, 37:31 | Cite as

Impacts of metformin and aspirin on life history features and longevity of crickets: trade-offs versus cost-free life extension?

  • Harvir Hans
  • Asad Lone
  • Vadim Aksenov
  • C. David Rollo


We examined the impacts of aspirin and metformin on the life history of the cricket Acheta domesticus (growth rate, maturation time, mature body size, survivorship, and maximal longevity). Both drugs significantly increased survivorship and maximal life span. Maximal longevity was 136 days for controls, 188 days (138 % of controls) for metformin, and 194 days (143 % of controls) for aspirin. Metformin and aspirin in combination extended longevity to a lesser degree (163 days, 120 % of controls). Increases in general survivorship were even more pronounced, with low-dose aspirin yielding mean longevity 234 % of controls (i.e., health span). Metformin strongly reduced growth rates of both genders (<60 % of controls), whereas aspirin only slightly reduced the growth rate of females and slightly increased that of males. Both drugs delayed maturation age relative to controls, but metformin had a much greater impact (>140 % of controls) than aspirin (~118 % of controls). Crickets maturing on low aspirin showed no evidence of a trade-off between maturation mass and life extension. Remarkably, by 100 days of age, aspirin-treated females were significantly larger than controls (largely reflecting egg complement). Unlike the reigning dietary restriction paradigm, low aspirin conformed to a paradigm of “eat more, live longer.” In contrast, metformin-treated females were only ~67 % of the mass of controls. Our results suggest that hormetic agents like metformin may derive significant trade-offs with life extension, whereas health and longevity benefits may be obtained with less cost by agents like aspirin that regulate geroprotective pathways.


Metformin Aspirin Acheta domesticus Life extension Growth Trade-offs 



No agency supported this study.

Conflict of interest

The authors declare no conflicts of interest.


