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Biogerontology

, Volume 17, Issue 2, pp 421–429 | Cite as

The somatotropic axis may not modulate ageing and longevity in humans

  • Éric Le BourgEmail author
Opinion Article

Abstract

Studies in nematodes and mice have shown that the somatotropic axis can modulate their longevity and it has been argued that it could also modulate human longevity. Thus, like nematodes and mice, human beings should live longer when facing starvation and genetic variation of the somatotropic axis should be linked to longevity. This article argues that, because the life-history strategies of humans are very different from those of mice, these hypotheses are not warranted.

Keywords

Somatotropic axis IGF-1 Growth hormone Life history strategies Longevity Ageing 

Notes

Acknowledgments

Many thanks are due to Simon Galas, University of Montpellier, France, and to anonymous referees for their helpful comments.

References

  1. Aguiar-Oliveira MH, Oliveira FT, Pereira RM, Oliveira CR, Black- ford A, Valenca EH, Santos EG, Gois-Junior MB, Meneguz-Moreno RA, Araujo VP, Oliveira-Neto LA, Almeida RP, Santos MA, Farias NT, Silveira DC, Cabral GW, Calazans FR, Seabra JD, Lopes TF, Rodrigues EO, Porto LA, Oliveira IP, Melo EV, Martari M, Salvatori R (2010) Longevity in untreated congenital growth hormone deficiency due to a homozygous mutation in the GHRH receptor gene. J Clin Endocrinol Metab 95:714–721CrossRefPubMedPubMedCentralGoogle Scholar
  2. Austad SN (2012) Mixed results for dieting monkeys. Nature 489:210–211PubMedGoogle Scholar
  3. Bao JM, Song XL, Hong YQ, Zhu HL, Li C, Zhang T, Chen W, Zhao SC, Chen Q (2014) Association between FOXO3A gene polymorphisms and human longevity: a meta-analysis. Asian J Androl 16:446–452CrossRefPubMedPubMedCentralGoogle Scholar
  4. Barbieri M, Bonafè M, Franceschi C, Paolisso G (2003) Insulin/IGF-1 signaling pathway: an evolutionary conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab 285:E1064–E1071CrossRefPubMedGoogle Scholar
  5. Bartke A (2005) Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinol 146:3718–3723CrossRefGoogle Scholar
  6. Bartke A, Sun LY, Longo V (2013) Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev 93:571–598CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bertrand HA, Herlihy JT, Ikeno Y, Yu BP (1999) Dietary restriction. In: Yu BP (ed) Methods in Aging Research. CRC Press, Boca Raton, pp 271–300Google Scholar
  8. Besson A, Salemi S, Gallati S, Jenal A, Horn R, Mullis PS, Mullis PE (2003) Reduced longevity in untreated patients with isolated growth hormone deficiency. J Clin Endocrinol Metab 88:3364–3367CrossRefGoogle Scholar
  9. Braeckman BP, Demetrius L, Vanfleteren J (2006) The dietary restriction in C. elegans and humans: is the worm a one-millimeter human? Biogerontology 7:127–133CrossRefPubMedGoogle Scholar
  10. Cava E, Fontana L (2013) Will calorie restriction work in humans? Aging (Albany NY) 5:507–514CrossRefGoogle Scholar
  11. Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L (2001) Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science 292:104–106CrossRefPubMedGoogle Scholar
  12. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325:201–224CrossRefPubMedPubMedCentralGoogle Scholar
  13. Colman RJ, Beasley TM, Kemnitz JW, Johnson SC, Weindruch R, Anderson RM (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun 5:3557CrossRefPubMedPubMedCentralGoogle Scholar
  14. de Cabo R, Carmona-Gutierrez D, Bernier M, Hall MN, Madeo F (2014) The search for antiaging interventions: from elixirs to fasting regimens. Cell 157:1515–1526CrossRefPubMedPubMedCentralGoogle Scholar
