Mitochondrial dysfunction as the “mother” of all hallmarks of aging
Volkmar Weissig
Abstract
The idea of mitochondria being linked to biological aging goes back to the 1950s, when Denham Harman proposed his free radical theory of aging which eventually became the “Mitochondrial Free Radical Theory of Aging” (MFRTA). After the turn of the century, data were published that weakened Harman’s MFRTA causing doubt about the validity of the oxidative stress theory of aging. However, later mitochondrial dysfunction was acknowledged as being one of the “Hallmarks of Aging” followed most recently by considerations about a central role malfunctioning mitochondria may play for the biological process of aging. This review focuses on mitochondrial dysfunction contributing to all aspects of aging by a variety of mechanisms which go far beyond the lack of ATP and increased oxidative stress as caused by malfunctioning mitochondria.