13. Aging Links Rising Damage Burden, Functional Decline, and Mortality Risk

In the simplest terms, the deleteriome rises → functions decline → disease and mortality risk increase (this is during adulthood; earlier, many functions improve while the deleteriome grows). Aging research can therefore treat function and mortality not as separate domains but as linked readouts of the same underlying accumulation of deleterious changes. However, the loss of function in turn promotes damage accumulation. Damage and dysfunction (e.g., dysregulation, hyperfunction, hypofunction) interact and can be viewed as components of the deleteriome and its responses; for example, overactivity can increase damage production and burden, and damage can trigger maladaptive responses. The key point is that aging is a systemic trajectory of rising burden that eventually overwhelms protective capacity; different mechanisms may contribute to and dominate at different ages and in different contexts (25–27).