Senescence violates the most basic tenet of natural selection by causing death rather than individual survival. Thus, current theories favor the concept of antagonistic pleiotropy (AP) to explain how aging emerged in metazoans. Presumably, pleiotropic genes reduce vigor and limit longevity in adults. However, they also promote fitness and reproduction in juveniles, causing them to be selected and retained in the gene pool. The general hypothesis presented herein is a special case of AP that identifies the common cause and mechanism of aging in iteroparous (i.e., capable of reproducing multiple times) animals. It ascribes senescence to unremitting, nonprogrammed change or remodeling forced upon the adult soma by postmaturation expression of developmental gene(s) affecting dynamic transformation of the single-celled conceptus into a complex, multicellular organism. Whereas persistent somatic change is necessary for development to proceed normally, it also has the potential to erode homeostasis in adults after maturation is complete. Thus, developmental inertia is the primary cause of senescence, whereas decay of internal order and integrated function among interdependent systems of the body is the general mechanism by which aging progresses over time. Accordingly, this global pathogenic process creates an environment in which the many recognized, age-associated physiologic and metabolic sequelae can arise as consequences of senescence rather than causes of it. Paradoxically, the genes that promote somatic remodeling essential for development and survival also guarantee aging and death by the same action whose outcomes differ only by the time it is expressed relevant to maturation.

There is consensus among biogerontologists that aging occurs either as the result of a purposeful genome-based, evolved program or due to spontaneous, randomly occurring, maladaptive events. Neither concept has yet identified a specific mechanism to explain aging’s emergence and acceleration during mid-life and beyond. Presented herein is a novel, unifying mechanism with empirical evidence that describes how aging becomes continuous with development. It assumes that aging emerges from deterioration of a regulatory process that directs morphogenesis and morphostasis. The regulatory system consists of a genome-wide “backbone” within which its specific genes are differentially expressed by the local epigenetic landscapes of cells and tissues within which they reside, thereby explaining its holistic nature. Morphostasis evolved in humans to ensure the nurturing of dependent offspring during the first decade of young adulthood when peak parental vitality prevails in the absence of aging. The strict redundancy of each morphostasis regulatory cycle requires sensitive dependence upon initial conditions to avoid initiating deterministic chaos behavior. However, when natural selection declines as midlife approaches, persistent, progressive, and specific DNA damage and misrepair changes the initial conditions of the regulatory process, thereby compromising morphostasis regulatory redundancy, instigating chaos, initiating senescence, and accelerating aging thereafter.

Based upon evolvability theory, phenotypes like aging that offer no apparent individual benefit may evolve nonetheless. Pursuant to that concept, the evolution of a hypothetical, genome-based aging pr