Aging/Longevity and the Microbiome
The role of the gut microbiome in the aging process. Slowing aging via gut microbiome restoration techniques like Fecal Microbiota Transplants (FMT).
Summary:
Dysbiosis increases with age, is associated with all the diseases of old age, and seems to play a crucial role in aging itself. FMT from young donors is likely to have anti-aging effects by restoring eubiosis and reducing inflammation.
Reviews:
Review, 2024: Fecal Microbiota Transplantation, a tool to transfer healthy longevity https://www.sciencedirect.com/science/article/pii/S1568163724004033
Review, 2022: A gut-centric view of aging: Do intestinal epithelial cells contribute to age-associated microbiota changes, inflammaging, and immunosenescence? https://onlinelibrary.wiley.com/doi/10.1111/acel.13700
Review, 2018: The role of the gut microbiome during host ageing https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6051225/ "Recent work in model organisms has revealed for the first time that gut microbes can modulate ageing, opening new questions and opportunities to uncover novel ageing-modulating mechanisms and to design anti-ageing interventions by targeting the gut microbiota"
Review, 2018: The Gut Microbiota and Healthy Aging: A Mini-Review https://www.karger.com/Article/FullText/490615
Review, 2017: Gut Microbiota Contribute to Age-Related Changes in Skeletal Muscle Size, Composition, and Function: Biological Basis for a Gut-Muscle Axis: https://link.springer.com/article/10.1007/s00223-017-0345-5
Review, 2017: Gut microbiota changes in the extreme decades of human life: a focus on centenarians: https://link.springer.com/article/10.1007/s00018-017-2674-y
Review, 2017: Gut microbiota: A player in aging and a target for anti-aging intervention.
Review, 2017: The genetics of human longevity: an intricacy of genes, environment, culture and microbiome.
Review, 2016: Gut Microbiota and Extreme Longevity.
Review, 2016: Gut Instincts: microbiota as a key regulator of brain development, ageing and neurodegeneration.
Review, 2016: Gender, aging and longevity in humans: an update of an intriguing/neglected scenario paving the way to a gender-specific medicine.
Review, 2016: Anti-Aging Effects of Probiotics.
Review, 2016: Gut Bifidobacteria Populations in Human Health and Aging: https://journal.frontiersin.org/article/10.3389/fmicb.2016.01204/full
General:
Gut bacterial metabolite promotes neural cell death leading to cognitive decline (Jun 2022, mice and elderly people) https://medicalxpress.com/news/2022-06-gut-bacterial-metabolite-neural-cell.html Gut bacterial isoamylamine promotes age-related cognitive dysfunction by promoting microglial cell death.
Functional microbiome deficits associated with ageing: Chronological age threshold (Nov 2019, n=83) https://onlinelibrary.wiley.com/doi/10.1111/acel.13063 "synthesis of proteins involved in tryptophan and indole production and the faecal concentrations of these metabolites are directly correlated and progressively decrease with age. An age threshold for a 50% decrease is observed ca. 11–31 years old, and a greater than 90% reduction is observed from the ages of 34–54 years"
Suppression of the gut microbiome ameliorates age-related arterial dysfunction and oxidative stress in mice (Feb 2019): https://doi.org/10.1113/JP277336
Age-associated Impairment of the Mucus Barrier Function is Associated with Profound Changes in Microbiota and Immunity (2019): https://www.nature.com/articles/s41598-018-35228-3 "The physiological and immunological changes we observed in the intestine in old age, could have major consequences beyond the gut."
Mid-life microbiota crises: middle age is associated with pervasive neuroimmune alterations that are reversed by targeting the gut microbiome (May 2019, mice): https://www.nature.com/articles/s41380-019-0425-1
Age-related Alterations in Microbiota-Gut-Brain Axis (2017): https://www.sciencedirect.com/science/article/pii/S088915911730034X "These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioral, affective and cognitive functions seen in aging."
