Aging is a complex process through which cumulative cellular wear and tear leaves us vulnerable to disease. One avenue for aging occurs when enzymes in our bodies break down food into energy. DMPI faculty member Dr. Matthew Hirschey aims to explain the biochemistry behind how metabolism contributes to aging and how the body defends itself.
Dr. Hirschey theorizes that the chemical reactions that break down food into energy could be wearing out metabolic enzymes. These enzymes repeatedly break chemical bonds to release stored energy and, in the process, collect acyl groups that are by-products of the reactions. Left unchecked, the aggregation of acyl groups hampers metabolic enzyme performance, leading to age-related disease. Dr Hirschey refers to this process as ‘carbon stress’. He proposes that healthy cells defend against carbon stress by deploying a class of enzymes called sirtuins to maintain metabolic homeostasis.
Two papers published by Dr. Hirschey’s team in the April edition of Cell Metabolism investigate understanding the mechanisms underlying carbon stress. Dr Hirschey’s overall conceptual framework relates the push and pull of nonenzymatic acyl addition and SIRT4 removal as a coordinated regulatory mechanism whose breakdown contributes to the decline in health associated with aging.