Targeting cellular senescence in adipose tissue: a potential treatment for type 2 diabetes...International Society for Gerontechnology 13th World Conference, October 22-26, 2022, Daegu, South Korea
Purpose Cellular senescence refers to the cessation of cell proliferation that can be triggered by endogenous and exogenous stimuli, such as telomere dysfunction, DNA damage, and oncogenic gene expression (Di Micco et al, 2021). Senescent cells release senescent-associated secretory phenotype (SASP)...
| Publicado en: | Gerontechnology Vol. 21; pp. 2 - 3 |
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| Autores principales: | , , , , |
| Formato: | abstract proceedings research Journal Article |
| Publicado: |
International Society for Gerontechnology
Oct2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=161396074&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 161396074 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 15691101 904R jtl: Gerontechnology issn: 15691101 maglogo: N pubinfo: dt: Oct2022 vid: 21 pid: 54298 pub: International Society for Gerontechnology artinfo: ui: 161396074 161396074 161396074 10.4017/gt.2022.21.s.808.2.sp3 161396074 ppf: 2 ppct: 1 formats: tig: atl: Targeting cellular senescence in adipose tissue: a potential treatment for type 2 diabetes...International Society for Gerontechnology 13th World Conference, October 22-26, 2022, Daegu, South Korea aug: au: Jung, H. B. Kim, E. C. Sung, H. K. Kim, J. R. Park, S. Y. affil: Senotherapy-based Metabolic Disease Control Research Center, College of Medicine, Yeungnam University, Daegu, South Korea sug: subj: Diabetes Mellitus, Type 2 Therapy Cell Aging Adipose Tissue Senotherapeutics Insulin Resistance Congresses and Conferences South Korea South Korea ab: Purpose Cellular senescence refers to the cessation of cell proliferation that can be triggered by endogenous and exogenous stimuli, such as telomere dysfunction, DNA damage, and oncogenic gene expression (Di Micco et al, 2021). Senescent cells release senescent-associated secretory phenotype (SASP), which turns neighboring normal cells into senescent cells. As the accumulation of senescent cells compromises tissue repair and function, cellular senescence eventually leads to tissue aging and aging-related chronic diseases, including type 2 diabetes. Therefore, killing the senescent cells (senolytics) or reversing the senescent cells to young cells (senomorphics) can prevent or alleviate aging and aging-associated diseases (Niedernhofer and Robbins 2018). Recently, previous studies showed the reduction in senescent cells in adipose tissue attenuates insulin resistance in high-fat diet (HFD)-fed obese mice, suggesting that targeting cellular senescence in adipose tissue could be the potential treatment for type 2 diabetes (Smith et al 2021). Currently, however, there is no clinically available effective senotherapy. In our study, we aimed to find a novel senotherapy for adipose tissue aging and insulin resistance. Method We examined 2,150 clinically available compounds for their senolytic or senomorphic effect in human dermal fibroblast (HDF) by using cell toxicity or senescent-associated beta-galactosidase staining, respectively. Among the 10 compounds which were found to have a senolytic or senomorphic effect in HDF, one compound also attenuated senescence in human preadipocytes and 3T3-L1 adipocytes. The effects of the new senolytic agent (HT) on adipose tissue aging and insulin sensitivity were examined in high-fat diet-fed obese mice and aged mice. Results and Discussion HT attenuated weight gain and reduced fat mass in obese mice even though it did not affect food intake. It reduced adipose tissue aging both in obese mice and aged mice, which was followed by a reduction in large-sized adipocytes, the number of crown-like structures, and the levels of inflammatory cytokines. HT improved glycemic control and insulin resistance. It also reduced adipose tissue aging in human subcutaneous adipose tissue ex vivo. Thus, these results suggest that we have found a novel senolytic agent that may be a potential therapeutic for type 2 diabetes. pubtype: Academic Journal doctype: abstract proceedings research Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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