Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction
Lipoic acid rejuvenates aged intestinal stem cells by preventing age-associated endosome reduction
复制标题
硫辛酸通过防止与年龄相关的内体减少来恢复衰老的肠道干细胞的活力
DOI：
10.15252/embr.201949583
复制
发表时间：
2020-07-09
期刊：
影响因子：
7.7
通讯作者：
Chen, Haiyang
中科院分区：
文献类型：
--
作者：
Du, Gang;Qiao, Yicheng;Chen, Haiyang
成人干细胞功能的年龄相关性下降与组织功能下降和年龄相关疾病密切相关。然而，最终导致观察到的干细胞功能衰退的潜在机制仍然在很大程度上仍未被探索。这项研究调查了果蝇的肠道，发现随着年龄的增长，硫辛酸合成酶持续下调，硫辛酸合成酶编码内源性合成α-硫辛酸(ALA)的关键酶。重要的是，口服ALA显著逆转了与年龄相关的肠道干细胞(ISCs)的过度增殖和所观察到的肠道功能的下降，从而延长了果蝇的寿命。本研究报告，ALA通过促进内吞-自噬网络的激活来逆转与年龄相关的ISC功能障碍，内吞-自噬网络在衰老的ISCs中减少。此外，本研究表明ALA可作为一种安全有效的抗衰老化合物，用于治疗与ISC功能障碍相关的疾病，促进人类的健康衰老。
The age-associated decline of adult stem cell function is closely related to the decline in tissue function and age-related diseases. However, the underlying mechanisms that ultimately lead to the observed functional decline of stem cells still remain largely unexplored. This study investigatedDrosophilamidguts and found a continuous downregulation oflipoic acid synthase, which encodes the key enzyme for the endogenous synthesis of alpha-lipoic acid (ALA), upon aging. Importantly, orally administration ofALAsignificantly reversed the age-associated hyperproliferation of intestinal stem cells (ISCs) and the observed decline of intestinal function, thus extending the lifespan ofDrosophila. This study reports thatALAreverses age-associatedISCdysfunction by promoting the activation of the endocytosis-autophagy network, which decreases in agedISCs. Moreover, this study suggests thatALAmay be used as a safe and effective anti-aging compound for the treatment ofISC-dysfunction-related diseases and for the promotion of healthy aging in humans.