, Chan A, Lee K, Robinson R et al. 2015. Potential mechanisms for cancer resistance in elephants and comparative cellular response to DNA damage in humans. JAMA 314:171850–60
    [Google Scholar]
  8. 8.
    Jarvis JUM. 1981. Eusociality in a mammal: cooperative breeding in naked mole-rat colonies. Science 212:4494571–73
    [Google Scholar]
  9. 9.
    Buffenstein R, Amoroso V, Andziak B, Avdieiev S, Azpurua J et al. 2022. The naked truth: a comprehensive clarification and classification of current ‘myths’ in naked mole-rat biology. Biol. Rev. 97:1115–40
    [Google Scholar]
  10. 10.
    Crespi BJ, Yanega D. 1995. The definition of eusociality. Behav. Ecol. 6:1109–15
    [Google Scholar]
  11. 11.
    Lee BP, Smith M, Buffenstein R, Harries LW. 2020. Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation. GeroScience 42:2633–51
    [Google Scholar]
  12. 12.
    Ruby JG, Smith M, Buffenstein R 2018. Naked mole-rat mortality rates defy Gompertzian laws by not increasing with age. eLife 7:e31157
    [Google Scholar]
  13. 13.
    Buffenstein R. 2008. Negligible senescence in the longest living rodent, the naked mole-rat: insights from a successfully aging species. J. Comp. Physiol. B. 178:4439–45
    [Google Scholar]
  14. 14.
    Can E, Smith M, Boukens BJ, Coronel R, Buffenstein R, Riegler J. 2022. Naked mole-rats maintain cardiac function and body composition well into their fourth decade of life. GeroScience 44:731–46
    [Google Scholar]
  15. 15.
    Oka K, Fujioka S, Kawamura Y, Komohara Y, Chujo T et al. 2022. Resistance to chemical carcinogenesis induction via a dampened inflammatory response in naked mole-rats. Commun. Biol. 5:287
    [Google Scholar]
  16. 16.
    Edrey YH, Medina DX, Gaczynska M, Osmulski PA, Oddo S et al. 2013. Amyloid beta and the longest-lived rodent: the naked mole-rat as a model for natural protection from Alzheimer's disease. Neurobiol. Aging 34:102352–60
    [Google Scholar]
  17. 17.
    Munro D, Baldy C, Pamenter ME, Treberg JR. 2019. The exceptional longevity of the naked mole-rat may be explained by mitochondrial antioxidant defenses. Aging Cell 18:3e12916
    [Google Scholar]
  18. 18.
    MacRae SL, Croken MM, Calder RB, Aliper A, Milholland B et al. 2015. DNA repair in species with extreme lifespan differences. Aging 7:121171–82
    [Google Scholar]
  19. 19.
    Azpurua J, Ke Z, Chen IX, Zhang Q, Ermolenko DN et al. 2013. Naked mole-rat has increased translational fidelity compared with the mouse, as well as a unique 28S ribosomal RNA cleavage. PNAS 110:4317350–55
    [Google Scholar]
  20. 20.
    Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV et al. 2011. Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479:7372223–27
    [Google Scholar]
  21. 21.
    Tian X, Azpurua J, Hine C, Vaidya A, Myakishev-Rempel M et al. 2013. High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499:7458346–49
    [Google Scholar]
  22. 22.
    Miyawaki S, Kawamura Y, Oiwa Y, Shimizu A, Hachiya T et al. 2016. Tumour resistance in induced pluripotent stem cells derived from naked mole-rats. Nat. Commun. 7:111471
    [Google Scholar]
  23. 23.
    Kawamura Y, Oka K, Takamori M, Sugiura Y, Oiwa Y et al. 2020. Senescent cell death as an aging resistance mechanism in naked mole-rat. bioRxiv. 155903. https://doi.org/10.1101/2020.07.02.155903
    [Crossref]
  24. 24.
    Faulkes CG, Bennett NC 2021. Social evolution in African mole-rats—a comparative overview. The Extraordinary Biology of the Naked Mole-Rat R Buffenstein, TJ Park, MM Holmes 1–33 Cham, Switz.: Springer Nat.
    [Google Scholar]
  25. 25.
    O'Riain MJ, Jarvis JUM. 1997. Colony member recognition and xenophobia in the naked mole-rat. Anim. Behav. 53:3487–98
    [Google Scholar]
  26. 26.