An Investigation Into Physical Frailty as a Link Between the Gut Microbiome and Cognitive Health (Dec 2018) https://www.frontiersin.org/articles/10.3389/fnagi.2018.00398/full "first human study that links cognitive performance to gut microbiome in ageing adults. Highlights importance of role of physical frailty when investigating cognitive performance"
Greater Microbial Translocation & Vulnerability to Metabolic Disease in Healthy Aged Female Monkeys. (2018): https://www.nature.com/articles/s41598-018-29473-9 Ageing may lead to lower control over colonization at the mucosal surface, & reduced clearance of pathogens resulting in microbial translocation & inflammation.
We provide novel evidence that microbiota may control intestinal epithelial stem cell (IESC) proliferation in part through microRNAs (miRNAs) (2017): https://www.jbc.org/content/early/2017/01/04/jbc.M116.770099.long. Review on gut microbiota & intestinal stem cells(2017): https://journal.frontiersin.org/article/10.3389/fimmu.2017.00599/full
Microbiome and Longevity: Gut Microbes Send Signals to Host Mitochondria (2017): https://www.sciencedirect.com/science/article/pii/S0092867417306414. Related article: Gut Bacteria May Help Slow Down Process of Ageing.
A Tiny Tweak to Gut Bacteria Can Extend an Animal’s Life (2017): https://www.theatlantic.com/science/archive/2017/06/a-tiny-tweak-to-gut-bacteria-can-extend-an-animals-life/530364
Chemical Compound That Gives Poop Its Stink Extends Healthy Lifespan in Animals: https://gizmodo.com/chemical-compound-that-gives-poop-its-stink-extends-hea-1798156486
Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians (Jul 2021) https://www.nature.com/articles/s41586-021-03832-5
Age prediction:
Human Skin, Oral, and Gut Microbiomes Predict Chronological Age (Feb 2020) https://www.gutmicrobiotaforhealth.com/the-skin-microbiome-is-more-predictive-of-age-than-the-gut-microbiome/ "the skin microbiome provides the best prediction of age. In total, this represents the most comprehensive investigation of microbiome and age, with 8,959 samples from 10 studies"
Researchers studying the gut bacteria of thousands of people around the globe have come to one conclusion: The microbiome is a surprisingly accurate biological clock, able to predict the age of most people within years https://www.sciencemag.org/news/2019/01/bacteria-your-gut-may-reveal-your-true-age - Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects (2018): https://doi.org/10.1101/507780
FMT:
Review, May 2023: Fecal microbiota transplantation holds the secret to youth https://www.sciencedirect.com/science/article/abs/pii/S0047637423000490
FMT from young and old:
Fecal microbiota transplanted from old mice promotes more colonic inflammation, proliferation, and tumor formation in azoxymethane-treated A/J mice than microbiota originating from young mice (Nov 2023) https://www.tandfonline.com/doi/full/10.1080/19490976.2023.2288187 "These findings support an etiological role for altered gut microbial communities in the increased risk for CRC with increasing age and establishes that such risk can be transmitted between individuals"
Gut microbiota dysbiosis promotes age-related atrial fibrillation by lipopolysaccharide and glucose-induced activation of NLRP3-inflammasome (Mar 2021) https://academic.oup.com/cardiovascres/advance-article-abstract/doi/10.1093/cvr/cvab114/6184135 "Herein, by using a fecal microbiota transplantation (FMT) rat model, we demonstrated that the high AF susceptibility of aged rats could be transmitted to a young host. Finally, aged rats colonized with youthful microbiota restored intestinal structure and atrial NLRP3-inflammasome activity, which suppressed the development of aged-related AF."
