Senotherapeutics in Aging and Age-Associated Disorders

Aging is a complex biological process marked by a gradual decline in physiological functions, which heightens susceptibility to diseases such as cancer, cardiovascular conditions, and neurodegenerative disorders. Cellular senescence plays a pivotal role in aging, wherein cells enter a state of irreversible cycle arrest, accumulating over time and contributing to age-related pathologies. Senescent cells (SnC) secrete pro-inflammatory factors through the senescence-associated secretory phenotype (SASP), promoting chronic inflammation and impairing tissue repair. In this chapter, we explore the hallmarks of cellular senescence and the potential of senotherapeutics, including senolytics, senomorphics, and immune-based therapies, to address age-related diseases. Senolytics, such as the combination of dasatinib and quercetin, selectively clear SnC, while senomorphics, like metformin or JAK inhibitors, modulate SASP effects to restore cellular function. Immune-based strategies, targeting markers like DPP4, enhance SnC removal. Preclinical studies suggest that these approaches may extend lifespan and slow disease progression. While promising, the long-term effects of these interventions require further evaluation, offering a potential pathway for improving aging outcomes and mitigating age-related diseases.