Borrego-Ruiz Alejandro, Borrego Juan J
Departamento de Psicología Social y de las Organizaciones, Universidad Nacional de Educación a Distancia (UNED), 28040 Madrid, Spain.
Departamento de Microbiología, Universidad de Málaga, 29071 Málaga, Spain.
Genes (Basel). 2024 Dec 14;15(12):1599. doi: 10.3390/genes15121599.
BACKGROUND/OBJECTIVES: Aging is a natural physiological process involving biological and genetic pathways. Growing evidence suggests that alterations in the epigenome during aging result in transcriptional changes, which play a significant role in the onset of age-related diseases, including cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. For this reason, the epigenetic alterations in aging and age-related diseases have been reviewed, and the major extrinsic factors influencing these epigenetic alterations have been identified. In addition, the role of the gut microbiome and its metabolites as epigenetic modifiers has been addressed.
Long-term exposure to extrinsic factors such as air pollution, diet, drug use, environmental chemicals, microbial infections, physical activity, radiation, and stress provoke epigenetic changes in the host through several endocrine and immune pathways, potentially accelerating the aging process. Diverse studies have reported that the gut microbiome plays a critical role in regulating brain cell functions through DNA methylation and histone modifications. The interaction between genes and the gut microbiome serves as a source of adaptive variation, contributing to phenotypic plasticity. However, the molecular mechanisms and signaling pathways driving this process are still not fully understood.
Extrinsic factors are potential inducers of epigenetic alterations, which may have important implications for longevity. The gut microbiome serves as an epigenetic effector influencing host gene expression through histone and DNA modifications, while bidirectional interactions with the host and the underexplored roles of microbial metabolites and non-bacterial microorganisms such as fungi and viruses highlight the need for further research.
背景/目的：衰老是一个涉及生物学和遗传途径的自然生理过程。越来越多的证据表明，衰老过程中表观基因组的改变会导致转录变化，这在包括癌症、心血管疾病、糖尿病和神经退行性疾病在内的与年龄相关疾病的发病中起重要作用。因此，已对衰老及与年龄相关疾病中的表观遗传改变进行了综述，并确定了影响这些表观遗传改变的主要外在因素。此外，还探讨了肠道微生物群及其代谢产物作为表观遗传修饰因子的作用。
长期暴露于空气污染、饮食、药物使用、环境化学物质、微生物感染、体育活动、辐射和压力等外在因素会通过多种内分泌和免疫途径引发宿主的表观遗传变化，可能加速衰老过程。多项研究报告称，肠道微生物群通过DNA甲基化和组蛋白修饰在调节脑细胞功能中起关键作用。基因与肠道微生物群之间的相互作用是适应性变异的一个来源，有助于表型可塑性。然而，驱动这一过程的分子机制和信号通路仍未完全了解。
外在因素是表观遗传改变的潜在诱导因素，这可能对长寿具有重要意义。肠道微生物群作为一种表观遗传效应器，通过组蛋白和DNA修饰影响宿主基因表达，而与宿主的双向相互作用以及微生物代谢产物和真菌、病毒等非细菌微生物尚未充分探索的作用凸显了进一步研究的必要性。