  15. de Grey ADNJ (2005) The unfortunate influence of the weather on the rate of ageing: why human caloric restriction or its emulation may only extend life expectancy by 2–3 years. Gerontology 51:73–82CrossRefPubMedGoogle Scholar
  16. Demetrius L (2005) Of mice and men. When it comes to studying ageing and the means to slow it down, mice are not just small humans. EMBO Rep 6:S39–S44CrossRefPubMedPubMedCentralGoogle Scholar
  17. Flachsbart F, Caliebe A, Kleindorp R, Blanché H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA 106:2700–2705CrossRefPubMedPubMedCentralGoogle Scholar
  18. Fontana L, Colman RJ, Holloszy JO, Weindruch R (2011) Calorie restriction in nonhuman and human primates. In: Masoro EJ, Austad SN (eds) Handbook of the biology of aging, 7th edn. Academic press, San Diego, pp 447–462CrossRefGoogle Scholar
  19. Friedman DB, Johnson TE (1988) Three mutants that extend both mean and maximum lifespan of the nematode, Caenorhabditis elegans, define the age-1 gene. J Gerontol Biol Sci 43:B102–B109CrossRefGoogle Scholar
  20. Galis F, Van der Sluijs I, Van Dooren TJM, Metz JAJ, Nussbaumer M (2007) Do large dogs die young? J Exp Zool (Mol Dev Evol) 308b:119–126CrossRefGoogle Scholar
  21. Gavrilova NS, Gavrilov LA (2012) Comments on dietary restriction, Okinawa diet and longevity. Gerontology 58:221–223CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hallengren E, Almgren P, Engström G, Hedblad B, Persson M, Suhr M, Bergmann A, Melander O (2014) Fasting levels of high-sensitivity growth hormone predict cardiovascular morbidity and mortality: the Malmö Diet and cancer study. J Am Coll Cardiol 64:1452–1460CrossRefPubMedPubMedCentralGoogle Scholar
  23. He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, Rodriguez B, Chen R, Donlon TA, Willcox DC, Willcox B (2014) Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. PLoS ONE 9:e94385CrossRefPubMedPubMedCentralGoogle Scholar
  24. Heidler T, Hartwig K, Daniel H, Wenzel U (2010) Caenorhabditis elegans lifespan extension caused by treatment with an orally active ROS-generator is dependent on DAF-16 and SIR-2.1. Biogerontology 11:183–195CrossRefPubMedGoogle Scholar
  25. Holliday R (1989) Food reproduction and longevity: is the extended lifespan of calorie-restricted animals an evolutionary adaptation? BioEssays 10:125–127CrossRefPubMedGoogle Scholar
  26. Holzenberger M, Martin-Crespo RM, Vicent D, Ruiz-Torres A (1991) Decelerated growth and longevity in men. Arch Gerontol Geriatr 13:89–101CrossRefPubMedGoogle Scholar
  27. Hunt PR, Son TG, Wilson MA, Yu QS, Wood WH, Zhang Y, Becker KG, Greig NH, Mattson MP, Camandola S, Wolkow CA (2011) Extension of lifespan in C. elegans by naphthoquinones that act through stress hormesis mechanisms. PLoS ONE 6(7):e21922CrossRefPubMedPubMedCentralGoogle Scholar
  28. Kaeberlein TL, Smith ED, Tsuchiya M, Welton KL, Thomas JH, Fields S, Kennedy BK, Kaeberlein M (2006) Lifespan extension in Caenorhabditis elegans by complete removal of food. Aging Cell 5:487–494CrossRefPubMedGoogle Scholar
  29. Kemkes-Grottenthaler A (2005) The short die young: the interrelationship between stature and longevity—evidence from skeletal remains. Am J Physiol Anthropol 128:340–347CrossRefGoogle Scholar
  30. Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512CrossRefPubMedGoogle Scholar
  31. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366:461–464CrossRefPubMedGoogle Scholar
  32. Klass MR (1983) A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 22:279–286CrossRefPubMedGoogle Scholar
