衰老涉及机体功能的退化,导致多种病理的出现。环境刺激,包括生活方式,可以影响这一过程的轨迹,并可以用作追求健康衰老的工具。为了评估表观遗传机制在这种情况下的作用,我们已经生成了以丰富环境形式暴露于环境刺激的年轻和老年动物的雄性小鼠背侧海马体的块状组织和单细胞多组图。我们提出了衰老过程的分子图谱,突出显示两个不同的轴,与炎症和mRNA代谢失调有关,在功能性RNA和蛋白质水平。此外,我们报道了异染色质结构域的改变,包括二价染色质的损失和发现异染色质开关现象,从而通过兼性异染色质的增加部分减轻了组成性异染色质的损失。值得注意的是,我们观察到在环境富集的背景下,大量与衰老相关的改变的多维逆转,特别与神经胶质和少突胶质细胞途径有关。总之,我们的工作描述了衰老背景下环境刺激的表观基因组景观,并揭示了生活方式干预如何导致衰老相关衰退的多层逆转.
Aging involves the deterioration of organismal function, leading to the emergence of multiple pathologies. Environmental stimuli, including lifestyle, can influence the trajectory of this process and may be used as tools in the pursuit of healthy aging. To evaluate the role of epigenetic mechanisms in this context, we have generated bulk tissue and single cell multi-omic maps of the male mouse dorsal hippocampus in young and old animals exposed to environmental stimulation in the form of enriched environments. We present a molecular atlas of the aging process, highlighting two distinct axes, related to inflammation and to the dysregulation of mRNA metabolism, at the functional RNA and protein level. Additionally, we report the alteration of
heterochromatin domains, including the loss of bivalent chromatin and the uncovering of a
heterochromatin-switch phenomenon whereby constitutive
heterochromatin loss is partially mitigated through gains in facultative
heterochromatin. Notably, we observed the multi-omic reversal of a great number of aging-associated alterations in the context of environmental enrichment, which was particularly linked to glial and oligodendrocyte pathways. In conclusion, our work describes the epigenomic landscape of environmental stimulation in the context of aging and reveals how lifestyle intervention can lead to the multi-layered reversal of aging-associated decline.