Molecular mechanisms of apoptosis in the cells of the immune system in human aging.

Aging is associated with progressive decline in immune functions and increased frequency of infections, autoimmunity, and cancer. Among immune functions, a decline in T-cell functions during aging predominates. In this review, I discuss the molecular signaling of three distinct pathways of apoptosis, namely the death receptor pathway, the mitochondrial pathway, and the most recently described endoplasmic reticulum stress pathway, and the relative sensitivity of naive, central memory, and effector memory CD8(+) T-cell subsets to apoptosis. In addition, I review apoptosis, especially via death receptor pathway, in naive and various memory subsets of CD4(+) and CD8(+) T cells (with primary emphasis on CD8(+) naive and memory subsets) in human aging and discuss the role of apoptosis in immune senescence.