  33. Klass MR, Hirsh D (1976) Non-ageing developmental variant of Caenorhabditis elegans. Nature 260:523–525CrossRefPubMedGoogle Scholar
  34. Kraus C, Pavard S, Promislow DEL (2013) The size-life span trade-off decomposed: why large dogs die young. Am Nat 181:492–505CrossRefPubMedGoogle Scholar
  35. Kržišnik C, Grgurić S, Cvijović K, Laron Z (2010) Longevity of the hypopituitary patients from the island Krk: a follow-up study. Pediatr Endocrinol Rev 7:357–362PubMedGoogle Scholar
  36. Le Bourg E (2005) Calorie restriction to retard aging and increase longevity. Presse Méd 34:121–127CrossRefPubMedGoogle Scholar
  37. Le Bourg E (2006) Dietary restriction would probably not increase longevity in human beings and other species able to leave unsuitable environments. Biogerontology 7:149–152CrossRefPubMedGoogle Scholar
  38. Le Bourg E (2010) Predicting whether dietary restriction would increase longevity in species not tested so far. Ageing Res Rev 9:289–297CrossRefPubMedGoogle Scholar
  39. Le Bourg E (2012a) Dietary restriction studies in humans: focusing on obesity, forgetting longevity. Gerontology 58:126–128CrossRefPubMedGoogle Scholar
  40. Le Bourg E (2012b) Dietary restriction in humans: a response to Drs Gavrilova and Gavrilov. Gerontology 58:224–226CrossRefGoogle Scholar
  41. Le Bourg E (2013) Obsolete ideas and logical confusions can be obstacles for biogerontology research. Biogerontology 14:221–227CrossRefPubMedGoogle Scholar
  42. Maison P, Balkau B, Simon D, Chanson P, Rosselin G, Eschwege E (1998) Growth hormone as a risk for premature mortality in healthy subjects: data from the Paris prospective study. Br Med J 316:1132–1133CrossRefGoogle Scholar
  43. Mattison JA, Roth GS, Beasley TM, Tilmont EM, Handy AM, Herbert RL, Longo DL, Allison DB, Young JE, Bryant M, Barnard D, Ward WF, Qi W, Ingram DK, de Cabo R (2012) Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489:318–321CrossRefPubMedGoogle Scholar
  44. Miller DL, Roth MB (2007) Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci USA 104:20618–20622CrossRefPubMedPubMedCentralGoogle Scholar
  45. Milman S, Atzmon G, Huffman DM, Wan J, Crandall JP, Cohen P, Barzilai N (2014) Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell 13:769–771CrossRefPubMedPubMedCentralGoogle Scholar
  46. Nakagawa S, Lagisz M, Hector KL, Spencer HG (2012) Comparative and meta-analytic insights into life extension via dietary restriction. Aging Cell 11:401–409CrossRefPubMedGoogle Scholar
  47. Nygaard M, Lindahl-Jacobsen R, Soerensen M, Mengel-From J, Andersen-Ranberg K, Jeune B, Vaupel JW, Tan Q, Christiansen L, Christensen K (2014) Birth cohort differences in the prevalence of longevity-associated variants in APOE and FOXO3A in Danish long-lived individuals. Exp Gerontol 57:41–46CrossRefPubMedGoogle Scholar
  48. Passtoors WM, Beekman M, Deelen J, van der Breggen R, Maier AB, Guigas B, Derhovanessian E, van Heemst D, de Craen AJ, Gunn DA, Pawelec G, Slagboom PE (2013) Gene expression analysis of mTOR pathway: association with human longevity. Aging Cell 12:24–31CrossRefPubMedGoogle Scholar
  49. Phelan JP, Austad SN (1989) natural selection, dietary restriction, and extended longevity. Growth Dev Aging 53:4–6PubMedGoogle Scholar
  50. Phelan JP, Rose MR (2005) Why dietary restriction substantially increases longevity in animal models but won’t in humans. Ageing Res Rev 4:339–350CrossRefPubMedGoogle Scholar
  51. Pianka ER (1970) On r and K selection. Am Nat 102:592–597CrossRefGoogle Scholar
