Molecular and Biological Factors in Aging

Age is the major risk factor for morbidity, the most prevalent diseases, and mortality in the modern world. Therefore, mechanisms determining life span and the link between life span and disease are of the greatest interest in biomedical science, and the search for such mechanisms has given rise to numerous perspectives and theories. Thus, evolutionary concepts such as “antagonistic pleiotropy,” which posit that mechanisms driving biological aging (or more usefully, senescence) are likely to be highly variable depending on species and individuals, have been widely accepted. However, in this chapter we suggest that a variety of phenomena suggest that general mechanisms are indeed responsible for senescence and the link between life span and age-related diseases. Among these phenomena are the observations that average life span is genetically determined across species, and that dietary restriction and genetic inhibition of the insulin-like signaling pathway increase life span and delay age-dependent diseases across a wide range of species. These observations are consistent with other studies that reducing body temperature similarly increases life span across a wide variety of species. These studies led to the rate-of-living theory, which proposed that metabolic processes drive aging. The present review describes possible common molecular mechanisms linking dietary restriction and IGF-1 signaling to life span and age-related diseases.