RIP kinases and necroptosis in aging and aging-related diseases

Aging is a natural process that is characterized by chronic, low-grade inflammation, which represents the primary risk factor in the pathogenesis of a variety of diseases, i.e. aging-related diseases. RIP kinases, in particular RIPK1 and RIPK3, have emerged as master regulators of proinflammatory responses that act either by causing apoptosis and necroptosis or by directly regulating intracellular inflammatory signaling. While, RIPK1/3 and necroptosis are intimately linked to multiple human diseases, the relationship among RIPK1/3, necroptosis, and aging remains unclear. In this review, we discuss current evidence arguing for the involvement of RIPK1/3 and necroptosis in the progression of aging. In addition, we provide updated information and knowledge on the role of RIPK1/3 and necroptosis in aging-related diseases. Leveraging these new mechanistic insights in aging, we postulate how our improved understanding of RIPK1/3 and necroptosis in aging may support the development of therapeutics targeting RIPK1/3 and necroptosis for the modulation of aging and treatment of aging-related diseases.