    Barker AJ, Veviurko G, Bennett NC, Hart DW, Mograby L, Lewin GR. 2021. Cultural transmission of vocal dialect in the naked mole-rat. Science 371:6528503–7
    [Google Scholar]
  27. 27.
    Faulkes CG, Abbott DH, Jarvis JUM. 1990. Social suppression of ovarian cyclicity in captive and wild colonies of naked mole-rats, Heterocephalus glaber. Reproduction 88:2559–68
    [Google Scholar]
  28. 28.
    Faulkes CG, Abbott DH, Jarvis JUM. 1991. Social suppression of reproduction in male naked mole-rats, Heterocephalus glaber. Reproduction 91:2593–604
    [Google Scholar]
  29. 29.
    Gilbert JD, Rossiter SJ, Faulkes CG. 2020. The relationship between individual phenotype and the division of labour in naked mole-rats: It's complicated. PeerJ 8:e9891
    [Google Scholar]
  30. 30.
    Siegmann S, Feitsch R, Hart DW, Bennett NC, Penn DJ, Zöttl M. 2021. Naked mole-rats (Heterocephalus glaber) do not specialise in cooperative tasks. Ethology 127:10850–64
    [Google Scholar]
  31. 31.
    Watarai A, Arai N, Miyawaki S, Okano H, Miura K et al. 2018. Responses to pup vocalizations in subordinate naked mole-rats are induced by estradiol ingested through coprophagy of queen's feces. PNAS 115:379264–69
    [Google Scholar]
  32. 32.
    Edwards PD, Arguelles DA, Mastromonaco GF, Holmes MM. 2021. Queen pregnancy increases group estradiol levels in cooperatively breeding naked mole-rats. Integr. Comp. Biol. 61:51841–51
    [Google Scholar]
  33. 33.
    Faulkes CG, Abbott DH. 1993. Evidence that primer pheromones do not cause social suppression of reproduction in male and female naked mole-rats (Heterocephalus glaber). Reproduction 99:1225–30
    [Google Scholar]
  34. 34.
    Peragine DE, Pokarowski M, Mendoza-Viveros L, Swift-Gallant A, Cheng H-YM et al. 2017. RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal. PNAS 114:51207–12
    [Google Scholar]
  35. 35.
    Faykoo-Martinez M, Kalinowski LM, Holmes MM. 2021. Neuroendocrine regulation of pubertal suppression in the naked mole-rat: what we know and what comes next. Mol. Cell. Endocrinol. 534:111360
    [Google Scholar]
  36. 36.
    Dammann P, Burda H. 2006. Sexual activity and reproduction delay ageing in a mammal. Curr. Biol. 16:4R117–18
    [Google Scholar]
  37. 37.
    Sahm A, Bens M, Henning Y, Vole C, Groth M et al. 2018. Higher gene expression stability during aging in long-lived giant mole-rats than in short-lived rats. Aging 10:123938–56
    [Google Scholar]
  38. 38.
    Fang X, Seim I, Huang Z, Gerashchenko M, Xiong Z et al. 2014. Adaptations to a subterranean environment and longevity revealed by the analysis of mole rat genomes. Cell Rep 8:51354–64
    [Google Scholar]
  39. 39.
    Metcalfe NB, Monaghan P. 2003. Growth versus lifespan: perspectives from evolutionary ecology. Exp. Gerontol. 38:9935–40
    [Google Scholar]
  40. 40.
    Lemaître J-F, Berger V, Bonenfant C, Douhard M, Gamelon M et al. 2015. Early-late life trade-offs and the evolution of ageing in the wild. Proc. R. Soc. B 282:180620150209
    [Google Scholar]
  41. 41.
    Gaillard J-M, Lemaître J-F. 2017. The Williams’ legacy: a critical reappraisal of his nine predictions about the evolution of senescence. Evolution 71:122768–85
    [Google Scholar]
  42. 42.
    Novikov EA, Burda G. 2013. Ecological and evolutionary preconditions of extended longevity in subterranean rodents. Biol. Bull. Rev. 3:4325–33
    [Google Scholar]
  43. 43.
