Graduation Year

2023

Document Type

Open Access Senior Thesis

Degree Name

Bachelor of Arts

Department

Biology

Reader 1

Elise Ferree

Reader 2

Aditi Vyas

Abstract

Aging is a non-adaptive epiphenomenon that characterizes the terminal phase of life. Aging leads to the dysregulation of metabolic processes that subsequently drive the downregulation of critical nutrient sensing pathways and autophagy, while increasing inflammation, cellular senescence, stem cell depletion, reactive oxygen species, and DNA damage; the gestalt of which is the aging phenotype. Age-induced subcellular alterations impact the whole organism, from cosmetic factors, such as grey hair and wrinkles, to the development of cardiovascular diseases, cancer, and neurodegenerative diseases. Fortunately, humans may have discovered a means of delaying aging through treatment with metformin. Metformin is an FDA-approved drug that has been a safe, inexpensive, and effective type 2 diabetes treatment for over 60 years. Research in model organisms has revealed metformin’s capacity to extend both healthspan and lifespan, decrease the incidence of diseases of aging, and modulate aging-regulating metabolic pathways. In type 2 diabetics, metformin has successfully attenuated diseases of aging, decreasing the incidence of cancer and cardiovascular disease. Metformin also shows promise for the treatment and prevention of neurodegenerative diseases. Currently, two major trials (TAME and MILES) are underway to ascertain if the healthspan and lifespan-extending benefits of metformin can be generalized to the non-diabetic population. The present thesis sets forth a comprehensive review of metformin’s capacity to attenuate aging and proposes a study synergistic with TAME and MILES to determine the optimal age of initiation to produce the greatest benefits from metformin treatment in the general population. Metformin demonstrates the potential to act as both a treatment and prophylactic to mitigate the progression of aging, leading to greater time spent in good health, and ultimately, a longer life.

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