Ren Li-Li, Miao Hua, Wang Yan-Ni, Liu Fei, Li Ping, Zhao Ying-Yong
School of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Department of Urology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Aging Dis. 2023 Oct 1;14(5):1633-1650. doi: 10.14336/AD.2023.0222.
Fibrosis is the abnormal accumulation of extracellular matrix proteins such as collagen and fibronectin. Aging, injury, infections, and inflammation can cause different types of tissue fibrosis. Numerous clinical investigations have shown a correlation between the degree of liver and pulmonary fibrosis in patients and telomere length and mitochondrial DNA content, both of which are signs of aging. Aging involves the gradual loss of tissue function over time, which results in the loss of homeostasis and, ultimately, an organism's fitness. A major feature of aging is the accumulation of senescent cells. Senescent cells abnormally and continuously accumulate in the late stages of life, contributing to age-related fibrosis and tissue deterioration, among other aging characteristics. Furthermore, aging generates chronic inflammation, which results in fibrosis and decreases organ function. This finding suggests that fibrosis and aging are closely related. The transforming growth factor-beta (TGF-β) superfamily plays a crucial role in the physiological and pathological processes of aging, immune regulation, atherosclerosis, and tissue fibrosis. In this review, the functions of TGF-β in normal organs, aging, and fibrotic tissues is discussed: TGF-β signalling is altered with age and is an indicator of pathology associated with tissue fibrosis. In addition, this review discusses the potential targeting of noncoding.
纤维化是细胞外基质蛋白如胶原蛋白和纤连蛋白的异常积累。衰老、损伤、感染和炎症可导致不同类型的组织纤维化。大量临床研究表明，患者肝脏和肺纤维化程度与端粒长度和线粒体DNA含量之间存在相关性，而这两者都是衰老的标志。衰老涉及组织功能随时间逐渐丧失，这会导致体内稳态失衡，最终影响生物体的健康状况。衰老的一个主要特征是衰老细胞的积累。衰老细胞在生命后期异常且持续积累，导致与年龄相关的纤维化和组织退化等衰老特征。此外，衰老会引发慢性炎症，进而导致纤维化并降低器官功能。这一发现表明纤维化与衰老密切相关。转化生长因子-β（TGF-β）超家族在衰老、免疫调节、动脉粥样硬化和组织纤维化的生理和病理过程中起着关键作用。在本综述中，将讨论TGF-β在正常器官、衰老和纤维化组织中的功能：TGF-β信号通路随年龄变化，是与组织纤维化相关病理的一个指标。此外，本综述还讨论了非编码的潜在靶向作用。
