Old Centrioles Make Old Bodies
Jaba Tkemaladze
Abstract
The paradox of organismal aging in the face of continuous cellular turnover remains a central question in biology. This article proposes a novel, integrative hypothesis: the non-renewed, asymmetrically inherited mother centriole in adult stem cells serves as a cumulative damage sensor and a primary driver of aging. I synthesize evidence to formulate the Centriolar Damage Accumulation Theory of Aging (CDATA). The theory posits that the biophysically stable mother centriole irreversibly accrues molecular damage (oxidative modifications, protein aggregates, loss of appendage proteins) over a lifetime. This "centriolar aging" impairs its core functions: templating the primary cilium (disrupting niche signaling) and organizing the mitotic spindle (compromising asymmetric cell division). Consequently, stem cell pools undergo exhaustion or dysfunctional expansion, leading to the failure of tissue homeostasis and the emergence of systemic aging phenotypes. I review supporting data from neural, hematopoietic, epithelial, and muscle stem cell niches, outline definitive experimental approaches for validation, discuss critiques and alternative viewpoints, and explore the profound therapeutic implications of targeting centriolar aging. This model reframes aging as a structural failure at the organelle level, offering a unified framework that connects subcellular wear to organismal decline.