Senescence and life span

Abstract

Senescence is a general cellular process that occurs as a response to stress and damage. It forms an alternative response of cells to damage that might otherwise cause programmed cell death. Whereas telomere shortening leading to telomere dysfunction was the first described cause of senescence, it is now known that senescence can result from many sources of damage. Senescent cells are found in tissues in vivo, but the cause of senescence in these cells is mostly unknown. In many cases, senescence may be the result of the action of activated oncogenes in cells. By preventing activated oncogenes from initiating a clone of neoplastic cells, senescence acts as a protective mechanism against cancer development. Until recently, the fate of senescent cells in vivo was unknown, but new evidence indicates that they are cleared by components of the innate immune system. In this way, senescence and apoptosis act as parallel pathways by which severely damaged cells are eliminated from the body. Some senescent cells persist in tissues, in some cases increasing in frequency as a function of age. It is hypothesized that these persistent senescent cells have adverse effects on tissue function. If so, senescence may be an example of antagonistic pleiotropy, providing an anticancer mechanism in early life but having adverse effects on tissue function in late life. Much more research is needed to address the broader question of the overall impact of senescence on life span.

Apoptosis and aging: increased resistance to apoptosis enhances the aging process

“…Hinkal et al [47] observed that hyperactive p53 ?/m mice exhibited increased numbers of SA-b-gal-positive cells in all tissues studied, i.e., kidney, liver, and spleen, particularly with old age. Recent reviews have discussed in detail the role of cellular senescence in organismal aging [1,2,23,48].…”

“…Cells also display prominent age-related structural and functional changes, e.g., dysfunction in mitochondrial respiration, disturbances in proteasomal and autophagic degradation, and accumulation of waste material into the cytoplasm and the lysosomal compartment. Cellular senescence is the state where cells have irreversibly lost their proliferation ability, and they exhibit deficiencies in maintaining their homeostatic processes [1,2]. The number of senescent cells increases in tissues with aging ( Fig.…”

The specific role of pRb in p16INK4A-mediated arrest of normal and malignant human breast cells

“…[3][4][5] This growth arrest is often mediated through RB family proteins (pRb, p107 and p130), which have similar structures and overlapping functions. 6,7 RB family proteins are regulated by cyclin-dependent kinases (CDKs) 2, 4 and 6.…”

Glutamine metabolism in advanced age

“…140 Senescence and apoptosis act as parallel pathways by which severely damaged cells are eliminated from the body by the innate immune system. 141 Programmed cell death pathways are promising targets for interventions in aging and aging-related diseases. But to inhibit them, muscle atrophy that occurs with aging must be prevented.…”