Translating Basic Biology of Aging Into Treatments to Increase Human Healthspan

TL;DR

This paper discusses translating aging biology into treatments to improve human healthspan, focusing on mitochondrial proteostasis and using isotopes like D2O for translational research.

Contribution

The paper introduces a translational framework using stable isotope approaches, particularly D2O, to bridge basic aging biology with clinical applications.

Findings

Stable isotope methods like D2O are effective for measuring protein, DNA, and RNA synthesis in aging models.

Translational work in skeletal muscle helps address age-related sarcopenia through proteostatic mechanisms.

Reverse-translation strategies help refine mechanistic experiments based on clinical findings.

Abstract

The focus of the Miller lab is to translate basic biology of aging into treatments to increase human healthspan. We focus on proteostatic mechanisms in mitochondria to increase stress resistance for slowing aging. These studies concentrate primarily on skeletal muscle to minimize age-associated sarcopenia. We use stable isotope approaches that are amenable to both pre-clinical models and human subjects as a primary means to translate findings from the basic biology of aging to clinical implementation. Particularly useful has been the isotope D2O that we use to measure synthetic processes of protein, DNA, and RNA to answer basic and translational questions in relevant aging models including cells, yeast, C. elegans, rodents, canines, and humans. In this session, I will discuss how I sought training to allow me to perform translational work and the skillsets needed to be able to bridge pre-clinical to clinical work. I will also discuss how our clinical work informs our more mechanistic experiments as “reverse-translation”. Finally, I will present the challenges we have faced while performing work along the translational spectrum, and strategies we have used to successfully recruit and retain subjects in studies that require tissue sampling.