@article {70488,
	title = {Form and function of actin impacts actin health and aging.},
	journal = {iScience},
	volume = {29},
	year = {2026},
	month = {2026 Sep 18},
	pages = {117256},
	abstract = {<p>The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin structure and function influence lifespan and various hallmarks of aging in . Whole-animal and tissue-specific knockdown of actin and key actin-binding proteins (ABPs)- (Arp2/3), (cofilin), and (tropomyosin)-led to premature disruption of filament organization, reduced lifespan, and tissue-specific physiological defects. Actin dysfunction also displayed a more "aged" transcriptome using previously validated transcriptomics clocks, and broadly exacerbated many age-associated phenotypes, including mitochondrial dysfunction, lipid dysregulation, loss of proteostasis, impaired autophagy, and intestinal barrier failure. Pharmacological destabilization with Latrunculin A mirrored genetic knockdowns, while mild stabilization with Jasplakinolide modestly extended lifespan, emphasizing that optimal and finely tuned actin function is critical for healthy aging. Finally, analysis of human genome-wide association data revealed that common polymorphisms correlate with differences in age-related decline in gait speed, suggesting some links between aging and actin across organisms. Taken together, our results provide a comprehensive and publicly accessible resource that maps, for the first time, how changes in actin integrity correlate with diverse aging phenotypes across tissues. This descriptive framework is intended to enable future mechanistic discovery by offering a deep, unbiased dataset that can be integrated with emerging studies to define how actin dynamics can potentially influence aging.</p>
},
	issn = {2589-0042},
	doi = {10.1016/j.isci.2026.117256},
	url = {https://doi.org/10.1016/j.isci.2026.117256},
	author = {Averbukh, Maxim and Nelson, Hunter T and Wang, Tiffany and Lange, Caitlin M and Alcala, Athena and Kim, Juri and Suh, Daniella and Vega, Matthew and Gao, Shihong Max and Dutta, Naibedya and Young, Khristina E and Aviles Barahona, Rebecca and Coakley, Aeowynn J and Gerke, Joe A and Odron, Sofia F and Clarke, Jacqueline G and Singh, Navjot and Nickel, Matthew S and Peterson, Jacob C and Lam-Truong, Hannah L and Moaddeli, Darius and Castro Torres, Toni and Oorloff, Maria and Peruch, Melissa and Nair, Tripti and Mehta, Hemal H and Thorwald, Max A and Ono, Shoichiro and Curran, Sean P and Wang, Meng C and Benayoun, B{\'e}r{\'e}nice A and Hill, Cristal M and Johnson, Tyler A and Crimmins, Eileen M and Arpawong, Thalida Em and Kumsta, Caroline and Garcia, Gilberto and Higuchi-Sanabria, Ryo}
}
