Multiple pathology and tails of disability: Space-time structure of disability in longevity

Disability and the resulting lowered quality of life are serious issues accompanying increased longevity. Curiously, despite its potential contribution to aging theory, complete statistical and etiological structures of this common and unwelcome aging phenotype before death have not been well identified. Another neglected issue in aging and disability is the principles of phylogenesis and morphogenesis, which contemporary life science invariably starts with. In the present review these two related subjects are addressed, with an introduction of an analysis on patients and published data. Statistically rigorous log–normal and normal distributions distinguish disability for its duration and age-wise distribution, respectively. Multiple pathology and diverse effects of various endogenous diseases on disability are confirmed. The robust long-tailed log–normal distribution for various phases of disability validates the fact that patients in disability undergo series of stochastic subprocesses of many independent endogenous diseases until death. For 60% of patients, the log–normal distribution is mimicked by a random walk model. Diseases of core organs are major causes of the long tails. A declining force of natural selection after reproduction and trade-off of life history through pleiotropy of the genes are considered to be the roots of aging. The attenuated selection pressure and the resulting decrease of genetic constraints produce an increased opportunity for chance and stochastics. Elucidated stochastic behaviors of disability underscore the key role of chance in aging. Evolutionary modifications in the development of the structure tend to favor developmentally later stages first. Distal parts are developmentally last, therefore most subject to modification. The rate of molecular evolution of the genes is also found to be relatively slow at the core and rapid at the edge of cells and organs. Therefore, systems at the core must be relatively slow and inactive to comply with pleiotropy and trade-offs in comparison with systems at the edge. Hence, against flat and probabilistic aging, the core organs must be moulded to be more robust with a lower threshold for dysfunction, to age relatively slowly, and should have less of a disease quota in aging. The principle of core protective aging assures possibilities not only to reduce disability but also to accomplish the Third Age as well. Finally, it must also be acknowledged that the principle is a double-edged sword. Paradoxically, the developed biological and societal organization provides protection for the injured core, and so develops long tails of disability. The principle of core protective aging re-emphasizes the key role of prevention in order to reduce the amount of disability.