by Frontiers Journals

Schematic illustration of the PAMRP theory of aging. Credit: Engineering (2024). DOI: 10.1016/j.eng.2024.09.010

Aging is a complex process that has long puzzled scientists. A recent study published in Engineering proposes a new theory called pro-aging metabolic reprogramming (PAMRP), which could change our understanding of aging.

The traditional debate on aging has centered around whether it is a programmed process or a result of stochastic events. The PAMRP theory combines these two perspectives. It suggests that aging is driven by degenerative metabolic reprogramming over time. This involves both the buildup of pro-aging substrates (PASs) through metabolic changes and the emergence of pro-aging triggers (PATs). The combination of PASs and PATs leads to metabolic reprogramming, which in turn causes cellular and genetic reprogramming, ultimately resulting in the aging process.

Metabolism plays a crucial role in the PAMRP theory. As organisms age, there are significant changes in metabolic pathways, such as shifts in energy production and nutrient utilization. These changes initially serve as an adaptive mechanism but can become maladaptive over time, contributing to aging. The theory also distinguishes between different types of metabolic reprogramming, such as adaptive and adverse, and between regenerative and degenerative processes.

The study provides several lines of evidence to support the PAMRP theory. For example, the conservation of basic metabolic pathways across species and the link between metabolism and aging-related factors like entropy and mitochondrial function. Caloric restriction, which is known to extend lifespan, is also seen as evidence as it regulates key controllers of cellular metabolism.

The PAMRP theory has potential implications for anti-aging interventions. It suggests that aging could be preventable, delayable and even reversible. Compounds that mimic the effects of caloric restriction, known as calorie restriction mimetics (CRMs), could be used to target the metabolic processes involved in aging. However, more research is needed to fully understand and validate the theory, including large-scale clinical trials to test the efficacy of anti-aging interventions in humans.

The PAMRP theory offers a new way of looking at the aging process and could pave the way for future research and interventions aimed at slowing or reversing aging. While the theory shows promise, further studies are required to confirm its validity and explore its full potential.

More information: Zhiguo Wang et al, Pro-Aging Metabolic Reprogramming: A Unified Theory of Aging, Engineering (2024). DOI: 10.1016/j.eng.2024.09.010

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