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, 3 (2), 148-57

If Started Early in Life, Metformin Treatment Increases Life Span and Postpones Tumors in Female SHR Mice

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If Started Early in Life, Metformin Treatment Increases Life Span and Postpones Tumors in Female SHR Mice

Vladimir N Anisimov et al. Aging (Albany NY).

Abstract

Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer in mice, although its effects vary, depending on mice strain and gender. Here we showed that chronic treatment of female outbred SHR mice with metformin started at the age of 3, 9 or 15 months decreased body temperature and postponed age-related switch-off of estrous function. Surprisingly, metformin did not affect levels of serum cholesterol, triglycerides, glucose and insulin. Treatment with metformin started at the age of 3 months increased mean life span by 14% and maximum life span by 1 month. The treatment started at the age of 9 months insignificantly increased mean life span by only 6%, whereas the treatment started at the age of 15 months failed to increase life span. The mean life span of tumor-free mice was increased by 21% in 'the youngest group', by 7% in 'middle-aged group' and in contrast was reduced by 13% in 'the oldest group'. When started at the age of 3 and 9 months, metformin delayed the first tumor detection by 22% and 25%, correspondingly. Thus, in female SHR mice, metformin increased life span and postponed tumors when started at the young and middle but not at the old age. In contrast, metformin improves reproductive function when started at any age.

Conflict of interest statement

The authors of this manuscript have no conflict of interests to declare.

Figures

Figure 1.
Figure 1.
Age-related dynamics of body weight (A), food consumption (B), body temperature (C) and of the incidence of mice with irregular estrous cycles (D) in SHR mice not treated and treated with metformin starting at the age of 3, 9 or 15 months. The difference with the controls is significant, p<0.05: а- metformin 3 m; b - metformin 9 m; c - metformin 15 m)
Figure 2.
Figure 2.
Survival curves and tumor yield curves in female in SHR mice not treated and treated with metformin starting at the age of 3 (A, B), 9 (C, D) or 15 months (E, F).

Comment in

  • Gerosuppressant metformin: less is more.
    Menendez JA, Cufí S, Oliveras-Ferraros C, Vellon L, Joven J, Vazquez-Martin A. Menendez JA, et al. Aging (Albany NY). 2011 Apr;3(4):348-62. doi: 10.18632/aging.100316. Aging (Albany NY). 2011. PMID: 21483040 Free PMC article. No abstract available.

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