Geroprotective potential of microbiome modulators in the Caenorhabditis elegans model

Abstract

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.

Keywords: Aging; C. elegans; Geroscience; Gut; Microbiome; Postbiotics; Probiotics.

Fig. 1

Supplementing probiotics and postbiotics to C. elegans significantly improves lifespan by targeting multiple pathways. These include the DAF (insulin-like), p38 MAPK, TLR/TIR, TGF-β-like, and JNK pathways, which modulate the innate immune system, activate stress responses, and change feeding patterns and host metabolism. AMPs, antimicrobial peptides; C. elegans, Caenorhabditis elegans; DAF, dauer formation; JNK, c-Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; TGF-β, transforming growth factor-β; TIR, Toll-interleukin repeat; TLR, Toll-like receptor