The Biology of Aging

In humans, aging is inexorable. The progressive decrease in physiological capacity and the reduced ability to respond to environmental stresses lead to increased susceptibility and vulnerability to disease. Consequently, mortality due to all causes increases exponentially with aging. Attempts at understanding the causes of aging are limited by the complexity of the problem. Aging changes are manifest from the molecular to the organismic level; environmental factors affect experimental observations; secondary effects complicate elucidation of primary mechanisms; and precisely defined, easily measurable biomarkers are lacking. No one unifying theory may exist, since the mechanisms of aging could be quite distinct in different organisms, tissues, and cells. Evolutionary pressures have selected for successful reproduction, making it likely that the post-reproductive physiology of an organism (i.e., aging) is an epigenetic and pleiotropic manifestation of the optimization for early fitness. Indeed, antagonistic pleiotropy, wherein genes that enhance early survival and function but are disadvantageous later in life, may play an overriding role in aging. Theories of aging can be divided into two general categories: stochastic and developmental-genetic. These are not mutually exclusive, particularly when considering the free radical/mitochondrial DNA theory of aging. Increasing evidence suggests that cellular senescence and organismic aging are antagonistically pleiotropic manifestations of evolutionary pressures to prevent malignant transformation. In other words, aging may be the price we pay to avoid cancer. The beneficial paradox may be that the maximum lifespan potential of humans may have been achieved, in part, due to our ability to grow old.