Emerging Interrelationship Between the Gut Microbiome and Cellular Senescence in the Context of Aging and Disease: Perspectives and Therapeutic Opportunities

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The significance of diversity, composition, and functional attributes of the gut microbiota in shaping human health is well recognized. Studies have shown that gut microbiota is closely linked to human aging, and changes in the gut microbiome can predict human survival and longevity. In addition, a causal relationship between gut microbiota dysbiosis and chronic age-related disorders is also becoming apparent. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between the gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the evolving relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis and diseases, have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship between the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity-promoting therapies.

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The Hallmarks of Aging

Carlos López-Otín, Maria Blasco, Linda Partridge … (2014)

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.

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Revised Estimates for the Number of Human and Bacteria Cells in the Body

Ron Sender, Shai Fuchs, Ron Milo (2016)

Reported values in the literature on the number of cells in the body differ by orders of magnitude and are very seldom supported by any measurements or calculations. Here, we integrate the most up-to-date information on the number of human and bacterial cells in the body. We estimate the total number of bacteria in the 70 kg "reference man" to be 3.8·1013. For human cells, we identify the dominant role of the hematopoietic lineage to the total count (≈90%) and revise past estimates to 3.0·1013 human cells. Our analysis also updates the widely-cited 10:1 ratio, showing that the number of bacteria in the body is actually of the same order as the number of human cells, and their total mass is about 0.2 kg.

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Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

Zeneng Wang, Elizabeth Klipfell, Brian J. Bennett … (2011)

Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely choline, trimethylamine N-oxide (TMAO), and betaine, were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted up-regulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and gut flora in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.

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Author and article information

Contributors

Rohit Sharma:

ORCID: http://orcid.org/0000-0001-6209-3845

rohit25sharma@gmail.com , rohit.sharma@shooliniuniversity.com

Journal

Journal ID (nlm-ta): Probiotics Antimicrob Proteins

Journal ID (iso-abbrev): Probiotics Antimicrob Proteins

Title: Probiotics and Antimicrobial Proteins

Publisher: Springer US (New York )

ISSN (Print): 1867-1306

ISSN (Electronic): 1867-1314

Publication date (Electronic): 5 January 2022

Pages: 1-16

Affiliations

GRID grid.430140.2, ISNI 0000 0004 1799 5083, Faculty of Applied Sciences & Biotechnology, , Shoolini University, ; Solan, 173229 India

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Rohit Sharma http://orcid.org/0000-0001-6209-3845

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Publisher ID: 9903

DOI: 10.1007/s12602-021-09903-3

PMC ID: 8728710

PubMed ID: 34985682

SO-VID: a592016c-1839-4952-bea1-4b521c4aa014

License:

This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

History

Date accepted : 28 December 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001409, Department of Science and Technology, Ministry of Science and Technology;

Emerging Interrelationship Between the Gut Microbiome and Cellular Senescence in the Context of Aging and Disease: Perspectives and Therapeutic Opportunities

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Most cited references 182

The Hallmarks of Aging

Revised Estimates for the Number of Human and Bacteria Cells in the Body

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease

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