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Can aging be 'drugged'?

Abstract

The engines that drive the complex process of aging are being identified by model-organism research, thereby providing potential targets and rationale for drug studies. Several studies of small molecules have already been completed in animal models with the hope of finding an elixir for aging, with a few compounds showing early promise. What lessons can we learn from drugs currently being tested, and which pitfalls can we avoid in our search for a therapeutic for aging? Finally, we must also ask whether an elixir for aging would be applicable to everyone, or whether we age differently, thus potentially shortening lifespan in some individuals.

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References

  1. Rowe, J.W. & Kahn, R.L. Successful aging. Gerontologist 37, 433–440 (1997).

    CAS  PubMed  Article  Google Scholar 

  2. Kennedy, B.K. et al. Geroscience: linking aging to chronic disease. Cell 159, 709–713 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  3. Salvioli, S. et al. Immune system, cell senescence, aging and longevity–inflamm-aging reappraised. Curr. Pharm. Des. 19, 1675–1679 (2013).

    CAS  PubMed  Google Scholar 

  4. Miller, R.A. et al. An Aging Interventions Testing Program: study design and interim report. Aging Cell 6, 565–575 (2007).

    CAS  PubMed  Article  Google Scholar 

  5. Harrison, D.E. et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460, 392–395 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. Miller, R.A. et al. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J. Gerontol. A Biol. Sci. Med. Sci. 66, 191–201 (2011).

    PubMed  Article  CAS  Google Scholar 

  7. Anisimov, V.N. et al. Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 10, 4230–4236 (2011).

    CAS  PubMed  Article  Google Scholar 

  8. Flynn, J.M. et al. Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell 12, 851–862 (2013).

    CAS  PubMed  Article  Google Scholar 

  9. Wilkinson, J.E. et al. Rapamycin slows aging in mice. Aging Cell 11, 675–682 (2012).

    CAS  PubMed  Article  Google Scholar 

  10. Tardif, S. et al. Testing efficacy of administration of the antiaging drug rapamycin in a nonhuman primate, the common marmoset. J. Gerontol. A Biol. Sci. Med. Sci. 70, 577–587 (2015).

    CAS  PubMed  Article  Google Scholar 

  11. Lamming, D.W. et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335, 1638–1643 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. Roy, J., Paquette, J.-S., Fortin, J.-F. & Tremblay, M.J. The immunosuppressant rapamycin represses human immunodeficiency virus type 1 replication. Antimicrob. Agents Chemother. 46, 3447–3455 (2002).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. Fang, Y. et al. Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab. 17, 456–462 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  14. Jagannath, C. & Bakhru, P. Rapamycin-induced enhancement of vaccine efficacy in mice. Methods Mol. Biol. 821, 295–303 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  15. Mannick, J. B. et al. mTOR inhibition improves immune function in the elderly. Sci. Transl. Med. 6, 268ra179 (2014).

    PubMed  Article  CAS  Google Scholar 

  16. Selman, C. et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326, 140–144 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  17. Wu, J.J. et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep. 4, 913–920 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  18. Tsai, S. et al. Muscle-specific 4E–BP1 signaling activation improves metabolic parameters during aging and obesity. J. Clin. Invest. 125, 2952–2964 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  19. Cornu, M., Albert, V. & Hall, M.N. mTOR in aging, metabolism, and cancer. Curr. Opin. Genet. Dev. 23, 53–62 (2013).

    CAS  PubMed  Article  Google Scholar 

  20. Campbell, R.K., White, J.R. & Saulie, B.A. Metformin: a new oral biguanide. Clin. Ther. 18, 360–371, discussion 359 (1996).

    CAS  PubMed  Article  Google Scholar 

  21. Bosi, E. Metformin–the gold standard in type 2 diabetes: what does the evidence tell us? Diabetes Obes. Metab. 11 Suppl 2, 3–8 (2009).

    CAS  PubMed  Article  Google Scholar 

  22. Martin-Montalvo, A. et al. Metformin improves healthspan and lifespan in mice. Nat. Commun. 4, 2192 (2013).

    PubMed  Article  CAS  Google Scholar 

  23. Andrzejewski, S., Gravel, S.-P., Pollak, M. & St-Pierre, J. Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab. 2, 12 (2014).

