USF Center for Microbiome Research, Microbiomes Institute, University of South Florida, 12901 Bruce B Downs Blvd, MDC 78, Tampa, FL, 33612, USA.
Department of Neurosurgery and Brain Repair, University of South Florida, Tampa, FL, USA.
Geroscience. 2024 Feb;46(1):129-151. doi: 10.1007/s11357-023-00901-7. Epub 2023 Aug 10.
Aging is associated with cellular and physiological changes, which significantly reduce the quality of life and increase the risk for disease. Geroprotectors improve lifespan and slow the progression of detrimental aging-related changes such as immune system senescence, mitochondrial dysfunction, and dysregulated nutrient sensing and metabolism. Emerging evidence suggests that gut microbiota dysbiosis is a hallmark of aging-related diseases and microbiome modulators, such as probiotics (live bacteria) or postbiotics (non-viable bacteria/bacterial byproducts) may be promising geroprotectors. However, because they are strain-specific, the geroprotective effects of probiotics and postbiotics remain poorly understood and understudied. Drosophila melanogaster, Caenorhabditis elegans, and rodents are well-validated preclinical models for studying lifespan and the role of probiotics and/or postbiotics, but each have their limitations, including cost and their translation to human aging biology. C. elegans is an excellent model for large-scale screening to determine the geroprotective potential of drugs or probiotics/postbiotics due to its short lifecycle, easy maintenance, low cost, and homology to humans. The purpose of this article is to review the geroprotective effects of microbiome modulators and their future scope, using C. elegans as a model. The proposed geroprotective mechanisms of these probiotics and postbiotics include delaying immune system senescence, preventing or reducing mitochondrial dysfunction, and regulating food intake (dietary restriction) and metabolism. More studies are warranted to understand the geroprotective potential of probiotics and postbiotics, as well as other microbiome modulators, like prebiotics and fermented foods, and use them to develop effective therapeutics to extend lifespan and reduce the risk of debilitating aging-related diseases.
衰老是与细胞和生理变化相关的,这些变化显著降低了生活质量并增加了患病风险。衰老保护剂可延长寿命并减缓与衰老相关的有害变化的进展,如免疫系统衰老、线粒体功能障碍以及营养感知和代谢失调。新出现的证据表明,肠道微生物失调是与衰老相关疾病的标志,而微生物组调节剂,如益生菌(活细菌)或后生元(非存活细菌/细菌副产物),可能是有前途的衰老保护剂。然而,由于它们是菌株特异性的,益生菌和后生元的衰老保护作用仍知之甚少且研究不足。黑腹果蝇、秀丽隐杆线虫和啮齿动物是研究寿命以及益生菌和/或后生元作用的经过充分验证的临床前模型,但它们各自都有其局限性,包括成本和对人类衰老生物学的转化。秀丽隐杆线虫由于其生命周期短、易于维护、成本低且与人同源,是用于大规模筛选以确定药物或益生菌/后生元的衰老保护潜力的极佳模型。本文旨在通过秀丽隐杆线虫作为模型,综述微生物组调节剂的衰老保护作用及其未来前景。这些益生菌和后生元的拟议衰老保护机制包括延缓免疫系统衰老、预防或减少线粒体功能障碍以及调节食物摄入(饮食限制)和代谢。需要更多的研究来了解益生菌和后生元以及其他微生物组调节剂(如益生元和发酵食品)的衰老保护潜力,并利用它们开发有效的治疗方法来延长寿命并降低与衰老相关的衰弱性疾病的风险。