Laboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, Belgrade, Serbia.
Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Institute for Mitochondrial Diseases and Ageing, Medical Faculty, University of Cologne, Cologne, Germany.
Aging (Albany NY). 2021 Mar 26;13(6):8040-8054. doi: 10.18632/aging.202885.
Gut homeostasis is maintained by the close interaction between commensal intestinal microbiota and the host, affecting the most complex physiological processes, such as aging. Some commensal bacteria with the potential to promote healthy aging arise as attractive candidates for the development of pro-longevity probiotics. Here, we showed that heat-inactivated human commensal BGHV110 (BGHV110) extends the lifespan of and improves age-related physiological features, including locomotor function and lipid metabolism. Mechanistically, we found that BGHV110 promotes HLH-30/TFEB-dependent autophagy to delay aging, as longevity assurance was completely abolished in the mutant lacking HLH-30, a major autophagy regulator in . Moreover, we observed that BGHV110 partially decreased the content of lipid droplets in an HLH-30-dependent manner and, at the same time, slightly increased mitochondrial activity. In summary, this study demonstrates that specific factors from commensal bacteria can be used to exploit HLH-30/TFEB-mediated autophagy in order to promote longevity and fitness of the host.
肠道内稳态是由共生肠道微生物群与宿主的密切相互作用维持的，影响着最复杂的生理过程，如衰老。一些具有促进健康衰老潜力的共生菌成为开发长寿命益生菌的有吸引力的候选物。在这里，我们表明，热灭活的人类共生菌 BGHV110（BGHV110）延长了 和 的寿命，并改善了与年龄相关的生理特征，包括运动功能和脂质代谢。在机制上，我们发现 BGHV110 通过 HLH-30/TFEB 依赖性自噬来促进衰老，因为在缺乏 HLH-30 的突变体中，HLH-30 是 的主要自噬调节剂，其长寿保证完全被废除。此外，我们观察到 BGHV110 以 HLH-30 依赖的方式部分降低脂滴的含量，同时略微增加线粒体活性。总之，这项研究表明，共生菌的特定因素可以被用来利用 HLH-30/TFEB 介导的自噬来促进宿主的长寿和适应性。