  1. Aksenov V, Long J, Liu J, Szechtman H, Khanna P, Matravadia S, Rollo CD (2013) A complex dietary supplement augments spatial learning, brain mass, and mitochondrial electron transport chain activity in aging mice. AGE 35:23–33PubMedCentralPubMedGoogle Scholar
  2. Al-Gohary OM, Al-Kassas RS (2000) Stability studies of aspirin-magaldrate double layer tablets. Pharm Acta Helv 74:351–360PubMedGoogle Scholar
  3. Algra AM, Rothwell PM (2012) Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials. Lancet Oncol 13:518–527PubMedGoogle Scholar
  4. Anisimov VN (2013) Metformin: do we finally have an anti-aging drug? Cell Cycle 12:3483–3489PubMedCentralPubMedGoogle Scholar
  5. Anisimov VN, Egormin PA, Bershtein LM, Zabezhinskii MA, Piskunova TS, Popovich IG, Semenchenko AV (2005a) Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice. Bull Exp Biol Med 139:721–723PubMedGoogle Scholar
  6. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, Re F (2005b) Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/neu transgenic mice. Exp Gerontol 40:685–693PubMedGoogle Scholar
  7. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Yurova MV, Kovalenko IG, Poroshina TE, Semenchenko AV (2008) Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 7:2769–2773PubMedGoogle Scholar
  8. Anisimov VN, Egormin PA, Piskunova TS, Popovich IG, Tyndyk ML, Yurova MN, Zabezhinski MA, Anikin IV, Karkach AS, Romanyukha AA (2010) Metformin extends life span of HER-2/neu transgenic mice and in combination with melatonin inhibits growth of transplantable tumors in vivo. Cell Cycle 9:188–197PubMedGoogle Scholar
  9. Anisimov VN, Berstein LM, Popovich IG, Zabezhinski MA, Egormin PA, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Kovalenko IG, Poroshina TE (2011) If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging 3:148–157PubMedCentralPubMedGoogle Scholar
  10. Arkadieva AV, Mamonov AA, Popovich IG, Anisimov VN, Mikhelson VM, Spivak IM (2011) Metformin slows down ageing processes at the cellular level in SHR mice. Cell Tissue Biol 5:151–159Google Scholar
  11. Ayyadevara S, Bharill P, Dandapat A, Hu C, Khaidakov M, Mitra S, Shmookler Reis RJ, Mehta JL (2013) Aspirin inhibits oxidant stress, reduces age-associated functional declines, and extends lifespan of Caenorhabditis elegans. Antioxid Redox Signal 18:481–490PubMedGoogle Scholar
  12. Barneoud P, Curet O (1999) Beneficial effects of lysine acetylsalicylate, a soluble salt of aspirin, on motor performance in a transgenic model of amyotrophic lateral sclerosis. Exp Neurol 155:243–251PubMedGoogle Scholar
  13. Bartke A, Sun LY, Longo V (2013) Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev 93:571–598PubMedCentralPubMedGoogle Scholar
  14. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high calorie diet. Nature 444:337–342PubMedGoogle Scholar
  15. Bonnefont-Rousselot D, Raji B, Walrand S, Gardes-Albert M, Jore D, Legrand A, Vasson M (2003) An intracellular modulation of free radical production could contribute to the beneficial effects of metformin towards oxidative stress. Metab Clin Exp 52:586–589PubMedGoogle Scholar
  16. Braendle C, Heyland A, Flatt T (2011) Integrating mechanistic and evolutionary analysis of life history variation. In: Flatt T, Heyland A (eds) Mechanisms of life history evolution: the genetics and physiology of life history traits and trade-offs. Oxford University Press, Oxford, pp 3–10Google Scholar
  17. Burkewitz K, Zhang Y, Mair WB (2014) AMPK at the nexus of energetics and aging. Cell Metab 20:10–25Google Scholar
  18. Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J (2009) AMPK regulates energy expenditure by modulating NAD1 metabolism and SIRT1 activity. Nature 458:1056–1060PubMedCentralPubMedGoogle Scholar
  19. Chen H, Maklakov AA (2012) Longer life span evolves under high rates of condition-dependent mortality. Curr Biol 22:2140–2143PubMedGoogle Scholar
