The human body experiences physiological changes under microgravity environment that phenocopy aging on Earth. These changes include early onset osteoporosis, skeletal muscle atrophy, cardiac dysfunction, and immunosenescence, and such adaptations to the space environment may pose some risk to crewed missions to Mars. To investigate the effect of microgravity on aging, many model organisms have been used such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and mice. Herein we report that the budding yeast Saccharomyces cerevisiae show decreased replicative lifespan (RLS) under simulated microgravity in a clinostat. The reduction of yeast lifespan is not a result of decreased tolerance to heat shock or oxidative stress and could be overcome either by deletion of FOB1 or calorie restriction, two known interventions that extend yeast RLS. Deletion of the sirtuin gene SIR2 worsens the simulated microgravity effect on RLS, and together with the fob1Δ mutant phenotype, it suggests that simulated microgravity augments the formation of extrachromosomal rDNA circles, which accumulate in yeast during aging. We also show that the chronological lifespan in minimal medium was not changed when cells were grown in the clinostat. Our data suggest that the reduction in longevity due to simulated microgravity is conserved in yeast, worms, and flies, and these findings may have potential implications for future crewed missions in space, as well as the use of microgravity as a model for human aging.

人体在微重力环境下会经历生理变化，模仿地球上的衰老。这些变化包括早发性骨质疏松症、骨骼肌萎缩、心脏功能障碍和免疫衰老，这种对太空环境的适应可能会给载人火星任务带来一些风险。为了研究微重力对衰老的影响，已经使用了许多模型生物，例如线虫秀丽隐杆线虫、黑腹果蝇和小鼠。在本文中，我们报告了萌芽酵母酿酒酵母显示在模拟微重力下的回转仪中的复制寿命 (RLS) 减少。酵母寿命的缩短不是对热休克或氧化应激的耐受性降低的结果，可以通过删除FOB1或热量限制来克服，这两种已知的干预措施可以延长酵母 RLS。Sirtuin基因SIR2 的缺失加剧了模拟微重力对 RLS 的影响，并与fob1一起Δ 突变表型，这表明模拟微重力增加了染色体外 rDNA 环的形成，这些环在酵母中在老化过程中积累。我们还表明，当细胞在恒温器中生长时，基本培养基中的按时间顺序排列的寿命没有改变。我们的数据表明，模拟微重力导致的寿命缩短在酵母、蠕虫和苍蝇中是保守的，这些发现可能对未来的太空载人任务以及使用微重力作为人类衰老模型具有潜在影响。