Tirzepatide to Slow Biological Aging

Description

Primary Objective To estimate the potential effect of tirzepatide on biological aging using epigenetic age (based on established DNA methylation-based clocks), among people 55-70 years of age with an indication for tirzepatide weight loss therapy.

The principal investigator (PI) will measure DNA methylation-based aging clocks (DNAmAge, DNAm PhenoAge, DNAm GrimAge and DunedinPACE) before and after a 24-W course of tirzepatide. The primary analysis will determine whether tirzepatide treatment leads to a statistically significant change in biological age as indicated by these clocks. The PI will specifically assess epigenetic age acceleration (epigenetic age minus chronological age) and the pace of aging metric.

Secondary and Exploratory Objectives

Among people 55-70 years of age with an indication for tirzepatide weight loss therapy, the is aim to:

1. Estimate self-reported tolerability and acceptability of tirzepatide during the study period
2. Estimate changes in BMI and weight over 24 W of tirzepatide therapy, and in off-drug follow-up, between W 24 and 36
3. Estimate changes in physical function over 24 W of tirzepatide and, in off-drug follow-up, between W 24 and 36
4. Estimate changes in inflammatory, aging and neurocognitive biomarker profiles over 24 W of tirzepatide therapy, and in off-drug follow-up, between W 24 and 36
5. Estimate changes in other biological hallmarks/markers of aging
6. Explore relationships between the above outcomes