In roundworms, disruption of the actin cytoskeleton, a network of protein filaments inside cells, shortened lifespan, while mild stabilization of the network extended it
In roundworms, disruption of the actin cytoskeleton, a network of protein filaments inside cells, shortened lifespan, while mild stabilization of the network extended it
On August 24, Crossref added a bibliographic record for an iScience article. In the full text, the authors altered actin cytoskeleton function in the roundworm Caenorhabditis elegans. Disrupting the network shortened lifespan, while mild chemical stabilization extended it. A high dose had the opposite effect.
The actin cytoskeleton enables muscle contraction, maintains connections between intestinal cells, and supports intracellular transport. In an earlier study from the same line of research, increased production of the BET-1 protein preserved actin organization in old roundworms and extended their lifespan. The new study examines what happens when the network loses its organization.
The authors separately reduced the function of actin itself and three proteins that control the assembly, disassembly, and anchoring of actin filaments. In muscle, the intestine, and the outer covering of the roundworm, the filaments lost their normal organization earlier, and mobility declined at older ages. In some roundworms, gene activity came to resemble the profile seen in older animals.
In roundworms, the age at which an intervention begins can change its effect. In another experiment in C. elegans, brief suppression of NuA4 during early development extended lifespan, whereas intervention later in life shortened it. The authors therefore began some experiments in the new study on the first day of adulthood. Suppression of arx-2, a component of the Arp2/3 complex that builds branched actin networks, still consistently shortened lifespan under these conditions.
In a separate experiment, the researchers gave adult roundworms two compounds. Latrunculin A disassembles actin filaments and shortened lifespan as the dose increased. Jasplakinolide promotes filament assembly and stabilization. It extended lifespan at low concentrations and shortened it at high concentrations. The authors propose that high doses are harmful because excessively stabilized filaments cannot reorganize as readily.
Actin disruption also altered mitochondrial shape and function, protein quality control, the recycling of cellular components, and the integrity of the intestinal barrier. In two independent human cohorts, the authors also compared ACTB gene variants with the rate of age-related decline in walking speed.