  20. Choi KM, Lee HL, Kwon YY, Kang MS, Lee SK, Lee CK (2013) Enhancement of mitochondrial function correlates with the extension of lifespan by caloric restriction and caloric restriction mimetics in yeast. Biochem Biophys Res Commun 441:236–242PubMedGoogle Scholar
  21. Constantini D, Metcalfe NB, Monaghan P (2010) Ecological processes in a hormetic framework. Ecol Lett 13:1435–1447Google Scholar
  22. 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 5:3557. doi: 10.1038/ncomms4557 PubMedCentralPubMedGoogle Scholar
  23. Cutler RG (1984a) Antioxidants, aging and longevity. In: Pryor WA (ed) Free radicals in biology, vol VI. Academic, New York, pp 371–428Google Scholar
  24. Cutler RG (1984b) Evolutionary biology of aging and longevity in mammalian species. In: Johnson JE (ed) Aging and cell function. Plenum, New York, pp 1–147Google Scholar
  25. Dabour N, Bando T, Nakamura T, Miyawaki K, Mito T, Ohuchi H, Ohuchi H, Noji S (2011) Cricket body size is altered by systemic RNAi against insulin signaling components and epidermal growth factor receptor. Develop Growth Differ 53:857–869Google Scholar
  26. Din FV, Valanciute A, Houde VP, Zibrova D, Green KA, Sakamoto K, Alessi DR, Dunlop MG (2012) Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology 142:1504–1515PubMedCentralPubMedGoogle Scholar
  27. Duffy PH, Lewis SM, Mayhugh MA, Trotter RW, Latendresse JR, Thorn BT, Feuers RJ (2004) The effects of different levels of dietary restriction on neoplastic pathology in the male Sprague-Dawley rat. Aging 16:448–456Google Scholar
  28. Edward DA, Chapman T (2011) Mechanisms underlying reproductive trade-offs: costs of reproduction. In: Flatt T, Heyland A (eds) Mechanisms of life history evolution: the genetics and physiology of life history traits and tradeoffs. Oxford University Press, Oxford, pp 137–152Google Scholar
  29. El Mir MY, Noguera V, Fontaine E, Avéret N, Rigoulet M, Leverve X (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J Biol Chem 275:223–228PubMedGoogle Scholar
  30. Flatt T (2011) Survival costs of reproduction in Drosophila. Exp Gerontol 46:369–375PubMedGoogle Scholar
  31. Galluzzi L, Kepp O, Vander Heiden MG, Kroemer G (2013) Metabolic targets for cancer therapy. Nat Rev 12:829–846Google Scholar
  32. Grandison RC, Piper MDW, Partridge L (2009) Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462:1061–1065PubMedCentralPubMedGoogle Scholar
  33. Grosser N, Schroder H (2003) Aspirin protected bovine endothelial cells from oxidant damage via the nitric oxide-cGMP pathway. Arterioscler Thromb Vasc Biol 23:1345–1351PubMedGoogle Scholar
  34. Gupta V, Liu S, Ando H, Ishii R, Tateno S, Kaneko Y, Yugami M, Sakamoto S, Yamaguchi Y, Nureki O, Handa H (2013) Salicylic acid induces mitochondrial injury by inhibiting ferrochelatase heme biosynthesis activity. Mol Pharmacol 84:824–833PubMedGoogle Scholar
  35. Hack MA (1997) The effects of mass and age on standard metabolic rate in house crickets. Physiol Entomol 22:325–331Google Scholar
  36. Hardie DG (2005) New roles for the LKB1-AMPK pathway. Curr Opin Cell Biol 17:167–173PubMedGoogle Scholar
  37. Hardie DG, Ross FA, Hawley SA (2012) AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 13:251–262PubMedGoogle Scholar
  38. Hawley SA, Fullerton MD, Ross FA, Schertzer JD, Chevtzoff C, Walker KJ, Peggie MW, Zibrova D, Green KA, Mustard KJ, Kemp BE, Sakamoto K, Steinberg GR, Hardie DG (2012) The ancient drug salicylate directly activates AMP activated protein kinase. Science 336:918–922PubMedCentralPubMedGoogle Scholar
  39. Hochschild R (1971) Effect of membrane stabilizing drugs on mortality in Drosophila melanogaster. Exp Gerontol 6:133–151PubMedGoogle Scholar
  40. Holliday R (1989) Food, reproduction and longevity: is the extended lifespan of calorie restricted animals an evolutionary adaptation? Bioessays 10:125–127PubMedGoogle Scholar
