Metformin in Longevity Study (MILES Clinical Trial)

Introduction and Specific Aims: Metformin, an FDA approved first-line drug for the treatment of type 2 diabetes, has known beneficial effects on glucose metabolism. Evidence from animal models and in vitro studies suggest that in addition to its effects on glucose metabolism, metformin may influence metabolic and cellular processes associated with the development of age-related conditions, such as inflammation, oxidative damage, diminished autophagy, cell senescence and apoptosis. As such, metformin is of particular interest in clinical translational research in aging since it may influence fundamental aging factors that underlie multiple age-related conditions. We therefore propose a pilot study to examine the effect of metformin treatment on the biology of aging in humans. Namely, whether treatment with metformin will restore the gene expression profile of older adults with impaired glucose tolerance (IGT) to that of young healthy subjects.

Specific Aims: We propose a 6-week randomized, double blind, placebo controlled crossover pilot study of metformin treatment in older adults (age > 60, n=15), with the following aims:

Specific Aim 1: To determine if treatment with metformin (2000 mg/day) will restore the gene expression profile of older, glucose intolerant adults to that of young healthy subjects. Specific Aim 2: To assess the relationship between changes in gene expression with selected phenotypic variables, including changes in glucose tolerance, vascular function, oxidative stress and inflammation.

Trial design:

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Column names key for Muscle and Adipose TPM matrices:

Msl.1.2.Placebo = Muscle sample for Subject 1 who received Placebo treatment at Visit 2 of the crossover trial WF.10.1.Metformin = Whole Fat (subcutaneous adipose) sample for Subject 2 who received Metformin treatment at visit 1 of the crossover trial