    PubMed  PubMed Central  Article  Google Scholar 

  24. Gandini, S. et al. Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev. Res. (Phila) 7, 867–885 (2014).

    CAS  Article  Google Scholar 

  25. Zhou, G. et al. Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167–1174 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. Cantó, C. et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 458, 1056–1060 (2009).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  27. Jäger, S., Handschin, C., St-Pierre, J. & Spiegelman, B.M. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1a. Proc. Natl. Acad. Sci. USA 104, 12017–12022 (2007).

    PubMed  Article  PubMed Central  CAS  Google Scholar 

  28. Mair, W. et al. Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB. Nature 470, 404–408 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  29. Apfeld, J., O'Connor, G., McDonagh, T., DiStefano, P.S. & Curtis, R. The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev. 18, 3004–3009 (2004).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  30. Greer, E.L. et al. An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. Curr. Biol. 17, 1646–1656 (2007).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  31. Viollet, B. et al. The AMP-activated protein kinase a2 catalytic subunit controls whole-body insulin sensitivity. J. Clin. Invest. 111, 91–98 (2003).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  32. Kobilo, T. et al. AMPK agonist AICAR improves cognition and motor coordination in young and aged mice. Learn. Mem. 21, 119–126 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. Kalender, A. et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 11, 390–401 (2010).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  34. Check Hayden, E. Anti-ageing pill pushed as bona fide drug. Nature 522, 265–266 (2015).

    CAS  PubMed  Article  Google Scholar 

  35. Howitz, K.T. et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425, 191–196 (2003).

    CAS  PubMed  Article  Google Scholar 

  36. Baur, J.A. et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337–342 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. Wood, J.G. et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430, 686–689 (2004).

    CAS  PubMed  Article  Google Scholar 

  38. Pearson, K.J. et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 8, 157–168 (2008).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  39. Jimenez-Gomez, Y. et al. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet. Cell Metab. 18, 533–545 (2013).

    CAS  PubMed  Article  Google Scholar 

  40. Fiori, J.L. et al. Resveratrol prevents b-cell dedifferentiation in nonhuman primates given a high-fat/high-sugar diet. Diabetes 62, 3500–3513 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  41. Mattison, J.A. et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489, 318–321 (2012).

    CAS  PubMed  Article  Google Scholar 

  42. Lagouge, M. et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1a. Cell 127, 1109–1122 (2006).

    CAS  PubMed  Article  Google Scholar 

  43. Sayin, O., Arslan, N. & Guner, G. The protective effects of resveratrol on human coronary artery endothelial cell damage induced by hydrogen peroxide in vitro. Acta Clin. Croat. 51, 227–235 (2012).

    PubMed  Google Scholar 

  44. Timmers, S. et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 14, 612–622 (2011).

    CAS  PubMed  Article  Google Scholar 

  45. Burnett, C. et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 477, 482–485 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  46. Kaeberlein, M. et al. Substrate-specific activation of sirtuins by resveratrol. J. Biol. Chem. 280, 17038–17045 (2005).

    CAS  PubMed  Article  Google Scholar 

  47. Beher, D. et al. Resveratrol is not a direct activator of SIRT1 enzyme activity. Chem. Biol. Drug Des. 74, 619–624 (2009).

    CAS  PubMed  Article  Google Scholar 

  48. Borra, M.T., Smith, B.C. & Denu, J.M. Mechanism of human SIRT1 activation by resveratrol. J. Biol. Chem. 280, 17187–17195 (2005).

    CAS  PubMed  Article  Google Scholar 

  49. Kulkarni, S.S. & Cantó, C. The molecular targets of resveratrol. Biochim. Biophys. Acta 1852, 1114–1123 (2015).

    CAS  PubMed  Article  Google Scholar 

  50. Woods, J.A., Wilund, K.R., Martin, S.A. & Kistler, B.M. Exercise, Inflammation and Aging. Aging Dis. 3, 130–140 (2012).

    PubMed  Google Scholar 

  51. Bruunsgaard, H. et al. A high plasma concentration of TNF-α is associated with dementia in centenarians. J. Gerontol. A Biol. Sci. Med. Sci. 54, M357–M364 (1999).

    CAS  PubMed  Article  Google Scholar 

  52. Bruunsgaard, H., Skinhøj, P., Pedersen, A.N., Schroll, M. & Pedersen, B.K. Ageing, tumour necrosis factor-alpha (TNF-α) and atherosclerosis. Clin. Exp. Immunol. 121, 255–260 (2000).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  53. Strong, R. et al. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7, 641–650 (2008).

