Metformin improves putative longevity effectors in peripheral mononuclear cells from subjects with prediabetes. A...

Area of Science:

• Gerontology
• Metabolic Health
• Pharmacology

Background:

• Prediabetes elevates cardiovascular risk and mortality.
• Metformin exhibits anti-ageing properties in preclinical studies.
• Identifying interventions to mitigate prediabetes complications is crucial.

Purpose of the Study:

• To investigate metformin's effect on longevity pathways in prediabetic subjects.
• To assess metformin's impact on metabolic parameters and insulin sensitivity.
• To explore metformin's influence on molecular markers of aging.

Main Methods:

• A randomized, single-blind, placebo-controlled trial involving 38 prediabetic subjects.
• Metformin (1500 mg/day) or placebo administered for 2 months.
• Analysis of anthropometric, metabolic, gene/protein expression (SIRT1, mTOR, p53, p66Shc), enzyme activity, telomere length, and plasma N-glycans.

Main Results:

• Metformin significantly improved metabolic parameters and insulin sensitivity.
• Increased SIRT1 expression and promoter accessibility, elevated mTOR gene expression, and reduced p70S6K phosphorylation observed.
• Favorable modifications in plasma N-glycan profiles were noted with metformin treatment.

Conclusions:

• Metformin ameliorated key longevity pathways in prediabetic individuals.
• The findings suggest metformin may counteract aging processes associated with prediabetes.
• Clinical trial identifier: NCT01765946.