Richard A. Miller, MD, PhD (Director of the Glenn Center for Research on Aging and Professor of Pathology, University of Michigan)

Hosts: Drs. Maik Hüttemann and Tasnim Arroum

“Aging Rate Indicators and the Search for Anti-Aging Drugs”

Abstract

We now have at least 11 ways to slow aging and extend lifespan in mice: 5 single gene mutants, 2 or 3 diets, and at least 4 drugs. This toolkit allows us to ask if there are physiological or cellular traits that are shared among all varieties of slow-aging mice. The answer is “yes” – all slow-aging mice show changes in brown and white adipocytes, macrophage subsets, BDNF and DCX in brain, GPLD1 in liver and plasma, MEK1- and MEK3-regulated kinase pathways, mTORC1 activity, and cap-independent pathways of mRNA translation. These “Aging Rate Indicators,” unlike biomarkers of age, can discriminate control from slow-aging mice even in early adulthood, and thus lend themselves to rapid, relatively inexpensive screening of newly proposed candidate anti-aging drugs. They also provide clues for selection of novel targets for anti-aging drugs. In parallel, new machine learning methods applied to plasma metabolomic data provide a possible bridge to the investigation of putative anti-aging drugs in humans.