The relationships of animal age and caloric intake to cellular replicationin vivo and in vitro: A review

This brief review examines aging at the cellular level as expressed by cell replication rates ill vivo, clone size limits in vitro, and cell function in several tissues and organs. Studies are presented in which in vivo and i n vitro cell replication measurements were made for several cell types and organs in relation to animal age, diet, life span, and specific age-related pathologies. Among the events examined that affect cell replication and ce ll survival in vitro and in vitro over a lifetime are oxidative damage, tel omere shortening, and hormone and hormone receptor level changes. Long-term caloric restriction (CR) is favorable or protective for all of these event s when measured irt later life and comparisons are made to ad libitum (AL)- fed animals, and it is accompanied by more youthful rates of cell replicati on. It is proposed that the in vivo and in vitro measure of cellular replic ation constitute biomarkers of aging when applied to comparisons of CR and AL diet rodents, where they correlate with the delay of disease and extensi on of life span. Longitudinal studies are needed to confirm this. The occur rence of certain age-related pathophysiologic states, such as immune (T cel l) insufficiency, cataract, and senile osteopenia/osteoporosis, are accompa nied by major diminishments of replication rates, numbers, and functions of the essential cell types in the organs and tissues involved. However, dire ct evidence is lacking that diminished cell replication in specific organs contributes to the limitation of life span.