Whether aging arises primarily from the progressive accumulation of molecular damage (error-based theories) or from regulated, development-related processes (programmatic theories) has been debated for more than a century. This question is central to aging research and shapes our conceptual understanding of aging. Although the existence of a dedicated aging program and the evolutionary advantage of aging remains controversial, the possibility that aging confers adaptive benefits at the species level should not be dismissed. Age-associated DNA methylation changes, which are enriched in developmental genes, support the hypothesis of an underlying program. However, the functional relevance of these epigenetic modifications remains unproven, and epigenetic clocks exhibit a substantial stochastic component – which is generally the case in epigenetics, also during development. This review argues that aging should not be interpreted exclusively as the result of random molecular damage or the output of a specific genetic program, but rather as a regulated modulation of how organisms acquire defects and epigenetic drift over time – possibly governed by feedback mechanisms of genetic and epigenetic networks – which may ultimately be beneficial to the species.
Wolfgang Wagner (Mon,) studied this question.