  52. Piper MD, Partridge L, Raubenheimer D, Simpson SJ (2011) Dietary restriction and aging: a unifying perspective. Cell Metab 14:154–160CrossRefPubMedPubMedCentralGoogle Scholar
  53. Puig O, Mattila J (2011) Understanding Forkhead box class O function: lessons from Drosophila melanogaster. Antioxid Redox Signal 14:635–647CrossRefPubMedGoogle Scholar
  54. Redman LM, Ravussin E (2011) Caloric restriction in humans: impact on physiological, psychological, and behavioral outcomes. Antioxid Redox Signal 14:275–287CrossRefPubMedPubMedCentralGoogle Scholar
  55. Salaris L, Poulain M, Samaras TT (2012) Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866–2006. Biodemogr Soc Biol 58:1–13CrossRefGoogle Scholar
  56. Shadyab AH, LaCroix AZ (2015) Genetic factors associated with longevity: a review of recent findings. Ageing Res Rev 19:1–7CrossRefPubMedGoogle Scholar
  57. Shanley DP, Kirkwood TBL (2006) Caloric restriction does not enhance longevity in all species and is unlikely to do so in humans. Biogerontology 7:165–168CrossRefPubMedGoogle Scholar
  58. Soerensen M, Dato S, Christensen K, McGue M, Stevnsner T, Bohr VA, Christiansen L (2010) Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging Cell 9:1010–1017CrossRefPubMedPubMedCentralGoogle Scholar
  59. Soerensen M, Dato S, Tan Q, Thinggaard M, Kleindorp R, Beekman M, Jacobsen R, Suchiman HE, de Craen AJ, Westendorp RG, Schreiber S, Stevnsner T, Bohr VA, Slagboom PE, Nebel A, Vaupel JW, Christensen K, McGue M, Christiansen L (2012) Human longevity and variation in GH/IGF-1/insulin signaling, DNA damage signaling and repair and pro/antioxidant pathway genes: cross sectional and longitudinal studies. Exp Gerontol 47:379–387CrossRefPubMedPubMedCentralGoogle Scholar
  60. Soerensen M, Nygaard M, Dato S, Stevnsner T, Bohr VA, Christensen K, Christiansen L (2015) Association study of FOXO3A SNPs and aging phenotypes in Danish oldest-old individuals. Aging Cell 14:60–66CrossRefPubMedPubMedCentralGoogle Scholar
  61. Stearns SC (1983) The influence of size and phylogeny on patterns of covariation among life-history traits in the mammals. Oikos 41:173–187CrossRefGoogle Scholar
  62. Stewart ST, Cutler DM, Rosen AB (2009) Forecasting the effects of obesity and smoking on U.S. life expectancy. N Engl J Med 361:2252–2260CrossRefPubMedPubMedCentralGoogle Scholar
  63. Swindell WR (2012) Dietary restriction in rats and mice: a meta-analysis and review of the evidence for genotype-dependent effects on lifespan. Ageing Res Rev 11:254–270CrossRefPubMedPubMedCentralGoogle Scholar
  64. Van Voorhies WA, Fuchs J, Thomas S (2005) The longevity of Caenorhabditis elegans in soil. Biol Lett 1:247–249CrossRefPubMedPubMedCentralGoogle Scholar
  65. Wade N (2009) Dieting monkeys offer hope for living longer. New York Times, New York edition, page A1. http://www.nytimes.com/2009/07/10/science/10aging.html
  66. Walford RL, Mock D, Verdery R, MacCallum T (2002) Calorie restriction in Biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J Geront Biol Sci 57A:B211–B224CrossRefGoogle Scholar
  67. Willcox DC, Willcox BJ, Todoriki H, Curb JD, Suzuki M (2006) Caloric restriction and human longevity: what can we learn from the Okinawans? Biogerontology 7:173–177CrossRefPubMedGoogle Scholar
  68. Ziv E, Hu D (2011) Genetic variation in insulin/IGF-1 signaling pathways and longevity. Ageing Res Rev 10:201–204CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2015

Authors and Affiliations

  1. 1.Centre de Recherches sur la Cognition Animale, Centre de Biologie IntégrativeUniversité de Toulouse, CNRS, UPSToulouseFrance

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