Pro-Aging Metabolic Reprogramming: A Unified Theory of Aging

Despite recent advances in understanding the biology of aging, the field remains fragmented due to the lack of a central organizing hypothesis. Although there are ongoing debates on whether the aging process is programmed or stochastic, it is now evident that neither perspective alone can fully explain the complexity of aging. Here, we propose the pro-aging metabolic reprogramming (PAMRP) theory, which integrates and unifies the genetic-program and stochastic hypotheses. This theory posits that aging is driven by degenerative metabolic reprogramming (MRP) over time, requiring the emergence of pro-aging substrates and triggers (PASs and PATs) to predispose cells to cellular and genetic reprogramming (CRP and GRP). (c) 2024 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).