Death of lymphocytes: A clue to immune deficiency in human aging

Extract: There is only one way to conceive; however, there are multiple ways to die. The latter is particularly true with each and every cell in our body. One of the ways to die is by programmed cell death or apoptosis (a suicidal form of cell death), which is a natural form of cell death. Apoptosis is critical in embryogenesis, metamorphosis, cellular homeostasis, and removal of unwanted and mutated cells. In the immune system, apoptosis plays an important role in the development of thymocytes (immature T lymphocytes in the thymus), selection of T cell repertoire, deletion of self-reactive lymphocytes, cytotoxicity towards target cells by natural killer and cytotoxic T lymphocytes, and termination of effector lymphocytes at the end of an immune response. Apoptosis is tightly regulated by a set of genes, which either promote or inhibit apoptosis. There are several signaling pathways that mediate apoptosis, namely the death receptor (extrinsic) pathway, mitochondrial (intrinsic) pathway, and the endoplasmic reticulum (ER) pathway. Common to these pathways is the recruitment of adaptor proteins to form a scaffold complex that activates initiator caspases (cysteine proteases), which in-turn activate effector caspases. These effector caspases act as a molecular chainsaw and cleave a large number of cytoplasmic and nuclear substrates, resulting in the morphological and biochemical changes characteristic of apoptosis.