Cellular senescence in lymphoid organs and immunosenescence

Abstract

Immunosenescence is a multi-faceted phenomenon at the root of age-associated immune dysfunction. It can lead to an array of pathological conditions, including but not limited to a decreased capability to surveil and clear senescent cells (SnCs) and cancerous cells, an increased autoimmune response leading to tissue damage, a reduced ability to tackle pathogens, and a decreased competence to illicit a robust response to vaccination. Cellular senescence is a phenomenon by which oncogene-activated, stressed or damaged cells undergo a stable cell cycle arrest. Failure to efficiently clear SnCs results in their accumulation in an organism as it ages. SnCs actively secrete a myriad of molecules, collectively called senescence-associated secretory phenotype (SASP), which are factors that cause dysfunction in the neighboring tissue. Though both cellular senescence and immunosenescence have been studied extensively and implicated in various pathologies, their relationship has not been greatly explored. In the wake of an ongoing pandemic (COVID-19) that disproportionately affects the elderly, immunosenescence as a function of age has become a topic of great importance. The goal of this review is to explore the role of cellular senescence in age-associated lymphoid organ dysfunction and immunosenescence, and provide a framework to explore therapies to rejuvenate the aged immune system.

Adulthood systemic inflammation accelerates the trajectory of age-related cognitive decline

“…Finally, it is possible that behavioral and brain differences were due to the history of systemic inflammation interacting with the age-related increase in chronic low level systemic inflammation, sometimes referred to as “inflammaging”. A bout of severe systemic inflammation can induce senescence of peripheral cells, including cells of the immune system [ 65 – 69 ]. In turn, senescent cells exhibit a senescence associated secretory phenotype (SASP), releasing toxic factors: pro-inflammatory cytokines, chemokines, extracellular matrix proteases, and microRNA in extracellular vesicles, that contribute to age-related diseases.…”

Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review

“…In conclusion, cellular senescence-mediated understanding of aging and age-dependent disorders is rapidly gaining attention as a viable therapeutic target (Soto-Gamez and Demaria, 2017 ). It is increasingly being realized that cellular senescence could be central to developing anti-aging strategies as evidence of its integration with other established age-related phenomena such as immunosenescence and gut dysbiosis is also emerging (Budamagunta et al, 2021 ; Sharma, 2022 ). Besides, the striking presence of cellular senescence in pathophysiologically distinct human disorders renews hope of a single targetable approach to disease management during aging.…”

Glucose Metabolism and Aging of Hematopoietic Stem and Progenitor Cells

“…Anti-apoptotic proteins such as BCL2, BCL-XL, and BCL-W are upregulated and seem to be essential for the survival of senescent HSPC in animal models [ 24 , 25 , 76 ]. This has inspired the development of inhibitors of anti-apoptotic factors as “senolytic” agents to eliminate senescent cells [ 25 , 68 , 76 , 77 ]. Inhibitors of anti-apoptotic factors, e.g., ABT263 and ABT737, are able to selectively deplete senescent HSPC and clearance of the latter has led to rejuvenation not only of HSPC, but also to improved cardiovascular function, reduced osteoporosis and extended health span in naturally aging mice [ 76 , 78 ].…”