Preadipocyte secretory factors differentially modulate murine macrophage functions during aging which are reversed by the application of phytochemical EGCG

Emerging Dynamics of Macrophage Cellular Senescence and Immunosenescence in Governing Organismal Aging and Disease: Concepts and Opportunities

“…Nonetheless, in vitro studies have shown that on exposure to external stressors, macrophages can develop senescence like features including p21/p53 mediated cell cycle arrest (Nyunoya et al, 2003;Fong et al, 2007), altered morphology and the development of SA-β-gal activity (Kim et al, 2015). In a recent study, we observed that peritoneal macrophages isolated from old mice exhibit heterogenous and elongated morphology, enhanced expression of cell cycle inhibitors p53/p21 WAF1 /p16 Ink4a , and SAβ-gal activity as compared to macrophages isolated from younger animals (Kumar et al, 2020). In another study, age-related increase in the characteristic marker of senescence p16 Ink4a inhibited the normal phenotype of adipose tissue macrophages and contributed to type II diabetes risk (Fuentes et al, 2011).…”

“… Finally, nutraceuticals such as probiotics and polyphenols, as well as micronutrients are known to affect immunosenescence (Sharma et al, 2013;Wu et al, 2019), but whether the underlying mechanisms are relatable to cellular senescence is little understood (Sharma and Padwad, 2020) (Figure 3). In this regard, our previous work showed that green tea catechin EGCG can strongly attenuate the development of senescence-like features such as expression of p53/p21 WAF1 /p16 Ink4a , and SA-β-gal activity in macrophages exposed to conditioned media of senescent preadipocytes (Kumar et al, 2020). This suggests that nutraceuticals can impact senescence induction in macrophages, although further elaborative studies are warranted.…”

“…Thus, it is conceivable that dynamic interactions between specialized long-lived macrophages and host tissues with varying degree of cellular senescence, may differentially influence their functional capacity and/or the rate of cellular senescence (Figure 2). Although these aspects are less explored, our previous ex vivo study showed that the secretory phenotype of senescent preadipocytes, but not proliferating preadipocytes, could induce a senescence-like phenotype in peritoneal macrophages isolated from young animals (but not from old animals) characterized by a strong SA-β-gal activity, cellular hypertrophy, increase in p16 Ink4a expression and intracellular ROS production (Kumar et al, 2020). This implies that in a heterogenous and dynamic in vivo system, the highly senescence-prone adipose tissue (Minamino et al, 2009;Sharma et al, 2021) could directly influence cellular senescence in adipose tissue macrophages.…”

Obese Adipose Tissue Secretion Induces Inflammation in Preadipocytes: Role of Toll-Like Receptor-4

“…Recently, Kumar et al demonstrated that macrophages can be modulated in vitro, by using the CM of senescent or proliferative preadipocytes. While the treatment of proliferative preadipocytes with CM upregulated arginase-1 and mannose receptor genes toward an M2 phenotype, a suppression of these genes was observed when macrophages were cultured in the presence of secretory metabolites of senescent preadipocytes [ 47 ]. Preadipocytes from omental fat depots, which possess a high inflammatory profile, induce more monocyte/macrophage infiltration than those from subcutaneous AT [ 48 ].…”

Advancements in therapeutic drugs targeting of senescence

“… 93 In recent years, EGCG has attracted significant research interest due to its benefits in health effects. In a study by Kumar et al ., 94 EGCG treatment could alleviate macrophage inflammation and senescence, and curb incidences of inflammatory disorders in the elderly. Besides, catechins are powerful antioxidants and radical scavengers possessing a potential role in the management of neurodegenerative diseases and cardiovascular disorders.…”