Gerobiotics: probiotics targeting fundamental aging processes

Abstract

Aging is recognized as a common risk factor for many chronic diseases and functional decline. The newly emerging field of geroscience is an interdisciplinary field that aims to understand the molecular and cellular mechanisms of aging. Several fundamental biological processes have been proposed as hallmarks of aging. The proposition of the geroscience hypothesis is that targeting holistically these highly integrated hallmarks could be an effective approach to preventing the pathogenesis of age-related diseases jointly, thereby improving the health span of most individuals. There is a growing awareness concerning the benefits of the prophylactic use of probiotics in maintaining health and improving quality of life in the elderly population. In view of the rapid progress in geroscience research, a new emphasis on geroscience-based probiotics is in high demand, and such probiotics require extensive preclinical and clinical research to support their functional efficacy. Here we propose a new term, “gerobiotics”, to define those probiotic strains and their derived postbiotics and para-probiotics that are able to beneficially attenuate the fundamental mechanisms of aging, reduce physiological aging processes, and thereby expand the health span of the host. We provide a thorough discussion of why the coining of a new term is warranted instead of just referring to these probiotics as anti-aging probiotics or with other similar terms. In this review, we highlight the needs and importance of the new field of gerobiotics, past and currently on-going research and development in the field, biomarkers for potential targets, and recommended steps for the development of gerobiotic products. Use of gerobiotics could be a promising intervention strategy to improve health span and longevity of humans in the future.

Nicotinamide Phosphoribosyltransferase as a Key Molecule of the Aging/Senescence Process

“…It is known that gut microbiome composition can differ between aging individuals that are of different health status [ 74 ]. Therefore, information on the gerobiotic status (composition of probiotic and parabiotic strains that are able to impact fundamental mechanisms of aging; reviewed by Tsai et al [ 75 ]) of aging individuals undergoing NAD + supplementation should be monitored through the course of treatment to ensure that accurate conclusions of the treatment outcome are made.…”

Effects of anti-aging interventions on intestinal microbiota

“…Some clinical studies have even proven the potential of some probiotics for the treatment of diseases such as intestinal diseases, metabolic diseases and neurological diseases. 127 , 128 For example, probiotic intervention may reduce the risk of antibiotic-associated diarrhea by 51% with no apparent increase in the risk of side effects. 129 Bifidobacterium breve B-3 has potential as a functional food ingredient to reduce body fat in healthy preobese individuals.…”

Novel Insights into the Role of Probiotics in Respiratory Infections, Allergies, Cancer, and Neurological Abnormalities

“…Nowadays, the changes of Homo sapiens microbiota are expected to exert an ultimate impact on aging advancement [ 133 ]. It is speculated that probiotics can blunt the progression of aging processes through the possible factors that govern age-related changes of the gut microbiome, age-related hallmarks (e.g., mitochondria dysfunction, telomere attrition), impact the severity and progression of cellular senescence, oxidative stress, epigenetic alteration, alteration of intracellular and intercellular communication, deprivation of proteostasis and including others [ 133 , 134 , 135 ].…”

“…Nowadays, the changes of Homo sapiens microbiota are expected to exert an ultimate impact on aging advancement [ 133 ]. It is speculated that probiotics can blunt the progression of aging processes through the possible factors that govern age-related changes of the gut microbiome, age-related hallmarks (e.g., mitochondria dysfunction, telomere attrition), impact the severity and progression of cellular senescence, oxidative stress, epigenetic alteration, alteration of intracellular and intercellular communication, deprivation of proteostasis and including others [ 133 , 134 , 135 ]. For example, Kumar and co-workers recently reported the anti-senescence potential of secretory metabolites of L. fermentum that mitigated the formation and severity of stress-induced senescence by a mechanism that relied on the downregulated phosphorylation of the PI3K–Akt–mTOR pathway and modulated the senescence-associated biomarkers such as p21WAF1, p38MAPK, p53, SA-β-gal, iNOS, COX-2, NF-κB and DNA damage response in 3T3-L1 preadipocytes [ 136 ].…”

“…At the moment, testing probiotic bacteria for longevity advancement in humans is not reliable due to comprehensive and complex study design, which would require decades of years for investigations, data analysis, and reproducibility to wrap up at least a definitive small-scale conclusion. Recently, a group of researchers defined probiotics that can prolong the health span of the host as “gerobiotics” [ 133 ]. The use of probiotics to attenuate the mechanisms of aging and minimize physiological aging processes is a new concept of major importance but will require decades of years to unveil.…”