Polysaccharide is one of the main active ingredients in Lonicera japonica Thunb. (L. japonica). In this study, we examined the anti-aging activities of L.japonica polysaccharides (LJPs) and further explored the mechanisms. Polysaccharides from L.japonica including the crude LJP (CLJP) and the purified fraction (LJP-2-1) were characterized. The molecular weights of CLJP and LJP-2-1 were 1450 kDa and 1280 kDa, respectively. Meanwhile, CLJP was mainly composed of galacturonic acid (23.57 %), galactose (23.45 %) and arabinose (23.45 %). LJP-2-1 was mainly composed of galacturonic acid (51.25 %) and arabinose (22.89 %). In Caenorhabditis elegans (C. elegans), LJPs maximally prolonged mean lifespan by 13.97 %, promoted fitness with increased motility by 40.92 % and pharyngeal pumping by 25.72 %, and decreased lipofuscin accumulation by 38.9 % with intact body length and fecundity. Moreover, CLJP extended the mean lifespan of nematodes under oxidative and heat stress by 16.76 % and 14.05 % respectively by activating stress-related genes and the antioxidant system. Further, CLJP required DAF-16 to prolong the lifespan of nematodes. CLJP upregulated the expression of daf-16 and its targeted downstream genes, including sod-3, gst-4 and hsp-16.2. Moreover, nuclear accumulation of DAF-16 was promoted upon CLJP treatment. Together, our data uncover the role of LJPs in extending lifespan and healthspan through DAF-16.

Proper telomere length is essential for indefinite self-renewal of embryonic stem (ES) cells and cancer cells. Telomerase-deficient late generation mouse ES cells and human ALT cancer cells are able to propagate for numerous passages, suggesting telomerase-independent mechanisms responding for telomere maintenance. However, the underlying mechanisms ensuring the telomere length maintenance are unclear. Here, using late generation telomerase KO (G4 Terc^-/-) ESCs as a model, we show that Zscan4, highly upregulated in G4 Terc^-/- ESCs, is responsible for the prolonged culture of these cells with stably short telomeres. Mechanistically, G4 Terc^-/- ESCs showed reduced levels of DNA methylation and H3K9me3 at Zscan4 promoter and subtelomeres, which relieved the expression of Zscan4. Similarly, human ZSCAN4 was also derepressed by reduced H3K9me3 at its promoter in ALT U2 OS cells, and depletion of ZSCAN4 significantly shortened telomeres. Our results define a similar conserved pathway contributing to the telomere maintenance in telomerase-deficient late generation mESCs and human ALT U2OS cancer cells.

Muscle stem cells (MuSCs) isolated ex vivo are essential original cells to produce cultured meat. Currently, one of the main obstacles for cultured meat production derives from the limited capacity of large-scale amplification of MuSCs, especially under high-density culture condition. Here, we show that at higher cell densities, proliferation and differentiation capacities of porcine MuSCs are impaired. We investigate the roles of Hippo-YAP signaling, which is important regulators in response to cell contact inhibition. Interestingly, abundant but not functional YAP proteins are accumulated in MuSCs seeded at high density. When treated with lysophosphatidic acid (LPA), the activator of YAP, porcine MuSCs exhibit increased proliferation and elevated differentiation potential compared with control cells. Moreover, constitutively active YAP with deactivated phosphorylation sites, but not intact YAP, promotes cell proliferation and stemness maintenance of MuSCs. Together, we reveal a potential molecular target that enables massive MuSCs expansion for large-scale cultured meat production under high-density condition.