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Studies have found that salidroside, isolated from Rhodiola rosea L, has various pharmacological activities, but there have been no studies on the effects of salidroside on brain hippocampal senescence. The purpose of this study was to investigate the mechanistic role of salidroside in hippocampal neuron senescence and injury. In this study, long-term cultured primary rat hippocampal neurons and naturally aged C57 mice were treated with salidroside. The results showed that salidroside increased the viability and MAP2 expression, reduced β-galactosidase (β-gal) levels of rat primary hippocampal neurons. Salidroside also improved cognition dysfunction in ageing mice and alleviated neuronal degeneration in the ageing mice CA1 region. Moreover, salidroside decreased the levels of oxidative stress and p21, p16 protein expressions of hippocampal neurons and ageing mice. Salidroside promoted telomerase reverse transcriptase (TERT) protein expression via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway. In conclusion, our findings suggest that salidroside has the potential to be used as a therapeutic strategy for anti-ageing and ageing-related disease treatment. [ABSTRACT FROM AUTHOR]

Telomerase is a large ribonucleoprotein complex that contains a catalytic telomerase reverse transcriptase (TERT) and an RNA template. Telomerase activity is tightly controlled by TERT expression, which is regulated at both the transcriptional and post-translational levels. However, the detailed molecular mechanisms of telomerase regulation and function are not fully understood. To identify cofactors that contribute to telomerase regulation, we employed a yeast two-hybrid system to screen for hTERT-interacting proteins, using the hTERT T-motif as bait. We identify C53 as a novel hTERT interaction partner. We show that C53 interacts with hTERT both in vivo and in vitro. C53 depletion increases telomerase activity, and C53 overexpression inhibits telomerase activity in MCF7 cells. In addition, the C53 leucine zipper domain (amino acids 301-400) is required for interaction with hTERT. Deleting the leucine zipper domain eliminates C53 interaction with hTERT and abrogates its inhibitory effect on telomerase activity. Taken together, our results demonstrate that C53 is a novel hTERT-associated protein that negatively regulates telomerase activity. [ABSTRACT FROM AUTHOR]

Telomerase is aberrantly expressed in many cancers and plays an important role in the development of cellular immortality and oncogenesis, which makes it a potential cancer therapeutic target for drug discovery. Here, we constructed a firefly luciferase reporter driven by the human telomerase reverse trancriptase ( hTERT ) gene promoter to screen for inhibitory compounds. Compound 5c was discovered and shown to significantly inhibit the promoter activity of hTERT gene. Furthermore, five analogs of compound 5c were synthesized, and compound 8b was shown to be a more potent inhibitor of hTERT gene promoter activity and subsequent expression of hTERT mRNA and protein. The viability of HeLa cells was inhibited by a knockdown of hTERT gene expression, and the same effect was also observed by treating with compound 8b . Moreover, our results indicated that compound 8b induced apoptosis of HeLa cells, and activated caspase-9 and caspase-3 enzymes. Taken together, these results suggested that compound 8b down-regulates the expression of hTERT and induces mitochondrial-dependent apoptosis. [ABSTRACT FROM AUTHOR]