Anti-skin aging effects of aerobic and resistance exercise via IL-18/IL-18R pathway in SAMP8 mice
AIM:To investigate the effects of aerobic and anti-resistance exercise on skin aging in SAMP8 mice via interleukin-18(IL-18)/IL-18 receptor(IL-18R)pathway and provide new concepts for anti-skin aging and pre-vention and treatment of chronic inflammatory skin-related diseases.METHODS:Twenty-four healthy male 28-week-old rapidly aging SAMP8 mice were randomly divided into model group,aerobic exercise group,and resistance exercise group,with 8 mice in each group.Eight same-aged rapidly aging SAMR1 mice were used as control group.The mice in aerobic exercise group underwent running table training at a constant speed(1 time per day,5 times per week)for 8 weeks,and those in model group underwent incremental weight-bearing ladder training for 8 weeks(1 time every other day,3 times per week).The HE staining was performed to observe the structural changes of the epidermis and dermis,and Weigert staining was conducted to observe the changes in skin elastic fibers.Immunohistochemistry was performed to observe the expression of skin aging markers P16 and P21.The ELISA was used to detect the concentrations of serum and skin inflammatory factors IL-18,IL-1β and tumor necrosis factor-α(TNF-α)and the levels of dermal IL-18R and IL-18 binding protein(IL-18BP).Double immunofluorescence staining of IL-18 and IL-18R was conducted.The RT-qPCR was used to detect the mRNA expression levels of IL-18 and IL-18R.RESULTS:Compared with control group,the mice in model group exhibited obvious signs of aging.The results of HE staining revealed indications such as rough skin texture and skin thinning.Weigert staining revealed the following:the elastic fibers were disordered,separated,thickened,shortened,twisted,and broken.The expression levels of P16 and P21 proteins in the epidermis and dermis were elevated(P<0.01).Serum and skin IL-1β,TNF-α and IL-18 levels were significantly higher.Skin IL-18R content was significant-ly higher,and IL-18BP content was significantly lower(P<0.05 or P<0.01).Colocalization phenomenon existed between IL-18 and IL-18R.Skin IL-18 and IL-18R mRNA expression levels were significantly higher(P<0.01).Compared with model group,the skin appearance of the aerobic exercise and resistance exercise groups was significantly improved(P<0.05 or P<0.01).The thickness of the epidermis(P<0.05)and dermis increased significantly in resistance exercise group(P<0.01),and the elastic fibers were arranged in a more neat and orderly manner.The expression of P16 protein in the skin was decreased in aerobic exercise group(P<0.05).The levels of serum TNF-α,and serum and skin IL-18 were decreased in aerobic exercise group(P<0.05).The levels of serum and skin IL-1β,TNF-α and IL-18 in the resistance ex-ercise group were decreased(P<0.05 or P<0.01).Skin IL-18R content was significantly decreased in both aerobic and re-sistance exercise groups(P<0.01).IL-18BP content was significantly increased(P<0.01),and colocalized expression levels of IL-18 and IL-18R were significantly decreased.The mRNA expression of IL-18 and IL-18R was significantly de-creased in both aerobic and resistance exercise groups(P<0.01).CONCLUSION:Both aerobic and resistance exercise delay age-increased skin aging in rapidly aging mice,and the IL-18/IL-18R signaling pathway down-regulated by exercise may be the pathway of this effect.