  41. Hou M, Venier N, Sugar L, Musquera M, Pollak M, Kiss A, Fleshner N, Klotz L, Venkateswaran V (2010a) Protective effect of metformin in CD1 mice placed on a high carbohydrate-high fat diet. Biochem Biophys Res Commun 397:537–542PubMedGoogle Scholar
  42. Hou X, Song J, Li XN, Zhang L, Wang X, Chen L, Shen YH (2010b) Metformin reduces intracellular reactive oxygen species levels by upregulating expression of the antioxidant thioredoxin via the AMPK-FOXO3 pathway. Biochem Biophys Res Commun 396:199–205PubMedGoogle Scholar
  43. Ingram DK, Zhu M, Mamczarz J, Zou S, Lane MA, Roth GS, deCabo R (2006) Calorie restriction mimetics: an emerging research field. Aging Cell 5:97–108PubMedGoogle Scholar
  44. Jafari M (2010) Drosophila melanogaster as a model system for the evaluation of anti-aging compounds. Fly 4:253–257PubMedGoogle Scholar
  45. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493:338–345PubMedCentralPubMedGoogle Scholar
  46. Kengeri SS, Maras AH, Suckow CL, Chiang EC, Waters DJ (2013) Exceptional longevity in female Rottweiler dogs is not encumbered by investment in reproduction. AGE 35:2503–2513PubMedCentralPubMedGoogle Scholar
  47. King EG, Roff DA, Fairbairn DJ (2011) Trade-off acquisition and allocation in Gryllus firmus: a test of the Y model. J Evol Biol 24:256–264PubMedGoogle Scholar
  48. Kirkwood TBL (2008) A systematic look at an old problem. Nature 451:644–647PubMedGoogle Scholar
  49. Koornneef A, Leon-Reyes A, Ritsema T, Verhage A, Den Otter FC, Van Loon LC, Pieterse CMJ (2008) Kinetics of salicylate-mediated suppression of jasmonate signaling reveal a role for redox modulation. Plant Physiol 147:1358–1368PubMedCentralPubMedGoogle Scholar
  50. Leroi AM (2001) Molecular signals versus the Loi de Balancement. Trends Ecol Evol 16:24–29PubMedGoogle Scholar
  51. Long J, Aksenov V, Rollo CD, Liu J (2012) A complex dietary supplement modulates nitrative stress in normal mice and in a new mouse model of nitrative stress and cognitive aging. Mech Aging Dev 133:523–529PubMedGoogle Scholar
  52. Lopez-Martınez G, Hahn DA (2014) Early life hormetic treatments decrease irradiation-induced oxidative damage, increase longevity, and enhance sexual performance during old age in the Caribbean fruit fly. PLoS ONE 9(1):e88128. doi: 10.1371/journal.pone.0088128 PubMedCentralPubMedGoogle Scholar
  53. Lyn J, Aksenov V, LeBlanc Z, Rollo CD (2012) Life history features and aging rates: insights from intra-specific patterns in the cricket Acheta domesticus. Evol Biol 39:371–387Google Scholar
  54. Lyn J, Naik W, Aksenov V, Rollo CD (2011) Development of the cricket Acheta domesticus as a model of aging. AGE 33:509–522PubMedCentralPubMedGoogle Scholar
  55. Ma TC, Buescher JL, Oatis B, Funk JA, Nash AJ, Carrier RL, Hoyt KR (2007) Metformin therapy in a transgenic mouse model of Huntington’s disease. Neurosci Lett 411:98–103PubMedGoogle Scholar
  56. Martin-Montalvo M, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, Schwab M, Pollak M, Zhang Y, Yu Y, Becker KG, Bohr VA, Ingram DK, Sinclair DA, Wolf NS, Spindler SR, Bernier M, de Cabo R (2013) Metformin improves healthspan and lifespan in mice. Nat Commun 4:2192. doi: 10.1038/ncomms3192 PubMedCentralPubMedGoogle Scholar
  57. Massie HR, Williams TR, Iodice AA (1985) Influence of anti-inflammatory agents on the survival of Drosophila. J Gerontol 40:257–260PubMedGoogle Scholar
  58. McCarty MF (2014) AMPK activation-protean potential for boosting healthspan. AGE 36:641–663PubMedCentralPubMedGoogle Scholar
  59. Nieman DC, Trone GY, Austin MD (2003) A new handheld device for measuring resting metabolic rate and oxygen consumption. J Am Diet Assoc 103:588–593PubMedGoogle Scholar
  60. Onken B, Driscoll M (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS One 5(1):e8758. doi: 10.1371/journal.pone.0008758 PubMedCentralPubMedGoogle Scholar
  61. Owen MR, Doran E, Halestrap AP (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Biochem J 348:607–614PubMedCentralPubMedGoogle Scholar
