Cellular senescence: Implications for metabolic disease

- Aging and obesity are drivers of cellular senescence.
- Senescent biomarkers accumulate in metabolic tissues, such as liver, muscle, and fat.
- The SASP and mitochondrial dysfunction contribute to metabolic impairments.
- Therapies that alter senescent burden or the SASP may improve metabolic health.

The growing burden of obesity- and aging-related diseases has hastened the search for governing biological processes. Cellular senescence is a stress-induced state of stable growth arrest strongly associated with aging that is aberrantly activated by obesity. The transition of a cell to a senescent state is demarcated by an array of phenotypic markers, and leveraging their context-dependent presentation is essential for determining the influence of senescent cells on tissue pathogenesis. Biomarkers of senescent cells have been identified in tissues that contribute to metabolic disease, including fat, liver, skeletal muscle, pancreata, and cardiovascular tissue, suggesting that pharmacological and behavioral interventions that alter their abundance and/or behavior may be a novel therapeutic strategy. However, contradictory findings with regard to a protective versus deleterious role of senescent cells in certain contexts emphasize the need for additional studies to uncover the complex interplay that defines multi-organ disease processes associated with obesity and aging.