Highlights From the Latest in Diabetes Research
Cellular Senescence and Aging: Implications for Both Duration and Quality of Life
A new report provides intriguing new data on the potential role of cellular senescence in aging and metabolic dysfunction. Aging is accompanied by development of chronic diseases as well as loss of function, changes in body composition, and insulin resistance. Despite these well-recognized patterns, the specific mechanisms by which aging increases risk of disease and loss of function are poorly understood. Cellular senescence, which results in accumulation of senescent cells in various tissues, is postulated to contribute to aging in humans and other organisms through unfavorable effects on tissue structure and function. If causally associated with aging-related dysfunction, cellular senescence could be a meaningful target for future therapies. Recently, Baker et al. published data from an intriguing set of experiments in progeroid mice in which a novel transgene (INK-ATTAC) was used to induce removal of p16Ink4a-positive senescent cells from various tissues.
Baker’s experiments yielded a number of interesting results among treated mice, including clearance of senescent cells from several tissues that often show age-related dysfunction, including adipose tissue, skeletal muscle, and eye. These experiments also suggested that ongoing removal of senescent cells delayed the onset of aging-related phenotypes such as cataracts and sarcopenia and late-life clearance inhibited progression of established pathologies. Treated mice also performed better on treadmill testing and lost less body fat, a recognized aging phenomenon in mice. Notably, other age-related changes including abnormalities in cardiac structure and function, which may occur independently of p16Ink4a, were similar in treated and untreated animals.
The data from these experiments provide a tantalizing glimpse into the potential therapeutic implications associated with targeting the mechanisms underpinning cellular senescence and perhaps its associated metabolic dysfunction. However, it should be emphasized that these experiments were conducted in a mouse model of accelerated aging in which accumulation of senescent cells is …