Department of Molecular and Cell Biology, Howard Hughes Medical Institute, and.
The Glenn Center for Aging Research, University of California, Berkeley, Berkeley, CA 94720.
Mol Biol Cell. 2018 Oct 15;29(21):2522-2527. doi: 10.1091/mbc.E18-06-0362. Epub 2018 Aug 22.
There are many studies suggesting an age-associated decline in the actin cytoskeleton, and this has been adopted as common knowledge in the field of aging biology. However, a direct identification of this phenomenon in aging multicellular organisms has not been performed. Here, we express LifeAct::mRuby in a tissue-specific manner to interrogate cytoskeletal organization as a function of age. We show for the first time in Caenorhabditis elegans that the organization and morphology of the actin cytoskeleton deteriorate at advanced age in the muscles, intestine, and hypodermis. Moreover, hsf-1 is essential for regulating cytoskeletal integrity during aging, so that knockdown of hsf-1 results in premature aging of actin and its overexpression protects actin cytoskeletal integrity in the muscles, the intestine, and the hypodermis. Finally, hsf-1 overexpression in neurons alone is sufficient to protect cytoskeletal integrity in nonneuronal cells.
有许多研究表明，肌动蛋白细胞骨架会随着年龄的增长而衰退，这在衰老生物学领域已被视为常识。然而，衰老多细胞生物中这一现象的直接鉴定尚未进行。在这里，我们以组织特异性的方式表达 LifeAct::mRuby，以研究细胞骨架组织作为年龄的函数。我们首次在秀丽隐杆线虫中表明，肌动蛋白细胞骨架的组织和形态在肌肉、肠道和皮下组织中随着年龄的增长而恶化。此外，hsf-1 对于调节衰老过程中的细胞骨架完整性是必不可少的，因此 hsf-1 的敲低导致肌动蛋白的过早衰老，而过表达 hsf-1 则可保护肌肉、肠道和皮下组织中肌动蛋白细胞骨架的完整性。最后，神经元中 hsf-1 的过表达足以保护非神经元细胞的细胞骨架完整性。