Young versus aged microbiota transplants to germ-free mice: increased short-chain fatty acids and improved cognitive performance (Sep 2020) https://www.tandfonline.com/doi/full/10.1080/19490976.2020.1814107 "We conclude that an aged microbiome alone is sufficient to decrease SCFAs in the host and to produce cognitive decline"
FMT from young to old:
The brain-protective mechanism of fecal microbiota transplantation from young donor mice in the natural aging process via exosome, gut microbiota, and metabolomics analyses (Jul 2024) https://forum.humanmicrobiome.info/threads/the-brain-protective-mechanism-of-fecal-microbiota-transplantation-fro.508/
Fecal Microbiota Transfer from Young Mice Reverts Vascular Aging Hallmarks and Metabolic Impairments in Aged Mice (Jul 2024) https://forum.humanmicrobiome.info/threads/fecal-microbiota-transfer-from-young-mice-reverts-vascular-aging-hallm.494/
Rejuvenating fecal microbiota transplant enhances peripheral nerve repair in aged mice by modulating endoneurial inflammation (Apr 2024) https://www.sciencedirect.com/science/article/abs/pii/S0014488624001006
Fecal Microbiota Transplantation Attenuates Frailty via Gut-Muscle Axis in Old Mice (Apr 2024) https://www.aginganddisease.org/EN/10.14336/AD.2024.0321
Preliminary evidence for developing safe and efficient fecal microbiota transplantation as potential treatment for aged related cognitive impairments (Apr 2023, n=5) https://www.frontiersin.org/articles/10.3389/fcimb.2023.1103189/full "FMT maintained and improved cognitive function in mild cognitive impairment by changing gut microbiota structure"
Faecal microbiota transplantation from young rats attenuates age-related sarcopenia revealed by multiomics analysis (July 2023) https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13294
Fecal microbiota transplantation from young mice rejuvenates aged hematopoietic stem cells by suppressing inflammation (Jan 2023) https://ashpublications.org/blood/article-abstract/doi/10.1182/blood.2022017514/494137/Fecal-microbiota-transplantation-from-young-mice
Gut microbiota of the young ameliorates physical fitness of the aged in mice (Dec 2022) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01386-w "young-derived gut microbiota rejuvenates the physical fitness of the aged by altering the microbial composition of the gut and gene expression in muscle and skin"
Regular fecal microbiota transplantation to Senescence Accelerated Mouse-Prone 8 (SAMP8) mice delayed the aging of locomotor and exploration ability by rejuvenating the gut microbiota (Oct 2022) https://www.frontiersin.org/articles/10.3389/fnagi.2022.991157/full "FMT from younger donors can delay aging-related declines in locomotor and exploration ability in mice"
Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (Apr 2022) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-022-01243-w
Fecal microbiota transplantation from young donor mice improves ovarian function in aged mice (May 2022) https://www.sciencedirect.com/science/article/pii/S1673852722001576 "These results suggest that FMT from young donors could be a good choice for delaying ovarian aging"
Microbiota from young mice counteracts selective age-associated behavioral deficits (Aug 2021, mice) https://www.newswise.com/articles/microbes-turn-back-the-clock-as-research-discovers-their-potential-to-reverse-aging-in-the-brain - https://www.nature.com/articles/s43587-021-00093-9 Microbes Turn Back the Clock as Research Discovers Their Potential to Reverse Aging in the Brain.
Study suggests age-related immune system decline is not irreversible. Fecal transplants from young mice to old mice resulted in significant improvements to the animal's gut immune system. Heterochronic faecal transplantation boosts gut germinal centres in aged mice (Jun 2019) https://newatlas.com/gut-bacteria-microbiome-aging-immune-system/59979/
‘Young poo’ makes aged fish live (40%) longer. The gut microbes of young killifish can extend the lifespans of older fish – hinting at the microbiome’s role in aging (2017): https://www.nature.com/news/young-poo-makes-aged-fish-live-longer-1.21770
Young fecal transplantation mitigates the toxicity of perfluorobutanesulfonate and potently refreshes the reproductive endocrine system in aged recipients (Jul 2022, zebrafish) https://www.sciencedirect.com/science/article/pii/S0160412022003452
FMT from old to young:
Aged Gut Microbiome Induces Metabolic Impairment and Hallmarks of Vascular and Intestinal Aging in Young Mice (Oct 2024) https://www.mdpi.com/2076-3921/13/10/1250
"pre-pregnancy colonization of young dams with microbiome from aged female donors significantly increased fetal loss. Offspring displayed persistent depressive and anxiety-like phenotypes" https://forum.humanmicrobiome.info/threads/maternal-dysbiosis-produces-long-lasting-behavioral-changes-in-offspri.667/ Maternal dysbiosis produces long-lasting behavioral changes in offspring (Oct 2024, mice).
