Melo-Miranda Rita, Pinto Ana, Barreto Hugo C, Jesus Catarina S H, Gordo Isabel, Duarte Iola F, Sousa Ana
Institute of Biomedicine (iBiMED), Department of Medical Sciences, University of Aveiro, Aveiro, Portugal.
Université Paris Cité, CNRS, Inserm, Institut Cochin, Paris, France.
Gut Microbes. 2025 Dec;17(1):2542375. doi: 10.1080/19490976.2025.2542375. Epub 2025 Aug 6.
Laboratory-raised mice live approximately seven times longer and healthier lives compared to their wild counterparts, due to a standardized healthy diet and limited exposure to environmental stressors. Aging is associated with increased inflammation and microbial dysbiosis. Collectively, these influence microbiota evolution and may contribute to the enrichment in pathobiont frequency observed in old age. Alternatively, this increase could stem from a decline in colonization resistance, creating favorable conditions for pathobiont invasion. Here, we sought to test whether aging in healthy, controlled conditions, could prevent the selection of age-associated pathobionts. We have followed the adaptive evolution of a commensal strain of in the guts of mice of advanced age and found that it acquired several mutations common to bacteria colonizing young mice, which were absent in old animals. This, together with the increase in in mice of advanced age, suggest healthy aging. However, mutations acquired exclusively in the older were mainly pathoadaptive, tuning the metabolism to oxygen and iron availability, hypermotility, and biofilm formation.
与野生小鼠相比，实验室饲养的小鼠寿命延长约7倍，生活更健康，这归因于标准化的健康饮食和有限的环境应激源暴露。衰老与炎症增加和微生物群落失调有关。总体而言，这些因素影响微生物群的进化，并可能导致老年时致病共生菌频率的增加。或者，这种增加可能源于定植抗性的下降，为致病共生菌的入侵创造了有利条件。在这里，我们试图测试在健康、可控的条件下衰老是否能阻止与年龄相关的致病共生菌的选择。我们追踪了老年小鼠肠道中一种共生菌株的适应性进化，发现它获得了一些在年轻小鼠定植细菌中常见但老年动物中不存在的突变。这一点，再加上老年小鼠中[具体物质]的增加，表明是健康衰老。然而，仅在老年小鼠中获得的突变主要是致病适应性的，调整了对氧气和铁可用性的代谢、过度运动和生物膜形成。
