Metformin: Do we finally have an anti-aging drug?

Anisimov, Vladimir N.

doi:10.4161/cc.26928

Cited by 106 publications

(77 citation statements)

References 60 publications

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“…Despite several meta-analyses suggesting the contrary (that metformin does not lower cancer risk or mortality [18,19]), much effort is currently being devoted to in vitro and in vivo studies exploring potential mechanisms of action and biological effects of this drug on cancer prevention and treatment. Metformin is also increasingly being promoted as an anti-ageing drug [20]. How much substance is in this hype?…”

mentioning

confidence: 99%

60 years of metformin use: a glance at the past and a look to the future

Marshall

2017

Diabetologia

100

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mentioning

confidence: 99%

60 years of metformin use: a glance at the past and a look to the future

Marshall

2017

Diabetologia

100

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“…A juvenile cricket eats~30 mg of food/ day so the concentration of metformin in food that would deliver a high dose was 5.329×10 −5 g metformin/0.03 g food or 1.78×10 −3 g metformin/g diet. Anisimov (2013) reviewed dosages used in studies of metformin. The dose of metformin obtaining health and survival benefits in C57BL/6 mice was 0.1 % (w/w) in food (e.g., 1.0 × 10 −3 g/g) (Martin-Montalvo et al 2013)-very close to ours.…”

Section: Discussionmentioning

confidence: 99%

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

Hans

Lone

Aksenov

et al. 2015

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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 Beat 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.

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“…Comparison of effects of metformin on various biomarkers of aging in different strains of mice shows notable similarity in observed patterns. 34,35 It was demonstrated that the body weight and food consumption were unchanged or slightly decreased at some periods of life in metformin-treated rodents. The body temperature was similar in control and metformin-treated mice.…”

Section: Discussionmentioning

confidence: 99%

“…13 In a number of studies it was shown that administration of antidiabetic biguanides (phenformin, buformin and metformin) started at adult age increased life span and suppressed spontaneous and induced tumorigenesis. 2,[34][35][36][37][38] It is worthy to note that male and female adult 129/Sv mice demonstrated divergent reaction to the same dose of metformin. Metformin failed to increase life span of male F344 rats.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin

et al. 2014

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The perinatal (prenatal and early neonatal) period is a critical stage for hypothalamic programming of sexual differentiation as well as for the development of energy and metabolic homeostasis. We hypothesized that neonatal treatment with antidiabetic drug biguanide metformin would positively modify regulation of growth hormone -IGF-1 -insulin signaling pathway slowing down aging and improving cancer preventive patterns in rodents. To test this hypothesis male and female 129/Sv mice were s.c. injected with metformin (100 mg/kg) at the 3rd, 5th and 7th days after birth. Metformin-treated males consumed less food and water and their body weight was decreased as compared with control mice practically over their entire lifespan. There were no significant differences in age-related dynamics of food and water consumption in females and they were heavier than controls. The fraction of mice with regular estrous cycles decreased with age and demonstrated a tendency to decrease in the females neonatally treated with metformin. Neonatal exposure to metformin practically failed to change the extent of hormonal and metabolic parameters in blood serum of male and female mice. In males, neonatal metformin treatment significantly increased the mean life span (C20%, P < 0.05) and slightly increased the maximum life span (C3.5%). In females, the mean life span and median in metformin-treated groups were slightly decreased (¡9.1% and ¡13.8% respectively, P > 0.05) in comparison to controls, whereas mean life span of last 10% survivors and maximum life span were the same as in controls. Almost half (45%) of control male mice and 71.8% male mice neonatally exposed to metformin survived up to 800 d of age, the same age was achieved by 54.3% of mice in control female group and 30% of metformin-treated females (P < 0.03). Thus, neonatal metformin exposure slows down aging and prolongs lifespan in male but not in female mice.

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Metformin: Do we finally have an anti-aging drug?

Cited by 106 publications

References 60 publications

60 years of metformin use: a glance at the past and a look to the future

60 years of metformin use: a glance at the past and a look to the future

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

Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin

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