Anisimov Vladimir N, Berstein Lev M, Popovich Irina G, Zabezhinski Mark A, Egormin Peter A, Piskunova Tatiana S, Semenchenko Anna V, Tyndyk Margarita L, Yurova Maria N, Kovalenko Irina G, Poroshina Tatiana E
N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg, Russia.
Aging (Albany NY). 2011 Feb;3(2):148-57. doi: 10.18632/aging.100273.
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.
高血糖和高胰岛素血症会加速衰老和癌症进程。抗糖尿病双胍类药物（如二甲双胍）可降低血糖、胰岛素和IGF-1水平。二甲双胍能延长小鼠寿命并预防癌症，不过其效果因小鼠品系和性别而异。我们在此表明，对3、9或15月龄的雌性远交SHR小鼠进行二甲双胍长期治疗，可降低体温，并推迟与年龄相关的发情功能停止。令人惊讶的是，二甲双胍并未影响血清胆固醇、甘油三酯、血糖和胰岛素水平。3月龄开始用二甲双胍治疗可使平均寿命延长14%，最大寿命延长1个月。9月龄开始治疗仅使平均寿命显著增加6%，而15月龄开始治疗则未能延长寿命。在“最年轻组”，无肿瘤小鼠的平均寿命增加了21%，“中年组”增加了7%，相比之下，“最年长组”则减少了13%。3月龄和9月龄开始使用二甲双胍时，首次检测到肿瘤的时间分别相应推迟了22%和25%。因此，在雌性SHR小鼠中，二甲双胍在年轻时和中年时开始使用可延长寿命并推迟肿瘤发生，但老年时开始使用则无效。相比之下，二甲双胍在任何年龄开始使用均可改善生殖功能。