    Kulikov VP, Tregub PP, Osipov IS, Trukhanov AI. 2019. Hypercapnic hypoxia as a potential means to extend life expectancy and improve physiological activity in mice. Biogerontology 20:5677–86
    [Google Scholar]
  44. 44.
    Jarvis JU, O'Riain MJ, Bennett NC, Sherman PW. 1994. Mammalian eusociality: a family affair. Trends Ecol. Evol. 9:247–51
    [Google Scholar]
  45. 45.
    Healy K, Guillerme T, Finlay S, Kane A, Kelly SBA et al. 2014. Ecology and mode-of-life explain lifespan variation in birds and mammals. Proc. R. Soc. B 281:178420140298
    [Google Scholar]
  46. 46.
    Healy K. 2015. Eusociality but not fossoriality drives longevity in small mammals. Proc. R. Soc. B 282:180620142917
    [Google Scholar]
  47. 47.
    Thorley J. 2020. The case for extended lifespan in cooperatively breeding mammals: a re-appraisal. PeerJ 8:e9214
    [Google Scholar]
  48. 48.
    Lucas ER, Keller L. 2020. The co-evolution of longevity and social life. Funct. Ecol. 34:176–87
    [Google Scholar]
  49. 49.
    Downing PA, Cornwallis CK, Griffin AS. 2015. Sex, long life and the evolutionary transition to cooperative breeding in birds. Proc. Biol. Sci. 282:181620151663
    [Google Scholar]
  50. 50.
    Beauchamp G. 2014. Do avian cooperative breeders live longer?. Proc. R. Soc. B 281:178720140844
    [Google Scholar]
  51. 51.
    Bordone L, Guarente L. 2005. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat. Rev. Mol. Cell Biol. 6:4298–305
    [Google Scholar]
  52. 52.
    Yahav S, Buffenstein R. 1991. Huddling behavior facilitates homeothermy in the naked mole rat Heterocephalus glaber. Physiol. Zool. 64:3871–84
    [Google Scholar]
  53. 53.
    Buffenstein R, Yahav S. 1991. Is the naked mole-rat Hererocephalus glaber an endothermic yet poikilothermic mammal?. J. Therm. Biol. 16:4227–32
    [Google Scholar]
  54. 54.
    Bennett N, Jarvis J, Cotterill F 2009. Poikilothermic traits and thermoregulation in the Afrotropical social subterranean Mashona mole-rat (Cryptomys hottentotus darlingi) (Rodentia: Bathyergidae). J. Zool. 231:2179–86
    [Google Scholar]
  55. 55.
    Sahm A, Bens M, Szafranski K, Holtze S, Groth M et al. 2018. Long-lived rodents reveal signatures of positive selection in genes associated with lifespan. PLOS Genet 14:3e1007272
    [Google Scholar]
  56. 56.
    Šumbera R. 2019. Thermal biology of a strictly subterranean mammalian family, the African mole-rats (Bathyergidae, Rodentia)—a review. J. Therm. Biol. 79:166–89
    [Google Scholar]
  57. 57.
    Kirby AM, Fairman GD, Pamenter ME. 2018. Atypical behavioural, metabolic and thermoregulatory responses to hypoxia in the naked mole rat (Heterocephalus glaber). J. Zool. 305:2106–15
    [Google Scholar]
  58. 58.
    Park TJ, Reznick J, Peterson BL, Blass G, Omerbašić D et al. 2017. Fructose-driven glycolysis supports anoxia resistance in the naked mole-rat. Science 356:6335307–11
    [Google Scholar]
  59. 59.
    Holtze S, Braude S, Lemma A, Koch R, Morhart M et al. 2018. The microenvironment of naked mole-rat burrows in East Africa. Afr. J. Ecol. 56:2279–89
    [Google Scholar]
  60. 60.
    Pamenter ME, Dzal YA, Milsom WK. 2015. Adenosine receptors mediate the hypoxic ventilatory response but not the hypoxic metabolic response in the naked mole rat during acute hypoxia. Proc. R. Soc. B 282:180020141722
    [Google Scholar]
  61. 61.
    Pamenter ME, Lau GY, Richards JG, Milsom WK. 2018. Naked mole rat brain mitochondria electron transport system flux and H+ leak are reduced during acute hypoxia. J. Exp. Biol. 221:4jeb171397
    [Google Scholar]
  62. 62.
