Cellular senescence and apoptosis: how cellular responses might influence aging phenotypes

Aging in complex multi-cellular organisms such as mammals entails distinctive changes in cells and molecules that ultimately compromise the fitness of adult organisms. These cellular and molecular changes lead to the phenotypes we recognize as aging. This review discusses some of the cellular and molecular changes that occur with age, specifically changes that occur as a result of cellular responses that evolved to ameliorate the inevitable damage that is caused by endogenous and environmental insults. Because the force of natural selection declines with age, it is likely that these processes were never optimized during their evolution to benefit old organisms. That is, some age-related changes may be the result of gene activities that were selected for their beneficial effects in young organisms, but the same gene activities may have unselected, deleterious effects in old organisms, a phenomenon termed antagonistic pleiotropy. Two cellular processes, apoptosis and cellular senescence, may be examples of antagonistic pleiotropy. Both processes are essential for the viability and fitness of young organisms, but may contribute to aging phenotypes, including certain age-related diseases. (C) 2002 Elsevier Science Inc. All rights reserved.