    CAS  PubMed  Article  Google Scholar 

  54. Weiss, H.J. The discovery of the antiplatelet effect of aspirin: a personal reminiscence. J. Thromb. Haemost. 1, 1869–1875 (2003).

    CAS  PubMed  Article  Google Scholar 

  55. Shoelson, S.E., Lee, J. & Goldfine, A.B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793–1801 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  56. Koska, J. et al. The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study. Diabetologia 52, 385–393 (2009).

    CAS  PubMed  Article  Google Scholar 

  57. Baron, S.H. Salicylates as hypoglycemic agents. Diabetes Care 5, 64–71 (1982).

    CAS  PubMed  Article  Google Scholar 

  58. Goldfine, A.B. et al. Salicylate (salsalate) in patients with type 2 diabetes: a randomized trial. Ann. Intern. Med. 159, 1–12 (2013).

    PubMed  PubMed Central  Article  Google Scholar 

  59. Yuan, M. et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ. Science 293, 1673–1677 (2001).

    CAS  PubMed  Article  Google Scholar 

  60. Zhang, G. et al. Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 497, 211–216 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  61. Melnyk, A. & Himms-Hagen, J. Resistance to aging-associated obesity in capsaicin-desensitized rats one year after treatment. Obes. Res. 3, 337–344 (1995).

    CAS  PubMed  Article  Google Scholar 

  62. Riera, C.E. et al. TRPV1 pain receptors regulate longevity and metabolism by neuropeptide signaling. Cell 157, 1023–1036 (2014).

    CAS  PubMed  Article  Google Scholar 

  63. Park, T.J. et al. Selective inflammatory pain insensitivity in the African naked mole-rat (Heterocephalus glaber). PLoS Biol. 6, e13 (2008).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  64. Kim, E.B. et al. Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479, 223–227 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  65. Bigal, M.E. & Walter, S. Monoclonal antibodies for migraine: preventing calcitonin gene-related peptide activity. CNS Drugs 28, 389–399 (2014).

    CAS  PubMed  Article  Google Scholar 

  66. Holzenberger, M. et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421, 182–187 (2003).

    CAS  PubMed  Article  Google Scholar 

  67. Xu, J. et al. Longevity effect of IGF-1R+/− mutation depends on genetic background-specific receptor activation. Aging Cell 13, 19–28 (2014).

    CAS  PubMed  Article  Google Scholar 

  68. Taguchi, A., Wartschow, L.M. & White, M.F. Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science 317, 369–372 (2007).

    CAS  PubMed  Article  Google Scholar 

  69. Selman, C. et al. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J. 22, 807–818 (2008).

    CAS  PubMed  Article  Google Scholar 

  70. Blüher, M. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299, 572–574 (2003).

    PubMed  Article  CAS  Google Scholar 

  71. Foukas, L.C. et al. Long-term p110a PI3K inactivation exerts a beneficial effect on metabolism. EMBO Mol. Med. 5, 563–571 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  72. Ortega-Molina, A. et al. Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab. 15, 382–394 (2012).

    CAS  PubMed  Article  Google Scholar 

  73. Nojima, A. et al. Haploinsufficiency of Akt1 prolongs the lifespan of mice. PLoS ONE 8, e69178 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. Brown-Borg, H.M., Borg, K.E., Meliska, C.J. & Bartke, A. Dwarf mice and the ageing process. Nature 384, 33 (1996).

    CAS  PubMed  Article  Google Scholar 

  75. Flurkey, K., Papaconstantinou, J., Miller, R.A. & Harrison, D.E. Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc. Natl. Acad. Sci. USA 98, 6736–6741 (2001).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  76. Flurkey, K., Papaconstantinou, J. & Harrison, D.E. The Snell dwarf mutation Pit1dw can increase life span in mice. Mech. Ageing Dev. 123, 121–130 (2002).

    CAS  PubMed  Article  Google Scholar 

  77. Coschigano, K.T., Clemmons, D., Bellush, L.L. & Kopchick, J.J. Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141, 2608–2613 (2000).

    CAS  PubMed  Article  Google Scholar 

  78. Sun, L. Y. et al. Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. eLife 2, e01098 (2013).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  79. Zhang, Y. et al. The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. ELife Sci. 1, e00065 (2012).