    Vandewint AL, Zhu-Pawlowsky AJ, Kirby A, Tattersall GJ, Pamenter ME. 2019. Evaporative cooling and vasodilation mediate thermoregulation in naked mole-rats during normoxia but not hypoxia. J. Therm. Biol. 84:228–35
    [Google Scholar]
  63. 63.
    Houlahan CR, Kirby AM, Dzal YA, Fairman GD, Pamenter ME. 2018. Divergent behavioural responses to acute hypoxia between individuals and groups of naked mole rats. Comp. Biochem. Physiol. B 224:38–44
    [Google Scholar]
  64. 64.
    Cheng H, Sebaa R, Malholtra N, Lacoste B, El Hankouri Z et al. 2021. Naked mole-rat brown fat thermogenesis is diminished during hypoxia through a rapid decrease in UCP1. Nat. Commun. 12:6801
    [Google Scholar]
  65. 65.
    Farhat E, Devereaux ME, Pamenter ME, Weber J-M. 2020. Naked mole-rats suppress energy metabolism and modulate membrane cholesterol in chronic hypoxia. Am. J. Physiol. Regul. Integr. Comp. Physiol. 319:2R148–55
    [Google Scholar]
  66. 66.
    Ma YL, Zhu X, Rivera PM, Tøien Ø, Barnes BM et al. 2005. Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289:5R1297–306
    [Google Scholar]
  67. 67.
    Blackstone E, Roth MB. 2007. Suspended animation-like state protects mice from lethal hypoxia. Shock 27:4370–72
    [Google Scholar]
  68. 68.
    Drew KL, Harris MB, LaManna JC, Smith MA, Zhu XW, Ma YL. 2004. Hypoxia tolerance in mammalian heterotherms. J. Exp. Biol. 207:183155–62
    [Google Scholar]
  69. 69.
    Oiwa Y, Oka K, Yasui H, Higashikawa K, Bono H et al. 2020. Characterization of brown adipose tissue thermogenesis in the naked mole-rat (Heterocephalus glaber), a heterothermic mammal. Sci. Rep. 10:19488
    [Google Scholar]
  70. 70.
    McNab BK. 1966. The metabolism of fossorial rodents: a study of convergence. Ecology 47:5712–33
    [Google Scholar]
  71. 71.
    Longo VD, Finch CE. 2003. Evolutionary medicine: From dwarf model systems to healthy centenarians?. Science 299:56111342–46
    [Google Scholar]
  72. 72.
    Zhao Z, Cao J, Niu C, Bao M, Xu J et al. 2022. Body temperature is a more important modulator of lifespan than metabolic rate in two small mammals. Nat. Metab. 4:3320–26
    [Google Scholar]
  73. 73.
    Buffenstein R, Pinto M. 2009. Endocrine function in naturally long-living small mammals. Mol. Cell. Endocrinol. 299:1101–11
    [Google Scholar]
  74. 74.
    Buffenstein R. 2005. The naked mole-rat: a new long-living model for human aging research. J. Gerontol. A 60:111369–77
    [Google Scholar]
  75. 75.
    Lau GY, Milsom WK, Richards JG, Pamenter ME. 2020. Heart mitochondria from naked mole-rats (Heterocephalus glaber) are more coupled, but similarly susceptible to anoxia-reoxygenation stress than in laboratory mice (Mus musculus). Comp. Biochem. Physiol. B 240:110375
    [Google Scholar]
  76. 76.
    Zions M, Meehan EF, Kress ME, Thevalingam D, Jenkins EC et al. 2020. Nest carbon dioxide masks GABA-dependent seizure susceptibility in the naked mole-rat. Curr. Biol. 30:112068–77
    [Google Scholar]
  77. 77.
    Shoubridge EA, Hochachka PW. 1980. Ethanol: novel end product of vertebrate anaerobic metabolism. Science 209:4453308–9
    [Google Scholar]
  78. 78.
    Jackson DC. 2002. Hibernating without oxygen: physiological adaptations of the painted turtle. J. Physiol. 543:3731–37
    [Google Scholar]
  79. 79.
    Pamenter ME, Dzal YA, Thompson WA, Milsom WK. 2019. Do naked mole rats accumulate a metabolic acidosis or an oxygen debt in severe hypoxia?. J. Exp. Biol. 222:3jeb191197
    [Google Scholar]
  80. 80.