Age-related gut microbiota transplantation disrupts myocardial energy homeostasis and induces oxidative damage (Feb 2024, mice) https://www.sciencedirect.com/science/article/abs/pii/S002231662400097X "an aged microbiota can modulate metabolism and induce cardiac injury"
Fecal microbiota transplant from aged donor mice affects spatial learning and memory via modulating hippocampal synaptic plasticity- and neurotransmission-related proteins in young recipients (Oct 2020) "In short, the young mice began to behave like older mice, in terms of their cognitive function" https://medicalxpress.com/news/2020-10-poo-transplant-day-secret-eternal.html
Age-associated gut microbiota impairs hippocampus-dependent memory in a vagus-dependent manner (Jun 2022, mice, and human-to-mouse FMT) https://insight.jci.org/articles/view/147700
FMT from elderly people and aged mice caused significantly more severe cognitive impairment in transplanted young mice than those from young adults and mice. Severing the vagus nerve significantly inhibited the occurrence of cognitive impairment. Two bacteria species also singled out (Jul 2020) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-020-00881-2 The extracellular vesicle of gut microbial Paenalcaligenes hominis is a risk factor for vagus nerve-mediated cognitive impairment.
FMT from aged donors impairs cardiac function and physical activity, induces metabolic alterations, leading to body weight gain, impaired glucose tolerance, increased respiratory exchange ratio (RER), and enhanced fat accumulation in mice with heart failure. https://www.sciencedirect.com/science/article/abs/pii/S0925443924002606 Aged microbiota exacerbates cardiac failure by PPARα/PGC1α pathway (May 2024)
Age-related shifts in gut microbiota contribute to cognitive decline in aged rats (May 2020) https://www.aging-us.com/article/103093/text "FMT from aged to young rats. This study provides direct evidence for the contribution of gut microbiota to the cognitive decline during normal aging and suggests that restoring microbiota homeostasis in the elderly may improve cognitive function"
Gut microbes from aged mice induce inflammation in young mice (May 2024) https://news.illinois.edu/view/6367/1013133501 Aging amplifies a gut microbiota immunogenic signature linked to heightened inflammation.
Faecal microbiota transplant from aged donor mice into young recipients affects spatial learning and memory (Dec 2019, mice) https://www.biorxiv.org/content/10.1101/866459v1 "FMT from aged donors led to impaired spatial learning and memory in adult recipients; modulated the expression of a variety of proteins implicated in maintenance of synaptic plasticity and neurotransmission in the hippocampus of adult recipients. Microglia cells of the hippocampus fimbria acquired an ageing-like phenotype. We conclude that the age-associated alteration of the gut microbiota contributes to the decline of key functions of the CNS through the modulation of hippocampal synaptic plasticity-related proteins."
Age‐related changes in the gut microbiota influence systemic inflammation and stroke outcome (May 2018). https://doi.org/10.1002/ana.25250 Aged biome increased the levels of systemic proinflammatory cytokines. We conclude that the gut microbiota can be modified to positively impact outcomes from age‐related diseases.
Gut bacteria from old mice induce age-related chronic inflammation when transplanted into young mice (2017): https://www.eurekalert.org/pub_releases/2017-11/f-nlf103117.php
Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction (2017): https://www.the-scientist.com/?articles.view/articleNo/49189/title/Gut-Microbes-Contribute-to-Age-Associated-Inflammation-in-Mice "These data suggest that aging-associated microbiota promote inflammation and that reversing these age-related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity."
