This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) provides $828,960 to Cedars-Sinai Medical Center to examine the role of biological aging mechanisms in Alzheimer's disease (AD) pathology and whether modulating these processes with metformin can improve indicators of AD risk. The study will leverage an ongoing randomized clinical trial of metformin versus placebo for frailty prevention in older adults without dementia. Key objectives include evaluating the association between hallmarks of aging (e.g., cellular senescence, inflammation, metabolism) and AD biomarkers, assessing longitudinal trajectories in aging pathways and their relationship to cognition and AD markers, and examining if metformin can alter these AD-related indicators. This project aims to enhance understanding of the link between biological aging and AD risk, as well as provide proof-of-concept data on targeting aging processes as a novel approach for AD prevention.