Lack of T04C9.1 , the Homologue of Mammalian APPL2, Leads to Premature Ageing and Shortens Lifespan in Caenorhabditis elegans

• Published in: Genes Vol. 15; no. 6; p. 659
• Main Authors: Li, Zirui, Chen, Zhiqiang, Zhao, Lianghao, Sun, Jiaqi, Yin, Lin, Jiang, Yuwei, Shi, Xiaotong, Song, Ziye, Zhang, Lu
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22.05.2024; MDPI
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; ageing; Aging; Aging - genetics; Aging, Premature - genetics; Animals; APPL2; Autophagy; Autophagy - genetics; C. elegans; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cardiovascular diseases; Cloning; E coli; Endothelial cells; Human Umbilical Vein Endothelial Cells; Humans; Insulin; Laboratory animals; Life span; lifespan; Longevity - genetics; Mice; Nematodes; Nervous system diseases; Physiology; Plasmids; Proteins; Rapamycin; Risk factors; Senescence; T04C9.1; Umbilical cord; Umbilical vein; China; Germany; United States > US; T04C9.1; C. elegans; ageing; autophagy; lifespan; APPL2
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes15060659

Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that the level of APPL2, an adaptor protein, is significantly reduced in the major organs of aged mice. Knocking down APPL2 causes premature ageing of human umbilical vein endothelial cells (HUVECs). We find that a lack of , the homologue of mammalian APPL2, leads to premature ageing, slow movements, lipid deposition, decreased resistance to stresses, and shortened lifespan in ( ), which are associated with decreased autophagy. Activating autophagy by rapamycin or inhibition of suppresses the age-related alternations, impaired motility, and shortened lifespan of , which are reversed by knocking down autophagy-related genes. Our work provides evidence that APPL2 and its homologue decrease with age and reveals that a lack of bridges autophagy decline and ageing in .