Carnosine Stimulates Macrophage-Mediated Clearance of Senescent Skin Cells Through Activation of the AKT2 Signaling Pathway by CD36 and RAGE

Abstract

Background: Macrophages can selectively recognize and eliminate senescent cells, but this function is impaired with age, resulting in excessive accumulation of senescent cells in the skin, which ultimately causes skin aging. Therefore, enhancing the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts from aging skin may be an effective skin rejuvenation strategy.Methods: In this study, a macrophage and senescent skin cell co-culture model was established whereby THP-1-derived macrophages and tert-butyl hydroxide-induced senescent skin cells (HaCaT and HFF-1) were grown in the same culture. Senescent skin cells were detected by the SPiDER-βgal assay, and the expression of secretory phenotype factors related to senescence was assayed by qPCR. The effect of carnosine on the number of SA-β-gal positive skin cells in the macrophage-senescent skin cell co-culture was evaluated and compared with that in the senescent skin cell monoculture.Results: Carnosine promoted macrophage-mediated elimination of senescent skin cells in the co-culture. Through the AKT2 signaling pathway, carnosine upregulated the expression of CD36 and receptors for advanced glycation end products and elevated the phagocytic capacity of the macrophages, thereby promoting the ability of the macrophages to eliminate the senescent skin cells.Conclusions: Carnosine could boost the immune surveillance ability of macrophages to clear senescent keratinocytes and fibroblasts in the macrophage-senescent skin cell co-culture by activating the AKT2 signaling pathway, suggesting the possibility of using carnosine as an agent to reverse skin aging.

Balenine, Imidazole Dipeptide Promotes Skeletal Muscle Regeneration by Regulating Phagocytosis Properties of Immune Cells

“…In this study, we demonstrated that the phagocytic activity of RAW264.7 cells was increased by balenine treatment. Consistent with our results, it was reported that carnosine, an imidazole peptide, could enhance the phagocytic activity of macrophages through an activation of the AKT2 signaling pathway by CD36, a membrane protein that facilitates fatty acid uptake, and RAGE, a receptor for advanced glycation end products, to eliminate senescent skin cells [ 19 ]. However, further studies are required to identify the mechanism of phagocytosis activity by balenine treatment.…”

“…It was recently reported that the treatment of carnosine can promote the phagocytic capacity of macrophages to eliminate senescent skin cells [ 19 ]. Given the importance of phagocytic modulation by active compounds such as peptides, balenine may also regulate immune responses to clear degenerated organs.…”

Immunomodulatory Effects of Chicken Broth and Histidine Dipeptides on the Cyclophosphamide-Induced Immunosuppression Mouse Model

“…During the last 5 years, the ability of CAR to modulate different activities of immune cells such as macrophages has been demonstrated [ 16 , 17 ]. It has been demonstrated that the interaction of CAR with particular receptors on the cell membrane could modify macrophage function by enhancing their phagocytotic activity [ 18 , 19 ]. It has also been demonstrated that HD can influence NO production and macrophage polarization [ 20 , 21 ].…”

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

“…The immune homeostasis function of macrophages is impaired with age, resulting in the decline of its selective scavenging ability to aging cells. This will contribute to the abnormal accumulation of senescent cells in skin [ 166 ]. However, there is little research on how UV-induced senescent cells bypass immune clearance.…”