Microbial signatures:
Distinct intestinal microbial signatures linked to accelerated systemic and intestinal biological aging (Feb 2024) https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-024-01758-4
Toward an improved definition of a healthy microbiome for healthy aging (Nov 2022) https://www.nature.com/articles/s43587-022-00306-9 "increasing uniqueness and diversity are features of an aging–host microbiome in general (especially for the Westernized populations), but not necessarily a signature of a putatively beneficial microbiome" https://archive.ph/Fw7NF#selection-2693.12-2697.0
Gut microbiome pattern reflects healthy ageing and predicts survival in humans (Feb 2021, n>9000) https://www.nature.com/articles/s42255-021-00348-0
Comparative analysis of the gut microbiota in centenarians and young adults shows a common signature across genotypically non-related populations (Feb 2019): https://www.sciencedirect.com/science/article/pii/S0047637418302057 "Akkermansia, Alistipes, and Ruminococcoaceae D16 as signature taxa of longevity"
Age-Associated Changes in Gut Microbiota and Dietary Components Related with the Immune System in Adulthood and Old Age: A Cross-Sectional Study (July 2019) https://www.mdpi.com/2072-6643/11/8/1765/htm
Biological Aging and the Human Gut Microbiota (2017) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5861892/ "Increasing biological age in community-dwelling adults is associated with gastrointestinal dysbiosis"
Study Links Gut Microbiome With "Ridiculously Healthy" Aging (2017): https://www.psychologytoday.com/blog/the-athletes-way/201710/study-links-gut-microbiome-ridiculously-healthy-aging "the gut microbiota of persons in their 20s was distinct from those of other age cohorts. The major differences between groups in the gut microbiota profiles were found before age 20". The Gut Microbiota of Healthy Aged Chinese Is Similar to That of the Healthy Young.
Gut Microbiota and Extreme Longevity: we provide for the first time the phylogenetic microbiota analysis of semi-supercentenarians, i.e., 105–109 years old, in comparison to adults, elderly, and centenarians (2016): https://www.sciencedirect.com/science/article/pii/S0960982216303384
Gut microbiota signatures of longevity. We compare the gut microbiota of Chinese long-living people with younger age groups, and with the results from the Italian population, to identify gut-microbial signatures of healthy aging (2016): https://www.cell.com/current-biology/fulltext/S0960-9822(16)30927-7
Diversity:
Human gut microbiome viewed across age and geography (2012) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376388/ "bacterial diversity increased with age"
Bacterial diversity was increased with age (2018): https://doi.org/10.1371/journal.pone.0209209 Different host factors are associated with patterns in bacterial and fungal gut microbiota in Slovenian healthy cohort.
Diversity, compositional and functional differences between gut microbiota of children and adults (Jan 2020) https://www.nature.com/articles/s41598-020-57734-z 2,111 children (9 to 12), 1427 adults (46 to 88). Children had significantly lower gut microbiome diversity.
Links between environment, diet, and the hunter-gatherer microbiome (2018): https://sci-hub.tw/https://doi.org/10.1080/19490976.2018.1494103 Mixed results from various studies on diversity & age. Seems to be dictated by lifestyle/environment.
Age and the aging process significantly alter the small bowel microbiome (Sep 2021) https://www.sciencedirect.com/science/article/pii/S2211124721012195 "Duodenal microbiome diversity decreases and coliforms increase in older subjects"
Peptides:
Antimicrobial peptides extend lifespan in Drosophila.
Eco-Aging: stem cells and microbes are controlled by aging antagonist FoxO. The review highlights the dual role that the conserved master regulator FoxO has in aging by coordinating both stem cell proliferation and antimicrobial peptides, effector molecules of the innate immune system.