The biological mechanisms of aging: A historical and critical overview

Abstract

This overview describes the historical background and modern versions of selected theories of the mechanisms of biological aging, including the mutation or genome instability theory, the free radical or oxidative stress theory, the mitochondrial theory, the error catastrophe theory, the altered protein or protein homeostasis dysregulation theory, the dysdifferentiation or epigenetic theory and the hyperfunction theory. The author has been involved in the development of some of these theories, which are therefore described in more detail. A discussion on the definition of aging and general comments on aging theory are included. The most popular theory of aging, the free radical or oxidative theory, was proposed more than 50 years ago but has recently faced severe criticism. To date, no single theory has been able to successfully explain the mechanisms of aging. We are thus awaiting the appearance of a new paradigm or an integration of the existing theories for a better understanding of the mechanisms of aging.