    Article  CAS  Google Scholar 

  80. Kurosu, H. et al. Suppression of aging in mice by the hormone klotho. Science 309, 1829–1833 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  81. Kuro-o, M. et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45–51 (1997).

    CAS  PubMed  Article  Google Scholar 

  82. Shiozaki, M. et al. Morphological and biochemical signs of age-related neurodegenerative changes in klotho mutant mice. Neuroscience 152, 924–941 (2008).

    CAS  PubMed  Article  Google Scholar 

  83. Potthoff, M.J., Kliewer, S.A. & Mangelsdorf, D.J. Endocrine fibroblast growth factors 15/19 and 21: from feast to famine. Genes Dev. 26, 312–324 (2012).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  84. Yie, J. et al. FGF21 N- and C-termini play different roles in receptor interaction and activation. FEBS Lett. 583, 19–24 (2009).

    CAS  PubMed  Article  Google Scholar 

  85. Conover, C.A. PAPP-A: a new anti-aging target? Aging Cell 9, 942–946 (2010).

    CAS  PubMed  Article  Google Scholar 

  86. Conover, C.A. & Bale, L.K. Loss of pregnancy-associated plasma protein A extends lifespan in mice. Aging Cell 6, 727–729 (2007).

    CAS  PubMed  Article  Google Scholar 

  87. Conover, C.A. et al. Longevity and age-related pathology of mice deficient in pregnancy-associated plasma protein-A. J. Gerontol. A Biol. Sci. Med. Sci. 65, 590–599 (2010).

    PubMed  Article  CAS  Google Scholar 

  88. Harrington, S.C., Simari, R.D. & Conover, C.A. Genetic deletion of pregnancy-associated plasma protein-A Is associated with resistance to atherosclerotic lesion development in apolipoprotein E–deficient mice challenged with a high-fat diet. Circ. Res. 100, 1696–1702 (2007).

    CAS  PubMed  Article  Google Scholar 

  89. Tanner, S.J., Hefferan, T.E., Rosen, C.J. & Conover, C.A. Impact of pregnancy-associated plasma protein-A deletion on the adult murine skeleton. J. Bone Miner. Res. 23, 655–662 (2008).

    CAS  PubMed  Article  Google Scholar 

  90. Adams, A.C. et al. LY2405319, an engineered FGF21 variant, improves the metabolic status of diabetic monkeys. PLoS ONE 8, e65763 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  91. Gaich, G. et al. The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes. Cell Metab. 18, 333–340 (2013).

    CAS  PubMed  Article  Google Scholar 

  92. Smith, R. et al. FGF21 can be mimicked in vitro and in vivo by a novel anti-FGFR1c/β-klotho bispecific protein. PLoS ONE 8, e61432 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  93. Johnson, J.E. & Johnson, F.B. Methionine restriction activates the retrograde response and confers both stress tolerance and lifespan extension to yeast, mouse and human cells. PLoS ONE 9, e97729 (2014).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  94. Cabreiro, F. et al. Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153, 228–239 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  95. Grandison, R.C., Piper, M.D.W. & Partridge, L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462, 1061–1064 (2009).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  96. Miller, R.A. et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4, 119–125 (2005).

    CAS  PubMed  Article  Google Scholar 

  97. Richie, J.P. et al. Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J. 8, 1302–1307 (1994).

    CAS  PubMed  Article  Google Scholar 

  98. Komninou, D., Leutzinger, Y., Reddy, B.S. & Richie, J.P. Jr. Methionine restriction inhibits colon carcinogenesis. Nutr. Cancer 54, 202–208 (2006).

    CAS  PubMed  Article  Google Scholar 

  99. McCarty, M.F., Barroso-Aranda, J. & Contreras, F. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med. Hypotheses 72, 125–128 (2009).

    CAS  PubMed  Article  Google Scholar 

  100. Kabil, H., Kabil, O., Banerjee, R., Harshman, L.G. & Pletcher, S.D. Increased transsulfuration mediates longevity and dietary restriction in Drosophila. Proc. Natl. Acad. Sci. USA 108, 16831–16836 (2011).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  101. Hine, C. et al. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell 160, 132–144 (2015).

