%0 Journal Article
%T Health benefits of late-onset metformin treatment every other week in mice
%A Alessandra Warren
%A Christopher Hine
%A Darisbeth Rosario Lugo
%A David G. Le Couteur
%A Hector Mora
%A Ignacio Navas-Enamorado
%A Irene Alfaras
%A James R. Mitchell
%A Michel Bernier
%A Rafael de Cabo
%A Sarah J. Mitchell
%A Vickie Hoffmann
%A Victoria C. Cogger
%J Archive of "NPJ Aging and Mechanisms of Disease".
%D 2017
%R 10.1038/s41514-017-0018-7
%X Characteristics of mice on intermittent metformin treatment. a Protocol design. Male mice (108 week-old) were fed a standard diet (SD) without (nˋ=ˋ68) or with 1% metformin in the diet every-other week (EOW, nˋ=ˋ64) or for two consecutive weeks each month (2WM, nˋ=ˋ67) for 24 weeks. At the indicated time points (weeks), body composition (NMR), metabolic assessment (RER), and physical performance tests (PPT) were performed on non-fasted animals, whereas blood glucose and lactate levels were measured in 6-h fasted mice. Sac, sacrifice of a subset of animals for tissue collection and analysis (SD, nˋ=ˋ10; EOW, nˋ=ˋ6; 2WM, nˋ=ˋ6). b Kaplan每Meier survival curve for the three experimental groups of mice (SD, EOW, 2WM). No extension of maximal lifespan was observed. c Body weight profile over the lifespan. Data include all live animals at each time point. Inset, Body weight at the initiation (0) and after 10 weeks of treatment (10) (SD, nˋ=ˋ68(0) and 64(10); EOW, nˋ=ˋ64(0) and 58(10); 2WM, nˋ=ˋ67(0) and 57(10)). #pˋ<ˋ0.05 compared to tˋ=ˋ0; *pˋ<ˋ0.05 compared to SD at tˋ=ˋ10 weeks. d Body temperature. e Food consumption. f Average daily food consumption per mouse. g The data shown in panel f was segregated by whether mice were on metformin treatment or returned to SD without metformin. h Correlations between % body fat (upper panel) or lean-to-fat ratio (lower panel) and time of death (nˋ=ˋ12 in each group) (upper, Fˋ=ˋ22.27; dFn, dFd (1, 35); Pˋ<ˋ0.0001); lower, (Fˋ=ˋ11.1; dFn, dFd (1, 35); Pˋ<ˋ0.002). i每j Mice were subjected to metabolic assessment after 17 weeks of treatment (SD, nˋ=ˋ11; EOW on metformin, nˋ=ˋ6; EOW off metformin, nˋ=ˋ6; 2WM on metformin, nˋ=ˋ9; 2WM off metformin, nˋ=ˋ3): i Respiratory exchange ratio (RER) values over the course of 48ˋh; j RER values shown in panel i were segregated based on the light and dark periods of the L12:D12 cycle; k Latency to fall from wire hang was measured after 16 weeks of treatment (SD, nˋ=ˋ47; EOW on metformin, nˋ=ˋ12; EOW off metformin, nˋ=ˋ7; 2WM on metformin, nˋ=ˋ0; 2WM off metformin, nˋ=ˋ22) before (upper panel) and after (lower panel) correction for body weight. l, m At 13每16 weeks of treatment, mice were fasted for 6ˋh (SD, nˋ=ˋ8每10; EOW, nˋ=ˋ9每10; 2WM, nˋ=ˋ9每10) and circulating levels of l glucose and m lactate were measured. n每r The following analyses were carried out at 17 weeks of treatment in fed mice (SD, nˋ=ˋ10; EOW, nˋ=ˋ6; 2WM, nˋ=ˋ6): n blood glucose; o serum insulin levels; p HOMA-IR index; q blood lactate; r Serum levels of leptin. s Correlation between circulating levels of leptin and amount
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696465/