  62. Phillips T, Leeuwenburgh C (2004) Lifelong aspirin supplementation as a means to extending life span. Rejuvenation Res 7:243–251PubMedGoogle Scholar
  63. Pugh TD, Klopp RG, Weindruch R (1999) Controlling caloric consumption: protocols for rodents and rhesus monkeys. Neurobiol Aging 20:157–165PubMedGoogle Scholar
  64. Rivas-San Vicente M, Plasencia J (2011) Salicylic acid beyond defence: its role in plant growth and development. J Expt Bot 62:3321–3338Google Scholar
  65. Rizzo MR, Mari D, Barbieri M, Ragno E, Grella R, Provenzano R, Villa I, Esposito K, Giugliano D, Paolisso G (2005) Resting metabolic rate and respiratory quotient in human longevity. J Clin Endocrinol Metab 90:409–413PubMedGoogle Scholar
  66. Rocha JS, Bonkowski MS, Masternak MM, França LR, Bartke A (2012) Effects of adult onset mild calorie restriction on weight of reproductive organs, plasma parameters and gene expression in male mice. Anim Reprod 9:40–51PubMedCentralPubMedGoogle Scholar
  67. Rollo CD (1986) A test of the principle of allocation using two sympatric species of cockroaches. Ecology 67:616–628Google Scholar
  68. Rollo CD (1994) Phenotypes: their epigenetics, ecology and evolution. Chapman and Hall, LondonGoogle Scholar
  69. Rollo CD (2010) Aging and the mammalian regulatory triumvirate. Aging Dis 1:105–138PubMedCentralPubMedGoogle Scholar
  70. Rollo CD (2012) Circadian redox regulation. In: Pantopoulos K, Schipper HM (eds) Principles of free radical biomedicine. Nova Science, New York, pp 575–627Google Scholar
  71. Rollo CD (2014) Trojan genes and transparent genomes: sexual selection, regulatory evolution and the real hopeful monsters. Evol Biol 41:367–387Google Scholar
  72. Rollo CD, Hawryluk MD (1988) Compensatory scope and resource allocation in two species of aquatic snails. Ecology 69:146–156Google Scholar
  73. Rollo CD, Carlson J, Sawada M (1996) Accelerated aging of giant transgenic mice is associated with elevated free radical processes. Can J Zool 74:606–620Google Scholar
  74. Rollo CD, Kajiura LJ, Wylie B, D’Souza S (1999) The growth hormone axis, feeding, and central allocative regulation: lessons from giant transgenic growth hormone mice. Can J Zool 77:1861–1873Google Scholar
  75. Rothwell PM, Fowkes FGR, Belch JF, Ogawa H, Warlow CP, Meade TW (2011) Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377:31–41PubMedGoogle Scholar
  76. Rothwell PM, Price JF, Fowkes FGR, Zanchetti A, Roncaglioni MC, Tognoni G, Lee R, Belch JFF, Wilson M, Mehta Z, Meade TW (2012) Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials. Lancet 379:1602–1612PubMedGoogle Scholar
  77. Ruffer M, Steipe B, Zenk MH (1995) Evidence against specific binding of salicylic acid to plant catalase. FEBS Lett 377:175–180PubMedGoogle Scholar
  78. Saul N, Pietsch K, Stürzenbaum SR, Menzel R, Steinberg CEW (2013) Hormesis and longevity with tannins: free of charge or cost-intensive? Chemosphere 93:1005–1008PubMedGoogle Scholar
  79. Sharma VK, Nautiyal V, Goel KK, Sharma A (2010) Assessment of thermal stability of metformin hydrochloride. Asian J Chem 22:3561–3566Google Scholar
  80. Shimamura H, Terada Y, Okado T, Tanaka H, Inoshita S, Sasaki S (2003) The PI3-kinase-Akt pathway promotes mesangial cell survival and inhibits apoptosis in vitro via NF-κB and Bad. J Am Soc Nephrol 14:1427–1434PubMedGoogle Scholar
  81. Simon AF, Shih C, Mack A, Benzer S (2003) Steroid control of longevity in Drosophila melanogaster. Science 299:1407–1410PubMedGoogle Scholar
  82. Slack C, Foley A, Partridge L (2012) Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS ONE 7:e47699. doi: 10.1371/journal.pone.0047699 PubMedCentralPubMedGoogle Scholar
  83. Smith DL Jr, Elam CF Jr, Mattison JA, Lane MA, Roth GS, Ingram DK, Allison DB (2010) Metformin supplementation and life span in Fischer-344 rats. J Gerontol Ser A Biol Sci Med Sci 65:468–474Google Scholar
  84. Snavely MJ, Price JC, Jun HW (1993) The stability of aspirin in a moisture containing direct compression tablet formulation. Drug Dev Ind Pharm 19:729–738Google Scholar
