The Centriolar Damage Accumulation Theory of Aging (CDATA)

The Centriolar Damage Accumulation Theory of Aging (CDATA) proposes that the progressive, irreversible accumulation of oxidative post-translational modifications (PTMs) in the maternal centriole of adult tissue stem cells is the primary upstream cause of organismal aging. CDATA is built on five mechanistic postulates: the absolute structural non-renewability of the mother centriole’s core scaffold; the asymmetric retention ratchet that enforces preferential inheritance of the older, more damaged centriole by the self-renewing stem daughter — occurring in the context of a broader quality-control landscape in which the same daughter receives cytoplasmic renewal (new mitochondria, clean proteome) while retaining only the irremovable old centriole; five forms of irreversible PTM damage (carbonylation, hyperacetylation, aggregation, phosphorylation dysregulation, distal appendage loss); the dual functional integration of ciliogenesis and spindle assembly in a single structure; and a cell-autonomous ROS positive feedback loop. These postulates generate two primary failure tracks — Track A (ciliary loss → niche signaling collapse) and Track B (spindle fidelity loss → symmetric division catastrophe) — and four nested vicious cycles that account for the nonlinear acceleration of aging at tissue and organism levels. CDATA further incorporates the Irreversible Differentiation Inducer (IDI) hypothesis, proposing that two molecularly distinct sets of fate-determining molecules on the mother and daughter centrioles encode somatic and germline differentiation programs, with the daughter centriole’s set released specifically during granddaughter procentriole synthesis in the progenitor daughter cell. Together these mechanisms explain progressive regenerative rate decline, senescent tissue microenvironment formation, and the characteristic disease-like vicious cycles of late-life functional collapse. The theory generates six published and five new falsifiable experimental predictions. A companion computational model (Cell-DT) provides quantitative implementation.