Gut microbiome pattern reflects healthy ageing and predicts survival in humans

Wilmanski, Tomasz; Diener, Christian; Rappaport, Noa; Patwardhan, Sushmita; Wiedrick, Jack; Lapidus, Jodi; Earls, John C.; Zimmer, Anat; Glusman, Gustavo; Robinson, Max; Yurkovich, James T.; Kado, Deborah M.; Cauley, Jane A.; Zmuda, Joseph M.; Lane, Nancy E.; Magis, Andrew T.; Lovejoy, Jennifer C.; Hood, Leroy; Gibbons, Sean M.; Orwoll, Eric S.; Price, Nathan D.

doi:10.1038/s42255-021-00348-0

Cited by 374 publications

(383 citation statements)

References 63 publications

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“…In particular, only healthy aging mice showed significantly increased Shannon diversity with age. Consistent with previous work 68 , our study also linked aging to an increase in interindividual variation in gut microbial community composition, with interindividual variation being especially high in the normal aging group. This suggested that the unhealthy aging related changes in the gut microbiota are likely stochastic, leading to community instability.…”

Section: ∆ F Isupporting

confidence: 91%

Gut Microbiota predicts Healthy Late-life Aging in Male Mice

Mitchell

MacArthur

et al. 2021

Preprint

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Calorie restriction (CR) extends lifespan and retards age-related chronic diseases in most species. There is growing evidence that the gut microbiota has a pivotal role in host health and age-related pathological conditions. Yet, it is still unclear how CR and the gut microbiota are related to healthy aging. Here we report findings from a small longitudinal study of male C57BL/6 mice maintained on either ad libitum or mild (15%) CR diets from 21 months of age and tracked until natural death. We demonstrate that CR results in a significant reduction in frailty index (FI), a well-established indicator of aging. We observed significant alterations in bacterial load, diversity, and compositional patterns of the mouse gut microbiota during the aging process. Interrogating the FI-related microbial features using machine learning techniques, we show that gut microbial signatures from 21-month-old mice can predict the healthy aging of 30-month-old mice with reasonable accuracy. This study deepens our understanding of the links between CR, gut microbiota, and frailty in the aging process of mice.

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Section: ∆ F Isupporting

confidence: 91%

Gut Microbiota predicts Healthy Late-life Aging in Male Mice

Mitchell

MacArthur

et al. 2021

Preprint

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“…Given its developing importance to health and disease, the gut microbiota represents a new area in healthy ageing and longevity research. Wilmanski et al [89] have described the dynamics of the gut microbiota across human life course, in a detailed phenotyping of 9000 subjects spanning 18-101 years of age. This investigation has revealed that the gut microbiota tends to become more unique to respective individuals with increasing chronological age, and this 'uniqueness' was characterised by a distinct shift in plasma gut microbial metabolites, with significant changes in phenylalanine and tryptophan pathways.…”

Section: Of Microbiome and Menmentioning

confidence: 99%

A biomimetic natural sciences approach to understanding the mechanisms of ageing in burden of lifestyle diseases

et al. 2021

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The worldwide landscape of an ageing population and age-related disease brings with it huge socio-economic and public healthcare concerns across nations. Correspondingly, monumental human and financial resources have been invested in biomedical research, with a mission to decode the mechanisms of ageing and how these contribute to age-related disease. Multiple hallmarks of ageing have been identified that are common across taxa, highlighting their fundamental importance. These include dysregulated mitochondrial metabolism and telomeres biology, epigenetic modifications, cell–matrix interactions, proteostasis, dysregulated nutrient sensing, stem cell exhaustion, inflammageing and immuno-senescence. While our understanding of the molecular basis of ageing is improving, it remains a complex and multifactorial process that remains to be fully understood. A key aspect of the shortfall in our understanding of the ageing process lies in translating data from standard animal models to humans. Consequently, we suggest that a ‘biomimetic’ and comparative approach, integrating knowledge from species in the wild, as opposed to inbred genetically homogenous laboratory animals, can provide powerful insights into human ageing processes. Here we discuss some particularities and comparative patterns among several species from the animal kingdom, endowed with longevity or short lifespans and unique metabolic profiles that could be potentially exploited to the understanding of ageing and age-related diseases. Based upon lessons from nature, we also highlight several avenues for renewed focus in the pathophysiology of ageing and age-related disease (i.e. diet-microbiome-health axis, oxidative protein damage, adaptive homoeostasis and planetary health). We propose that a biomimetic alliance with collaborative research from different disciplines can improve our understanding of ageing and age-related diseases with long-term sustainable utility.

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“…There is enough evidence available to suggest a correlation between gut dysbiosis, longevity and the prevalence of chronic disorders (Cardenas et al, 2014;Kamo et al, 2017;Lee et al, 2019). In fact, a recent report highlights that gut microbiome composition is a predictor of human survival and increased abundance of Bacteroides or low gut microbiome uniqueness is associated with decreased lifespan and enhanced morbidity (Wilmanski et al, 2021). Based on machine learning, another recent report inferred that age-related changes in the gut microflora can be used to precisely predict the age of an individual (Galkin et al, 2020).…”

Section: Gut Microbiota In Aging and Associated Diseasesmentioning

confidence: 99%

Gut Microbiome and Cellular Senescence in the Context of Aging and Disease: An Emerging Frontier

Sharma¹

2021

Preprint

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The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. 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 gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging 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 have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.

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Gut microbiome pattern reflects healthy ageing and predicts survival in humans

Cited by 374 publications

References 63 publications

Gut Microbiota predicts Healthy Late-life Aging in Male Mice

Gut Microbiota predicts Healthy Late-life Aging in Male Mice

A biomimetic natural sciences approach to understanding the mechanisms of ageing in burden of lifestyle diseases

Gut Microbiome and Cellular Senescence in the Context of Aging and Disease: An Emerging Frontier

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