Salidroside Delays Cellular Senescence by Stimulating Mitochondrial Biogenesis Partly through a miR-22/SIRT-1 Pathway.

Calorie restriction (CR) is a nongenetic intervention with a robust effect on delaying aging in mammals and other organisms. A mild stimulation on mitochondrial biogenesis induced by CR seems to be an important action mode for its benefits. Here, we reported that a component isolated from Rhodiola rosea L., salidroside, delays replicative senescence in human fibroblasts, which is related to its stimulation on mitochondrial biogenesis by activating SIRT1 partly resulted from inhibition on miR-22. Salidroside increased the mitochondrial mass that accompanied an increment of the key regulators of mitochondrial biogenesis including PGC-1α, NRF-1, and TFAM and reversed the mitochondrial dysfunction in presenescent 50PD cells, showing a comparable effect to that of resveratrol. SIRT1 is involved in the inducement of mitochondrial biogenesis by salidroside. The declined expression of SIRT1 in 50PD cells compared with the young 30PD cells was prevented upon salidroside treatment. In addition, pretreatment of EX-527, a selective SIRT1 inhibitor, could block the increased mitochondrial mass and decreased ROS production induced by salidroside in 50PD cells, resulting in an accelerated cellular senescence. We further found that salidroside reversed the elevated miR-22 expression in presenescent cells according to a miRNA array analysis and a subsequent qPCR validation. Enforced miR-22 expression by using a Pre-miR-22 lentiviral construct induced the young fibroblasts (30PD) into a senescence state, accompanied with increased senescence-related molecules including p53, p21, p16, and decreased SIRT1 expression, a known target of miR-22. However, salidroside could partly impede the senescence progression induced by lenti-Pre-miR-22. Taken together, our data suggest that salidroside delays replicative senescence by stimulating mitochondrial biogenesis partly through a miR22/SIRT1 pathway, which enriches our current knowledge of a salidroside-mediated postpone senility effect and provides a new perspective on the antidecrepitude function of this naturally occurring compound in animals and humans.

Antiaging effect of pine pollen in human diploid fibroblasts and in a mouse model induced by D-galactose.

The present paper was designed to investigate the effect of pine pollen against aging in human diploid fibroblast 2BS cells and in an accelerated aging model, which was established by subcutaneous injections with D-galactose daily for 8 weeks in C57BL/6J mice. Pine pollen (1 mg/mL and 2 mg/mL) is proved to delay the replicative senescence of 2BS cells as evidenced by enhanced cell proliferation, decreased SA-ß-Gal activity, and reversed expression of senescence-associated molecular markers, such as p53, p21(Waf1), p16(INK4a), PTEN, and p27(Kip1) in late PD cells. Besides, pine pollen reversed D-galactose-induced aging effects in neural activity and inflammatory cytokine levels, as indicated by improved memory latency time and reduced error rate in step-down test and decreased concentrations of IL-6 and TNF-α in model mice. Similar to the role of AGEs (advanced glycation endproducts) formation inhibitor aminoguanidine (AG), pine pollen inhibited D-galactose-induced increment of AGEs levels thus reversed the aging phenotypes in model mice. Furthermore, the declined antioxidant activity was obviously reversed upon pine pollen treatment, which may account for its inhibitory effect on nonenzymatic glycation (NEG) in vivo. Our finding presents pine pollen as an attractive agent with potential to retard aging and attenuate age-related diseases in humans.