    Smith ESJ, Omerbašić D, Lechner SG, Anirudhan G, Lapatsina L, Lewin GR. 2011. The molecular basis of acid insensitivity in the African naked mole-rat. Science 334:60621557–60
    [Google Scholar]
  81. 81.
    Husson Z, Smith ESJ. 2018. Naked mole-rat cortical neurons are resistant to acid-induced cell death. Mol. Brain 11:26
    [Google Scholar]
  82. 82.
    Johansen K, Lykkeboe G, Weber RE, Maloiy GMO. 1976. Blood respiratory properties in the naked mole rat Heterocephalus glaber, a mammal of low body temperature. Respir. Physiol. 28:3303–14
    [Google Scholar]
  83. 83.
    Browe BM, Vice EN, Park TJ. 2020. Naked mole-rats: blind, naked, and feeling no pain. Anat. Rec. 303:177–88
    [Google Scholar]
  84. 84.
    Lenzen S. 2014. A fresh view of glycolysis and glucokinase regulation: history and current status. J. Biol. Chem. 289:1812189–94
    [Google Scholar]
  85. 85.
    Augereau A, Mariotti M, Pousse M, Filipponi D, Libert F et al. 2021. Naked mole rat TRF1 safeguards glycolytic capacity and telomere replication under low oxygen. Sci. Adv. 7:8eabe0174
    [Google Scholar]
  86. 86.
    Singer D. 1999. Neonatal tolerance to hypoxia: a comparative-physiological approach. Comp. Biochem. Physiol. A 123:3221–34
    [Google Scholar]
  87. 87.
    Peterson BL, Park TJ, Larson J. 2012. Adult naked mole-rat brain retains the NMDA receptor subunit GluN2D associated with hypoxia tolerance in neonatal mammals. Neurosci. Lett. 506:2342–45
    [Google Scholar]
  88. 88.
    Bickler PE, Fahlman CS, Taylor DM. 2003. Oxygen sensitivity of NMDA receptors: relationship to NR2 subunit composition and hypoxia tolerance of neonatal neurons. Neuroscience 118:125–35
    [Google Scholar]
  89. 89.
    Grimes KM, Barefield DY, Kumar M, McNamara JW, Weintraub ST et al. 2017. The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent. Pflügers Arch 469:121603–13
    [Google Scholar]
  90. 90.
    Bigham AW, Lee FS. 2014. Human high-altitude adaptation: forward genetics meets the HIF pathway. Genes Dev 28:202189–204
    [Google Scholar]
  91. 91.
    Xiao B, Wang S, Yang G, Sun X, Zhao S et al. 2017. HIF-1α contributes to hypoxia adaptation of the naked mole rat. Oncotarget 8:66109941–51
    [Google Scholar]
  92. 92.
    Shams I, Avivi A, Nevo E. 2004. Hypoxic stress tolerance of the blind subterranean mole rat: expression of erythropoietin and hypoxia-inducible factor 1α. PNAS 101:269698–703
    [Google Scholar]
  93. 93.
    Ezzati M, Horwitz MEM, Thomas DSK, Friedman AB, Roach R et al. 2012. Altitude, life expectancy and mortality from ischaemic heart disease, stroke, COPD and cancers: national population-based analysis of US counties. J. Epidemiol. Commun. Health 66:7e17
    [Google Scholar]
  94. 94.
    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 278:17233355–63
    [Google Scholar]
  95. 95.
    Wu C-W, Storey KB. 2016. Life in the cold: links between mammalian hibernation and longevity. Biomol. Concepts 7:141–52
    [Google Scholar]
  96. 96.
    Edrey YH, Hanes M, Pinto M, Mele J, Buffenstein R. 2011. Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. ILAR J 52:141–53
    [Google Scholar]
  97. 97.
    Zhou X, Dou Q, Fan G, Zhang Q, Sanderford M et al. 2020. Beaver and naked mole rat genomes reveal common paths to longevity. Cell Rep 32:4107949
    [Google Scholar]
  98. 98.
    Horvath S, Haghani A, Macoretta N, Ablaeva J, Zoller JA et al. 2022. DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders. Nat. Aging 2:146–59
    [Google Scholar]
  99. 99.
