Regulation of DNA damage signaling by autophagy in senescence.

衰老过程中自噬对 DNA 损伤信号的调节。

• 批准号: BB/K017233/1
• 负责人: Peter Adams
• 金额: $ 42.58万
• 依托单位: University of Glasgow
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK017233%2F1
• 关键词: Regulation; DNA; damage; signaling; autophagy

Cell senescence is a stable proliferation arrest of damaged cells that prevents the onset of cancer. Paradoxically, cell senescence can also contribute to tissue ageing, by preventing tissue renewal and causing tissue inflammation. Triggers of cell senescence include DNA damage and dysfunctional mitochondria (sites of cellular energy production). Appropriate healthy ageing (i.e. a healthy lifespan without cancer) depends on appropriate balance of the senescence program. Autophagy is a cellular recycling process that degrades and eliminates damaged structures from the cell. Our preliminary data indicates that autophagy serves to suppress accumulation of DNA damage and dysfunctional mitochondria in the cell. Hence, we hypothesise that autophagy controls - and perhaps dampens - onset and/or maintenance of cell senescence, and so tissue and organismal ageing. By exploiting the complementary strengths of Drs. Passos and Adams we will investigate this hypothesis in cell culture and mouse models. Progress in these studies will facilitate development of biomarkers of interventions to promote healthy ageing.

细胞衰老是受损细胞的稳定增殖停滞，可防止癌症的发生。特别地，细胞衰老也可以通过阻止组织更新和引起组织炎症而导致组织老化。细胞衰老的触发因素包括DNA损伤和线粒体功能障碍（细胞能量产生的部位）。适当的健康老龄化（即没有癌症的健康寿命）取决于衰老计划的适当平衡。自噬是一种细胞循环过程，可以降解并消除细胞中受损的结构。我们的初步数据表明，自噬有助于抑制细胞中DNA损伤和线粒体功能障碍的积累。因此，我们假设自噬控制-也许抑制-细胞衰老的发生和/或维持，因此组织和生物体衰老。通过利用帕索斯博士和亚当斯博士的互补优势，我们将在细胞培养和小鼠模型中研究这一假设。这些研究的进展将有助于开发促进健康老龄化的干预措施的生物标志物。

项目成果

Mitochondria are required for pro-ageing features of the senescent phenotype.

• DOI: 10.15252/embj.201592862
• 发表时间: 2016-04-01
• 期刊: The EMBO journal
• 作者: Correia-Melo C;Marques FD;Anderson R;Hewitt G;Hewitt R;Cole J;Carroll BM;Miwa S;Birch J;Merz A;Rushton MD;Charles M;Jurk D;Tait SW;Czapiewski R;Greaves L;Nelson G;Bohlooly-Y M;Rodriguez-Cuenca S;Vidal-Puig A;Mann D;Saretzki G;Quarato G;Green DR;Adams PD;von Zglinicki T;Korolchuk VI;Passos JF
• 通讯作者: Passos JF

Aging-Induced Stem Cell Mutations as Drivers for Disease and Cancer.

• DOI: 10.1016/j.stem.2015.05.002
• 发表时间: 2015-06-04
• 期刊: Cell stem cell
• 影响因子: 23.9
• 作者: Adams PD;Jasper H;Rudolph KL
• 通讯作者: Rudolph KL