The relationships of animal age and caloric intake to cellular replication in vivo and in vitro: a review.

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This brief review examines aging at the cellular level as expressed by cell replication rates in vivo, clone size limits in vitro, and cell function in several tissues and organs. Studies are presented in which in vivo and in 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 cell survival in vitro and in vivo over a lifetime are oxidative damage, telomere shortening, and hormone and hormone receptor level changes. Long-term caloric restriction (CR) is favorable or protective for all of these events when measured in later life and comparisons are made to ad libitum (AL)-fed animals, and it is accompanied by more youthful rates of cell replication. It is proposed that in vivo and in vitro measures of cellular replication constitute biomarkers of aging when applied to comparisons of CR and AL diet rodents, where they correlate with the delay of disease and extension of life span. Longitudinal studies are needed to confirm this. The occurrence of certain age-related pathophysiologic states, such as immune (T cell) insufficiency, cataract, and senile osteopenia/osteoporosis, are accompanied by major diminishments of replication rates, numbers, and functions of the essential cell types in the organs and tissues involved. However, direct evidence is lacking that diminished cell replication in specific organs contributes to the limitation of life span.