    Zhang G, Cowled C, Shi Z, Huang Z, Bishop-Lilly KA et al. 2013. Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science 339:6118456–60
    [Google Scholar]
  100. 100.
    Tian X, Firsanov D, Zhang Z, Cheng Y, Luo L et al. 2019. SIRT6 is responsible for more efficient DNA double-strand break repair in long-lived species. Cell 177:3622–38.e22
    [Google Scholar]
  101. 101.
    Yamamura Y, Kawamura Y, Oiwa Y, Oka K, Onishi N et al. 2021. Isolation and characterization of neural stem/progenitor cells in the subventricular zone of the naked mole-rat brain. Inflamm. Regen. 41:31
    [Google Scholar]
  102. 102.
    Zhang L, Dong X, Tian X, Lee M, Ablaeva J et al. Maintenance of genome sequence integrity in long- and short-lived rodent species. Sci. Adv. 7:44eabj3284
    [Google Scholar]
  103. 103.
    Cagan A, Baez-Ortega A, Brzozowska N, Abascal F, Coorens THH et al. 2022. Somatic mutation rates scale with lifespan across mammals. Nature 604:7906517–24
    [Google Scholar]
  104. 104.
    Lewis KN, Andziak B, Yang T, Buffenstein R 2013. The naked mole-rat response to oxidative stress: Just deal with it. Antioxid. Redox Signal. 19:121388–99
    [Google Scholar]
  105. 105.
    Andziak B, O'Connor TP, Qi W, DeWaal EM, Pierce A et al. 2006. High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell 5:6463–71
    [Google Scholar]
  106. 106.
    Andziak B, O'Connor TP, Buffenstein R 2005. Antioxidants do not explain the disparate longevity between mice and the longest-living rodent, the naked mole-rat. Mech. Ageing Dev. 126:111206–12
    [Google Scholar]
  107. 107.
    Kasaikina MV, Lobanov AV, Malinouski MY, Lee BC, Seravalli J et al. 2011. Reduced utilization of selenium by naked mole rats due to a specific defect in GPx1 expression. J. Biol. Chem. 286:1917005–14
    [Google Scholar]
  108. 108.
    Salmon AB, Akha AAS, Buffenstein R, Miller RA. 2008. Fibroblasts from naked mole-rats are resistant to multiple forms of cell injury, but sensitive to peroxide, ultraviolet light, and endoplasmic reticulum stress. J. Gerontol. A 63:3232–41
    [Google Scholar]
  109. 109.
    Takasugi M, Firsanov D, Tombline G, Ning H, Ablaeva J et al. 2020. Naked mole-rat very-high-molecular-mass hyaluronan exhibits superior cytoprotective properties. Nat. Commun. 11:12376
    [Google Scholar]
  110. 110.
    Vyssokikh MY, Holtze S, Averina OA, Lyamzaev KG, Panteleeva AA et al. 2020. Mild depolarization of the inner mitochondrial membrane is a crucial component of an anti-aging program. PNAS 117:126491–501
    [Google Scholar]
  111. 111.
    Lewis KN, Wason E, Edrey YH, Kristan DM, Nevo E, Buffenstein R. 2015. Regulation of Nrf2 signaling and longevity in naturally long-lived rodents. PNAS 112:123722–27
    [Google Scholar]
  112. 112.
    López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. 2013. The hallmarks of aging. Cell 153:61194–217
    [Google Scholar]
  113. 113.
    Pérez VI, Buffenstein R, Masamsetti V, Leonard S, Salmon AB et al. 2009. Protein stability and resistance to oxidative stress are determinants of longevity in the longest-living rodent, the naked mole-rat. PNAS 106:93059–64
    [Google Scholar]
  114. 114.
    Rodriguez KA, Osmulski PA, Pierce A, Weintraub ST, Gaczynska M, Buffenstein R. 2014. A cytosolic protein factor from the naked mole-rat activates proteasomes of other species and protects these from inhibition. Biochim. Biophys. Acta 1842:112060–72
    [Google Scholar]
  115. 115.
    Childs BG, Baker DJ, Kirkland JL, Campisi J, van Deursen JM. 2014. Senescence and apoptosis: Dueling or complementary cell fates?. EMBO Rep 15:111139–53
    [Google Scholar]
  116. 116.
