Biological aging is a multifaceted process that resists reduction to a single mechanistic explanation. In the review titled ‘Simply aging,’ published in the Proceedings of the National Academy of Sciences, the author, Vadim Gladyshev, presents a conceptual framework aimed at simplifying the discussion surrounding aging biology.
The article posits that aging is a default outcome of living organisms. The central theme is the concept of the ‘deleteriome,’ which refers to the accumulation of harmful changes that occur as biological processes operate imperfectly over time. These changes progressively diminish the functional reserve of organisms, leading to age-related decline.
Gladyshev argues that the deleteriome serves as a unifying framework for understanding various aspects of aging, including molecular damage, regulatory drift, maladaptive remodeling, and system-level failures. This perspective challenges the notion that aging can be solely attributed to specific genes, pathways, or hallmarks, suggesting instead that evolution has shaped maintenance and renewal systems that inherently possess limitations and trade-offs.
Interestingly, the review highlights that aging begins during development, following an initial phase of rejuvenation in early embryonic stages. This insight suggests that the aging process is not merely a consequence of later life but is rooted in earlier biological events.
Modern advancements in biomarkers have made it increasingly possible to measure biological age, albeit imperfectly. The review emphasizes that biological age varies across different cells, organs, and systems, and can be influenced by environmental factors and interventions. While some contexts may allow for partial reversibility or resetting of biological age, the review underscores that aging itself remains an irreversible process.
Ultimately, this model seeks to connect foundational principles of aging with practical implications for measurement, intervention, and strategies aimed at extending longevity. The author suggests that significant gains in lifespan may be achievable, both within the constraints of existing species and potentially beyond.