2018
DOI: 10.1080/15384101.2018.1554781
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Abstract: Rapamycin inhibits cell proliferation, yet preserves (re)-proliferative potential (RPP). RPP is a potential of quiescent cells that is lost in senescent cells. mTOR drives conversion from quiescence to senescence (geroconversion). By suppressing geroconversion, rapamycin preserves RPP. Geroconversion is characterized by proliferation-like levels of phospho-S6K/S6/4E-BP1 in nonproliferating cells arrested by p16 and/or p21. mTOR-driven geroconversion is associated with cellular hyperfunction, which in turn lead… Show more

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Cited by 49 publications
(63 citation statements)
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“…As shown in Supplementary Figure 2A-2C, knockdown or inhibition of PRMT5 showed little effect on the apoptosis of U2 OS cells. However, knockdown of PRMT5 significantly increased the percentage of senescent cells and retarded the cell proliferation of OS, as evidenced by SA-β-gal staining, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay, as well as the protein expression of p-mTOR and p-p70 S6K, which distinguish quiescence and senescence [27] (Figure 2A and 2B, Supplementary Figure 2D-2F). Senescent cells have been demonstrated to actively secrete a group of proteins named SASP [28]; and we confirmed that knockdown of PRMT5 upregulated the mRNA expression of SASP genes, including CXCL-1, CXCL-2, CXCL-3, IL-6, IL-8, TNF-α, ICAM-1, and CCL2 (Supplementary Figure 2G).…”
Section: Downregulation Of Prmt5 Elicits Senescence In Os Cellsmentioning
confidence: 97%
“…As shown in Supplementary Figure 2A-2C, knockdown or inhibition of PRMT5 showed little effect on the apoptosis of U2 OS cells. However, knockdown of PRMT5 significantly increased the percentage of senescent cells and retarded the cell proliferation of OS, as evidenced by SA-β-gal staining, 5-Ethynyl-2'-deoxyuridine (EdU) incorporation assay, as well as the protein expression of p-mTOR and p-p70 S6K, which distinguish quiescence and senescence [27] (Figure 2A and 2B, Supplementary Figure 2D-2F). Senescent cells have been demonstrated to actively secrete a group of proteins named SASP [28]; and we confirmed that knockdown of PRMT5 upregulated the mRNA expression of SASP genes, including CXCL-1, CXCL-2, CXCL-3, IL-6, IL-8, TNF-α, ICAM-1, and CCL2 (Supplementary Figure 2G).…”
Section: Downregulation Of Prmt5 Elicits Senescence In Os Cellsmentioning
confidence: 97%
“…Lupus and Sjogren's syndrome occur when mTOR is activated, and its blockade with rapamycin is therapeutically effective [70]. Recent investigations have demonstrated that both mTOR and rapamycin have pivotal roles of antiaging, development, various diseases such as cancer, diabetes, obesity and also tissue injury [71][72][73][74][75][76]. Aging is a continuation of developmental growth [75], and rapamycin slows aging by inhibitory effects on mTOR driving conversion from quiescence to senescence (geroconversion) [76,77].…”
Section: Discussionmentioning
confidence: 99%
“…The theory of hyperfunctional aging [2532] addresses this paradox. Killing senescent cells is beneficial because senescent cells are hyperfunctional [33]. The hypersecretory phenotype or Senescence-Associated Secretory Phenotype (SASP) is the best-known example of universal hyperfunction [3436].…”
mentioning
confidence: 99%
“…Senolytics should not be confused with gerosuppressants (Figure 1). Gerosuppressants, such as rapamycin, do not kill cells; they instead prevent cellular conversion to senescence (geroconversion) [33]. Rapamycin also slows disease progression by limiting the hyperfunction of senescent cells.…”
mentioning
confidence: 99%
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