    Muñoz-Espín D, Cañamero M, Maraver A, Gómez-López G, Contreras J et al. 2013. Programmed cell senescence during mammalian embryonic development. Cell 155:51104–18
    [Google Scholar]
  117. 117.
    Demaria M, Ohtani N, Youssef SA, Rodier F, Toussaint W et al. 2014. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev. Cell 31:6722–33
    [Google Scholar]
  118. 118.
    Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O et al. 2019. Cellular senescence: defining a path forward. Cell 179:4813–27
    [Google Scholar]
  119. 119.
    Gasek NS, Kuchel GA, Kirkland JL, Xu M. 2021. Strategies for targeting senescent cells in human disease. Nat. Aging 1:10870–79
    [Google Scholar]
  120. 120.
    Seluanov A, Hine C, Bozzella M, Hall A, Sasahara THC et al. 2008. Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan. Aging Cell 7:6813–23
    [Google Scholar]
  121. 121.
    Zhao Y, Tyshkovskiy A, Muñoz-Espín D, Tian X, Serrano M et al. 2018. Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence. PNAS 115:81801–6
    [Google Scholar]
  122. 122.
    Chee W-Y, Kurahashi Y, Kim J, Miura K, Okuzaki D et al. 2021. β-Catenin-promoted cholesterol metabolism protects against cellular senescence in naked mole-rat cells. Commun. Biol. 4:357
    [Google Scholar]
  123. 123.
    Franceschi C, Campisi J. 2014. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A 69:Suppl. 1S4–9
    [Google Scholar]
  124. 124.
    Hilton HG, Rubinstein ND, Janki P, Ireland AT, Bernstein N et al. 2019. Single-cell transcriptomics of the naked mole-rat reveals unexpected features of mammalian immunity. PLOS Biol 17:11e3000528
    [Google Scholar]
  125. 125.
    Emmrich S, Trapp A, Tolibzoda Zakusilo F, Straight ME, Ying AK et al. 2022. Characterization of naked mole-rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits. EMBO J 41:15e109694
    [Google Scholar]
  126. 126.
    Emmrich S, Tolibzoda Zakusilo F, Trapp A, Zhou X, Zhang Q et al. 2021. Ectopic cervical thymi and no thymic involution until midlife in naked mole rats. Aging Cell 20:10e13477
    [Google Scholar]
  127. 127.
    Delaney MA, Nagy L, Kinsel MJ, Treuting PM. 2013. Spontaneous histologic lesions of the adult naked mole rat (Heterocephalus glaber): a retrospective survey of lesions in a zoo population. Vet. Pathol. 50:4607–21
    [Google Scholar]
  128. 128.
    Delaney MA, Ward JM, Walsh TF, Chinnadurai SK, Kerns K et al. 2016. Initial case reports of cancer in naked mole-rats (Heterocephalus glaber). Vet. Pathol. 53:3691–96
    [Google Scholar]
  129. 129.
    Taylor KR, Milone NA, Rodriguez CE. 2017. Four cases of spontaneous neoplasia in the naked mole-rat (Heterocephalus glaber), a putative cancer-resistant species. J. Gerontol. A 72:138–43
    [Google Scholar]
  130. 130.
    Cole JE, Steeil JC, Sarro SJ, Kerns KL, Cartoceti A. 2020. Chordoma of the sacrum of an adult naked mole-rat. J. Vet. Diagn. Investig. 32:1132–35
    [Google Scholar]
  131. 131.
    Schreiber TH, Podack ER. 2009. A critical analysis of the tumour immunosurveillance controversy for 3-MCA-induced sarcomas. Br. J. Cancer 101:3381–86
    [Google Scholar]
  132. 132.
    Abel EL, Angel JM, Kiguchi K, DiGiovanni J. 2009. Multi-stage chemical carcinogenesis in mouse skin: fundamentals and applications. Nat. Protoc. 4:91350–62
    [Google Scholar]
  133. 133.
    Hadi F, Smith ESJ, Khaled WT 2021. Naked mole-rats: Resistant to developing cancer or good at avoiding it?. The Extraordinary Biology of the Naked Mole-Rat R Buffenstein, TJ Park, MM Holmes 341–52 Cham, Switz.: Springer Nat.
