What is the mechanism by which metformin (biguanide) reverses aging?

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From the Research

Metformin does not definitively reverse aging, but it may slow certain aging processes through multiple mechanisms, primarily by improving healthspan and reducing the risk of age-related diseases, as suggested by the most recent and highest quality study 1. The drug activates AMP-activated protein kinase (AMPK), which improves cellular energy metabolism and reduces inflammation. Metformin decreases insulin levels and improves insulin sensitivity, potentially mimicking some benefits of caloric restriction—a well-established intervention that extends lifespan in various species. It also reduces oxidative stress by decreasing the production of reactive oxygen species in mitochondria and may inhibit the mTOR pathway, which regulates cell growth and is linked to longevity. Some of the key benefits of metformin include:

  • Reducing the risk of cardiometabolic disorders, neurodegeneration, chronic inflammation, and frailty, as shown in studies 2, 3, 4, 5
  • Potentially repurposing metformin for chemoprevention or adjuvant therapy for certain types of cancer
  • Inducing autophagy by activation of AMPK, which can promote healthspan by hormesis-like mechanisms
  • Positively influencing the gut microbiome and protecting against age-related diseases like cancer, cardiovascular disease, and neurodegenerative conditions While typically prescribed for diabetes at doses of 500-2000mg daily, metformin is being investigated in clinical trials like TAME (Targeting Aging with Metformin) to evaluate its potential anti-aging effects in non-diabetic individuals. However, it's essential to understand that metformin is not approved as an anti-aging treatment, and its long-term use for this purpose should only be considered under medical supervision due to potential side effects like gastrointestinal issues and, rarely, lactic acidosis.

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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