    CAS  PubMed  Article  Google Scholar 

  102. Miller, D.L. & Roth, M.B. Hydrogen sulfide increases thermotolerance and lifespan in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA 104, 20618–20622 (2007).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  103. Ali, M.Y. et al. Regulation of vascular nitric oxide in vitro and in vivo; a new role for endogenous hydrogen sulphide? Br. J. Pharmacol. 149, 625–634 (2006).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  104. Marcolin, E. et al. Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis. Arq. Gastroenterol. 48, 72–79 (2011).

    PubMed  Article  Google Scholar 

  105. Weaver, I.C.G. et al. Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J. Neurosci. 25, 11045–11054 (2005).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. Liao, C.-Y., Johnson, T.E. & Nelson, J.F. Genetic variation in responses to dietary restriction—an unbiased tool for hypothesis testing. Exp. Gerontol. 48, 1025–1029 (2013).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  107. de Cabo, R., Carmona-Gutierrez, D., Bernier, M., Hall, M.N. & Madeo, F. The search for antiaging interventions: from elixirs to fasting regimens. Cell 157, 1515–1526 (2014).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  108. Walter, S. et al. A genome-wide association study of aging. Neurobiol. Aging 32, 2109.e15–28 (2011).

    PubMed  PubMed Central  Article  Google Scholar 

  109. Jeck, W.R., Siebold, A.P. & Sharpless, N.E. Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell 11, 727–731 (2012).

    CAS  PubMed  Article  Google Scholar 

  110. Willcox, B.J. et al. FOXO3A genotype is strongly associated with human longevity. Proc. Natl. Acad. Sci. USA 105, 13987–13992 (2008).

    CAS  PubMed  Article  PubMed Central  Google Scholar 

  111. Bollati, V. et al. Decline in genomic DNA methylation through aging in a cohort of elderly subjects. Mech. Ageing Dev. 130, 234–239 (2009).

    CAS  PubMed  Article  Google Scholar 

  112. Zampieri, M. et al. Reconfiguration of DNA methylation in aging. Mech. Ageing Dev. doi:10.1016/j.mad.2015.02.002 (20 February 2015).

  113. Lawton, K.A. et al. Analysis of the adult human plasma metabolome. Pharmacogenomics 9, 383–397 (2008).

    CAS  PubMed  Article  Google Scholar 

  114. Zapata, H.J. & Quagliarello, V.J. The microbiota and microbiome in aging: potential implications in health and age-related diseases. J. Am. Geriatr. Soc. 63, 776–781 (2015).

    PubMed  PubMed Central  Article  Google Scholar 

  115. Tilg, H. & Kaser, A. Gut microbiome, obesity, and metabolic dysfunction. J. Clin. Invest. 121, 2126–2132 (2011).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  116. Xue, Q.-L., Bandeen-Roche, K., Varadhan, R., Zhou, J. & Fried, L.P. Initial Manifestations of frailty criteria and the development of frailty phenotype in the Women's Health and Aging Study II. J. Gerontol. A Biol. Sci. Med. Sci. 63, 984–990 (2008).

    PubMed  Article  Google Scholar 

  117. Rowe, J.W., Minaker, K.L., Pallotta, J.A. & Flier, J.S. Characterization of the insulin resistance of aging. J. Clin. Invest. 71, 1581–1587 (1983).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  118. Fink, R.I., Kolterman, O.G., Griffin, J. & Olefsky, J.M. Mechanisms of insulin resistance in aging. J. Clin. Invest. 71, 1523–1535 (1983).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  119. López-Otín, C., Blasco, M.A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  120. Narici, M.V., Maganaris, C.N., Reeves, N.D. & Capodaglio, P. Effect of aging on human muscle architecture. J. Appl. Physiol. 95, 2229–2234 (2003).

    CAS  PubMed  Article  Google Scholar 

  121. Lamberts, S.W., van den Beld, A.W. & van der Lely, A.J. The endocrinology of aging. Science 278, 419–424 (1997).

    CAS  PubMed  Article  Google Scholar 

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Acknowledgements

We apologize to those investigators whose important work we were unable to cite or describe in depth, owing to the limited scope and space constraints of this Perspective. We are supported by the Howard Hughes Medical Institute, the Glenn Center for Research on Aging and the American Diabetes Association Pathway to Stop Diabetes (grant no. 1-15-INI-12 (CER)).

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Riera, C., Dillin, A. Can aging be 'drugged'?. Nat Med 21, 1400–1405 (2015). https://doi.org/10.1038/nm.4005

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