Changing Aging — 8

In contrast with young, healthy cells, senescent cells have multiple distinguishing features, including larger size, increased size and number of mitochondria and lysosomes, inability to divide that leads to growth arrest, shortened telomeres, and richness in the enzyme beta-galactosidase (and change to a secretory phenotype). Old cells are not necessarily categorized as senescent—there is a biological shift that occurs in some of them that leads to their properties. And senescent cell features vary considerably, so they shouldn’t be thought of as a simple categorization. Their accumulation promotes chronic inflammation, which in turn, as a stressor, induces more cells to become senescent. These cells function as bad actors beyond the aging process, linked to cardiovascular, brain, kidney, liver, musculoskeletal, and endocrine diseases. Senescence of immune cells leads to decreased function, less antibody production, and increased susceptibility to infections. A strong case for the senescence of neurons as a driver for brain aging has been made. But all senescent cells aren’t bad. There is considerable tissue and cell specificity, whereby some types of senescent cells promote healthy functions such as wound healing, tumor suppression, pancreatic beta cell insulin secretion, and tissue repair. Nonetheless, nonselective elimination of senescent cells promotes lifespan in mice, and in the antiaging clinical trials section to follow I’ll address the many drug “senolytic” efforts that target old cells.

Exhausted Stem Cells

Adult stem cells vary by tissue, such as blood (hematopoietic, HSCs) or muscle satellite cells (MuSCs). Wherever they are, they are pivotal to health, owing to their self-renewal capability. Stem cells are endowed with long life, making them particularly vulnerable to cell damage that occurs with aging. One of the ways this is manifest in older adults is sarcopenia—loss of muscle mass and strength—since MuSC function is impaired, with less ability to repair or regenerate skeletal muscle cells, and chronic activation of pro-inflammatory pathways leading to exhaustion. MuSCs can, in part, be rejuvenated with exercise. Similarly, for blood stem cells, aging results in reduced fitness and function, and an antibody that depletes exhausted HSCs in mice rejuvenates the immune system. These examples provide strong support that stem cells are not only a part or bystander of the aging process but also a driver.