  85. Spindler SR (2010) Caloric restriction: from soup to nuts. Ageing Res Rev 9:324–353PubMedGoogle Scholar
  86. Spindler SR, Mote PL, Li R, Dhahbi JM, Yamakawa A, Flegal JM, Jeske DR, Li R, Lublin AL (2013a) β1-Adrenergic receptor blockade extends the life span of Drosophila and long-lived mice. AGE 35:2099–2109PubMedCentralPubMedGoogle Scholar
  87. Spindler SR, Mote PL, Flegal JM, Teter B (2013b) Influence on longevity of blueberry, cinnamon, green and black tea, pomegranate, sesame, curcumin, morin, pycnogenol, quercetin, and taxifolin fed iso-calorically to long-lived, F1 hybrid mice. Rejuvenation Res 16:143–151PubMedGoogle Scholar
  88. Strong R, Miller RA, Astle CM, Floyd RA, Flurkey K, Hensley KL, Javors MA, Leeuwenburgh C, Nelson JF, Ongini E, Nadon NL, Warner HR, Harrison DE (2008) Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice. Aging Cell 7:641–650PubMedCentralPubMedGoogle Scholar
  89. Thalera JS, McArta SH, Kaplanc I (2012) Compensatory mechanisms for ameliorating the fundamental trade-off between predator avoidance and foraging. PNAS 109:12075–12080Google Scholar
  90. Torres MA, Jones JDG, Dang JL (2006) Reactive oxygen species signaling in response to pathogens. Plant Physiol 141:373–378PubMedCentralPubMedGoogle Scholar
  91. van Noordwijk A, de Jong G (1986) Acquisition and allocation of resources: their influence on variation in life history tactics. Am Nat 128:137–142Google Scholar
  92. Verhage A, van Wees SCM, Pieterse CMJ (2010) Plant immunity: it’s the hormones talking, but what do they say? Plant Physiol 154:536–540PubMedCentralPubMedGoogle Scholar
  93. Viollet B, Guigas B, Garcia NS, Leclerc J, Foretz M, Andreelli F (2012) Cellular and molecular mechanisms of metformin: an overview. Clin Sci 122:253–270PubMedCentralPubMedGoogle Scholar
  94. Walker DW, McColl G, Jenkins NL, Harris J, Lithgow GJ (2000) Evolution of lifespan in C. elegans. Nature 405:296–297PubMedGoogle Scholar
  95. Wan QL, Zheng SQ, Wu GS, Luo HR (2013) Aspirin extends the lifespan of Caenorhabditis elegans via AMPK and DAF-16/FOXO in dietary restriction pathway. Exp Gerontol 48:499–506PubMedGoogle Scholar
  96. Wang J, Gallagher D, DeVito LM, Cancino GI, Tsui D, He L, Keller GM, Frankland PW, Kaplan DR, Miller FD (2012) Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 11:23–35PubMedGoogle Scholar
  97. Wit J, Sarup P, Lupsa N, Malte H, Frydenberg J, Loeschcke V (2013) Longevity for free? Increased reproduction with limited trade-offs in Drosophila melanogaster selected for increased life span. Exp Gerontol 48:349–357PubMedGoogle Scholar
  98. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686–689PubMedGoogle Scholar
  99. Wu R, Lamontagne D, de Champlain J (2002) Antioxidative properties of acetylsalicylic acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation 105:387–392PubMedGoogle Scholar
  100. Xie Z, Chen Z (1999) Salicylic acid induces rapid inhibition of mitochondrial electron transport and oxidative phosphorylation in tobacco cells. Plant Physiol 120:217–225PubMedCentralPubMedGoogle Scholar
  101. Yan S, Dong X (2014) Perception of the plant immune signal salicylic acid. Curr Opin Plant Biol 20:64–68PubMedGoogle Scholar
  102. Yang Y, Qi M, Mei C (2004) Endogenous salicylic acid protects rice plants from oxidative damage caused by aging as well as biotic and abiotic stress. Plant J 40:909–919PubMedGoogle Scholar
  103. Zakikhani M, Blouin M, Piura E, Pollak MN (2010) Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Can Res Treat 123:271–279Google Scholar
  104. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108:1167–1174PubMedCentralPubMedGoogle Scholar

Copyright information

© American Aging Association 2015

Authors and Affiliations

  • Harvir Hans
    • 1
  • Asad Lone
    • 1
  • Vadim Aksenov
    • 1
  • C. David Rollo
    • 1
  1. 1.Department of BiologyMcMaster UniversityHamiltonCanada

Personalised recommendations