    [Google Scholar]
  134. 134.
    DiGiovanni J. 1992. Multistage carcinogenesis in mouse skin. Pharmacol. Ther. 54:163–128
    [Google Scholar]
  135. 135.
    Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:5646–74
    [Google Scholar]
  136. 136.
    Hoste E, Arwert EN, Lal R, South AP, Salas-Alanis JC et al. 2015. Innate sensing of microbial products promotes wound-induced skin cancer. Nat. Commun. 6:5932
    [Google Scholar]
  137. 137.
    Bald T, Quast T, Landsberg J, Rogava M, Glodde N et al. 2014. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507:7490109–13
    [Google Scholar]
  138. 138.
    Mittal D, Saccheri F, Vénéreau E, Pusterla T, Bianchi ME, Rescigno M. 2010. TLR4-mediated skin carcinogenesis is dependent on immune and radioresistant cells. EMBO J 29:132242–52
    [Google Scholar]
  139. 139.
    Choi ME, Price DR, Ryter SW, Choi AMK. 2019. Necroptosis: a crucial pathogenic mediator of human disease. JCI Insight 4:15e128834
    [Google Scholar]
  140. 140.
    Seluanov A, Hine C, Azpurua J, Feigenson M, Bozzella M et al. 2009. Hypersensitivity to contact inhibition provides a clue to cancer resistance of naked mole-rat. PNAS 106:4619352–57
    [Google Scholar]
  141. 141.
    Liang S, Mele J, Wu Y, Buffenstein R, Hornsby PJ. 2010. Resistance to experimental tumorigenesis in cells of a long-lived mammal, the naked mole-rat (Heterocephalus glaber). Aging Cell 9:4626–35
    [Google Scholar]
  142. 142.
    Hadi F, Kulaberoglu Y, Lazarus KA, Bach K, Ugur R et al. 2020. Transformation of naked mole-rat cells. Nature 583:7814E1–7
    [Google Scholar]
  143. 143.
    Deuker MM, Lewis KN, Ingaramo M, Kimmel J, Buffenstein R, Settleman J. 2020. Unprovoked stabilization and nuclear accumulation of the naked mole-rat p53 protein. Sci. Rep. 10:16966
    [Google Scholar]
  144. 144.
    Manov I, Hirsh M, Iancu TC, Malik A, Sotnichenko N et al. 2013. Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence. BMC Biol 11:91
    [Google Scholar]
  145. 145.
    Altwasser R, Paz A, Korol A, Manov I, Avivi A, Shams I. 2019. The transcriptome landscape of the carcinogenic treatment response in the blind mole rat: insights into cancer resistance mechanisms. BMC Genom 20:17
    [Google Scholar]
  146. 146.
    Gorbunova V, Hine C, Tian X, Ablaeva J, Gudkov AV et al. 2012. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism. PNAS 109:4719392–96
    [Google Scholar]
  147. 147.
    Caulin AF, Maley CC. 2011. Peto's paradox: evolution's prescription for cancer prevention. Trends Ecol. Evol. 26:4175–82
    [Google Scholar]
  148. 148.
    Sulak M, Fong L, Mika K, Chigurupati S, Yon L et al. 2016. TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. elife 5:e11994
    [Google Scholar]
  149. 149.
    Vazquez JM, Sulak M, Chigurupati S, Lynch VJ. 2018. A zombie LIF gene in elephants is upregulated by TP53 to induce apoptosis in response to DNA damage. Cell Rep 24:71765–76
    [Google Scholar]
  150. 150.
    Tollis M, Ferris E, Campbell MS, Harris VK, Rupp SM et al. 2021. Elephant genomes reveal accelerated evolution in mechanisms underlying disease defenses. Mol. Biol. Evol. 38:93606–20
    [Google Scholar]
  151. 151.
    Roellig K, Drews B, Goeritz F, Hildebrandt TB. 2011. The long gestation of the small naked mole-rat (Heterocephalus glaber RÜPPELL, 1842) studied with ultrasound biomicroscopy and 3D-ultrasonography. PLOS ONE 6:3e17744
    [Google Scholar]
/content/journals/10.1146/annurev-animal-050322-074744
Loading
/content/journals/10.1146/annurev-animal-050322-074744
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error