Information Processing Biology Unit, Okinawa Institute of Science and Technology Graduate University, Onna-son, Kunigami-gun, Okinawa, Japan.
Aging (Albany NY). 2020 Dec 3;12(23):23525-23547. doi: 10.18632/aging.202296.
Some genes are essential for survival, while other genes play modulatory roles on health and survival. Genes that play modulatory roles may promote an organism's survival and health by fine-tuning physiological processes. An unbiased search for genes that alter an organism's ability to maintain aspects of health may uncover modulators of lifespan and healthspan. From an unbiased screen for mutants that show a progressive decline in motility, we aimed to identify genes that play a modulatory role in maintenance of locomotor healthspan. Here we report the involvement of encoding a class I histone deacetylase, as a genetic factor that contributes in the maintenance of general health and locomotion in . We identified a missense mutation in HDA-3 as the causative mutation in one of the isolated strains that show a progressive decline in maximum velocity and travel distance. From transcriptome analysis, we found a cluster of genes on Chromosome II carrying BATH domains that were downregulated by . Furthermore, downregulation of individual genes leads to significant decline in motility. Our study identifies genetic factors that modulate the maintenance of locomotor healthspan and may reveal potential targets for delaying age-related locomotor decline.
有些基因对生存是必需的，而其他基因则对健康和生存起着调节作用。发挥调节作用的基因可以通过微调生理过程来促进生物体的生存和健康。对改变生物体维持健康方面能力的基因进行无偏搜索，可能会发现寿命和健康跨度的调节剂。从一个针对运动能力逐渐下降的 突变体的无偏筛选中，我们旨在鉴定在维持运动健康跨度方面起调节作用的基因。在这里，我们报告了编码一类组蛋白去乙酰化酶的 基因作为遗传因素的参与，该基因有助于 的一般健康和运动。我们在一个表现出最大速度和行进距离逐渐下降的分离株中发现了 HDA-3 的一个错义突变，这是导致这种情况的致病突变。从转录组分析中，我们在染色体 II 上发现了一个携带 BATH 结构域的基因簇，这些基因被 下调。此外，个别 基因的下调会导致运动能力显著下降。我们的研究确定了调节运动健康跨度维持的遗传因素，这可能揭示了延缓与年龄相关的运动能力下降的潜在目标。
