Research led by Sichuan University and Huazhong University of Science and Technology, China, has revealed genetic mechanisms that can prolong healthy aging. In the paper, titled “Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and prolongs health span,” published in PLoS Biologythe team detailed the methods they used to narrow down potential genomic pathways to a gene that may be critical to extending healthy human longevity.
With a combination of genetic manipulation, behavioral assays, microscopy techniques, and electrophysiology, the researchers investigated the role of VPS-34 in motor aging. These methods allowed researchers to gain insights into the molecular mechanisms underlying motor aging and the inhibitory effects of VPS-34 on motor function, synaptic transmission, and muscle integrity.
According to the authors, the increased life expectancy in recent decades has not been accompanied by a corresponding increase in health. Aging is characterized by the decline of many organs and tissues and motor aging, in particular, causes frailty, loss of motor independence, and other age-related issues. Identifying mechanisms for therapeutics to delay motor aging is important for promoting healthy aging.
The C. elegans worm is a widely used model for aging studies, and previous research has analyzed candidate genes involved in motor aging in worms and mice. Despite previous research efforts, knowledge of the evolutionarily conserved mechanisms controlling motor aging is still lacking. The team developed high-throughput screening methods to identify potential regulators of motor aging.
To start, the researchers tested the worms for good or bad health late in life. The worms were placed in a 1-cm-diameter circle on a culture plate, and after one hour, the percentage of worms that moved outside the circle (out-of-circle ratio) was measured. To assess the decline in motor activity during aging, the researchers monitored the worms from adulthood (day 1) to old age (day 9), measuring the ratio outside the circle every day.
The researchers compiled a list of potential gene targets by comparing worm gene expression through a genome-wide RNA interference (RNAi) screen. Through several rounds of screening, they identified several candidate genes that consistently increase motor activity when knocked down.
Among the top hits, they targeted the gene VPS-34 (human homolog PIK3C3) and found that its partial inhibition improved neuromuscular synaptic transmission and muscle integrity in worms and mice. Mice treated with a VPS-34 inhibitor performed better in the treadmill running assay.
The authors suggest that VPS-34 is an evolutionarily conserved regulator of motor aging and provides a potential actionable target for delaying motor aging and extending lifespan. Partial inhibition of VPS-34 may be a viable therapeutic strategy to improve motor function during aging. The study also highlights the importance of cell type-specific mechanisms, as VPS-34 primarily acts on motor neurons to regulate motor aging.
Future studies are needed to evaluate the functional outcomes after VPS-34 inhibition to better understand the benefits and harmful effects of any potential treatment strategy in the brain and other organs and types of cell.
For example, VPS-34 is known to be involved in a wide variety of cellular functions, including autophagy, which allows cells to recycle old or damaged parts and repair themselves. Prolonged restraint can lead to adverse effects on the organism’s health and vitality.
VPS-34 is conserved in all eukaryotes, and while signs of functional improvement may have been observed in the study scenario, more research is needed to fully understand the implications and potential risks. involved in the inhibition of VPS-34 in different contexts.
Zhongliang Hu et al, Partial inhibition of class III PI3K VPS-34 ameliorates motor aging and extends lifespan, PLoS Biology (2023). DOI: 10.1371/journal.pbio.3002165
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Citation: Inhibiting a gene leads to extended motor function longevity in C. elegans (2023, July 14) retrieved 14 July 2023 from https://phys.org/news/2023-07-inhibiting-gene-motor -function-longevity. html
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