Department of Systems Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
Geroscience. 2024 Apr;46(2):1627-1639. doi: 10.1007/s11357-023-00915-1. Epub 2023 Sep 12.
Understanding the mechanisms of geroprotective interventions is central to aging research. We compare four prominent interventions: senolysis, caloric restriction, in vivo partial reprogramming, and heterochronic parabiosis. Using published mice transcriptomic data, we juxtapose these interventions against normal aging. We find a gene expression program common to all four interventions, in which inflammation is reduced and several metabolic processes, especially fatty acid metabolism, are increased. Normal aging exhibits the inverse of this signature across multiple organs and tissues. A similar inverse signature arises in three chronic inflammation disease models in a non-aging context, suggesting that the shift in metabolism occurs downstream of inflammation. Chronic inflammation is also shown to accelerate transcriptomic age. We conclude that a core mechanism of geroprotective interventions acts through the reduction of inflammation with downstream effects that restore fatty acid metabolism. This supports the notion of directly targeting genes associated with these pathways to mitigate age-related deterioration.
理解抗衰老干预措施的机制是衰老研究的核心。我们比较了四种突出的干预措施：衰老细胞清除、热量限制、体内部分重编程和异体共生。利用已发表的小鼠转录组数据，我们将这些干预措施与正常衰老进行对比。我们发现这四种干预措施都有一个共同的基因表达程序，其中炎症减少，几种代谢过程，特别是脂肪酸代谢增加。在多个器官和组织中，正常衰老表现出相反的特征。在非衰老的情况下，三种慢性炎症疾病模型中也出现了类似的反转特征，这表明代谢的转变发生在炎症的下游。慢性炎症也被证明会加速转录组年龄的增长。我们的结论是，抗衰老干预措施的核心机制是通过减少炎症来发挥作用，其下游效应可以恢复脂肪酸代谢。这支持了直接针对与这些途径相关的基因来减轻与年龄相关的恶化的观点。
