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模拟微重力加速酿酒酵母衰老。

Simulated microgravity accelerates aging in Saccharomyces cerevisiae.

机构信息

Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, São Paulo, Brazil.

Departamento de Química Fundamental - Instituto de Química, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Life Sci Space Res (Amst). 2021 Feb;28:32-40. doi: 10.1016/j.lssr.2020.12.003. Epub 2020 Dec 31.

Abstract

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.

摘要

人体在微重力环境下会经历生理变化,这些变化与地球上的衰老过程相似。这些变化包括早期骨质疏松症、骨骼肌萎缩、心脏功能障碍和免疫衰老等,这些对太空环境的适应可能会对载人火星任务构成一些风险。为了研究微重力对衰老的影响,许多模式生物如秀丽隐杆线虫、黑腹果蝇和小鼠被用于研究。在此,我们报告在旋转器中模拟微重力条件下,酿酒酵母的复制寿命(RLS)会降低。酵母寿命的缩短不是由于对热休克或氧化应激的耐受性降低所致,并且可以通过删除 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的 RLS。删除 SIR2 基因会加重模拟微重力对 RLS 的影响,并且与 fob1Δ 突变体表型一起表明,模拟微重力增强了额外染色质 rDNA 环的形成,这些环在酵母衰老过程中积累。我们还表明,当细胞在旋转器中生长时,在最小培养基中的时序寿命没有改变。我们的数据表明,由于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载人太空任务以及将微重力作为人类衰老模型的应用具有潜在意义。

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