scholarly journals THE GUT MICROBIOME AND AGING

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S833-S833
Author(s):  
Christy S Carter ◽  
Michal Masternak ◽  
Thomas W Buford
Keyword(s):  
Gut Microbiome ◽  
Multiple Organ ◽  
Model Systems ◽  
Multiple Model ◽  
Gut Dysbiosis ◽  
Critical Areas ◽  
Age Related ◽  
Organ Systems ◽  
Health And Disease ◽  
Gut Microorganisms

Abstract The human intestinal tract (i.e., “gut”) is inhabited by over 100 trillion microorganisms; including over 1000 species of known bacteria. These organisms have co-evolved with humans over millennia to live together for mutual benefit. Though long overlooked in considerations of human health and disease treatment, gut microorganisms are highly involved in numerous metabolic reactions which influence normal host physiology. A variety of biologic, medical, and lifestyle factors appear to contribute to gut dysbiosis in late-life, and interventions specifically designed to target these factors may be useful in restoring microbial balance. Evidence from both clinical and preclinical studies suggests that gut dysbiosis is related to age-related inflammation as well as age-related conditions including frailty, Alzheimer’s disease, and perhaps even longevity. Crosstalk between the gut and multiple organ systems (brain, heart, muscle etc.) may lead to the development of age-related diseases and loss of physiological function, although the signals are not well understood. In this symposium we address the broad topic of the Gut Microbiome and Aging by presenting evidence from multiple model systems (mice, rats and monkeys) and provide a forum to discuss critical areas of research for moving forward.

scholarly journals The Gut Microbiota and Healthy Aging: A Mini-Review

Gerontology ◽  
2018 ◽  
Vol 64 (6) ◽  
pp. 513-520 ◽  
Author(s):  
Sangkyu Kim ◽  
S. Michal Jazwinski
Keyword(s):  
Gut Microbiota ◽  
Individual Variation ◽  
Gut Microbiome ◽  
Chronological Age ◽  
Low Grade ◽  
Beneficial Effects ◽  
Gut Dysbiosis ◽  
Age Related ◽  
Host Health ◽  
Nutrient Signaling

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

scholarly journals Association Between Elevated suPAR, a New Biomarker of Inflammation, and Accelerated Aging

2020 ◽  
Author(s):  
Line Jee Hartmann Rasmussen ◽  
Avshalom Caspi ◽  
Antony Ambler ◽  
Andrea Danese ◽  
Maxwell Elliott ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Functional Decline ◽  
Accelerated Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Blood Levels ◽  
Urokinase Plasminogen Activator Receptor ◽  
Reactive Protein ◽  
Age Related ◽  
Organ Systems

Abstract Background To understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline. Methods We used data from the Dunedin Study, a population-representative 1972–1973 New Zealand birth cohort (n = 1037) that has observed participants to age 45 years. Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, C-reactive protein, and current health conditions. Results Of 997 still-living participants, 875 (88%) had plasma suPAR measured at age 45. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems, older facial appearance, and with structural signs of older brain age. Moreover, participants with higher suPAR levels had greater decline in physical function and cognitive function from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between ages 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years. Conclusions Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.

Diabesity: A Polygenic Model of Dietary-Induced Obesity from Ad Libitum Overfeeding of Sprague–Dawley Rats and Its Modulation by Moderate and Marked Dietary Restriction

2005 ◽  
Vol 33 (6) ◽  
pp. 650-674 ◽  
Author(s):  
Kevin P. Keenan ◽  
Chao-Min Hoe ◽  
Lori Mixson ◽  
Carol L. Mccoy ◽  
John B. Coleman ◽  
...  
Keyword(s):  
Body Fat ◽  
Dietary Restriction ◽  
Reproductive Organs ◽  
Multiple Organ ◽  
Sprague Dawley ◽  
Sd Rats ◽  
Age Related ◽  
Organ Systems ◽  
Estrous Cyclicity ◽  
Ad Libitum

This study compared the effects of ad libitum (AL) overfeeding and moderate or marked dietary restriction (DR) on the pathogenesis of a metabolic syndrome of diabesity comprised of age-related degenerative diseases and obesity in a outbred stock of Sprague–Dawley (SD) rats [Crl:CD (SD) IGS BR]. SD rats were fed Purina Certified Rodent Diet AL (group 1), DR at 72–79% of AL (group 2), DR at 68–72% of AL (group 3) or DR at 47–48% of AL (group 4) for 106 weeks. Interim necropsies were performed at 13, 26, and 53 weeks, after a 7-day 5-bromo-2-deoxyuridine (BrdU)-filled minipump implantation. Body weights, organ weights, carcass analysis, in-life data including estrous cyclicity, and histopathology were determined. At 6–7 weeks of age SD rats had 6% body fat. AL-feeding resulted in hypertriglyceridemia, hypercholesterolemia, and dietary-induced obesity (DIO) by study week 14, with 25% body fat that progressed to 36–42% body fat by 106 weeks. As early as 14 weeks, key biomarkers developed for spontaneous nephropathy, cardiomyopathy, and degenerative changes in multiple organ systems. Early endocrine disruption was indicated by changes in metabolic and endocrine profiles and the early development and progression of lesions in the pituitary, pancreatic islets, adrenals, thyroids, parathyroids, liver, kidneys, and other tissues. Reproductive senescence was seen by 9 months with declines in estrous cyclicity and pathological changes in the reproductive organs of both sexes fed AL or moderate DR, but not marked DR. The diabesity syndrome in AL-fed, DIO SD rats was readily modulated or prevented by moderate to marked DR. Moderate DR of balanced diets resulted in a better toxicology model by significantly improving survival, controlling adult body weight and obesity, reducing the onset, severity, and morbidity of age-related renal, endocrine, metabolic, and cardiac diseases. Moderate DR feeding reduces study-to-study variability, increases treatment exposure time, and increases the ability to distinguish true treatment effects from spontaneous aging. The structural and metabolic differences between the phenotypes of DIO and DR SD rats indicated changes of polygenic expression over time in this outbred stock. AL-overfeeding of SD rats produces a needed model of DIO and diabesity that needs further study of its patterns of polygenic expression and phenotype.

scholarly journals Counteracting age-related VEGF signaling insufficiency promotes healthy aging and extends life span

Science ◽  
2021 ◽  
Vol 373 (6554) ◽  
pp. eabc8479
Author(s):  
M. Grunewald ◽  
S. Kumar ◽  
H. Sharife ◽  
E. Volinsky ◽  
A. Gileles-Hillel ◽  
...  
Keyword(s):  
Life Span ◽  
Healthy Aging ◽  
Vascular Diseases ◽  
Tumor Burden ◽  
Multiple Organ ◽  
Vegf Signaling ◽  
Established Risk Factor ◽  
Age Related ◽  
Organ Systems ◽  
And Function

Aging is an established risk factor for vascular diseases, but vascular aging itself may contribute to the progressive deterioration of organ function. Here, we show in aged mice that vascular endothelial growth factor (VEGF) signaling insufficiency, which is caused by increased production of decoy receptors, may drive physiological aging across multiple organ systems. Increasing VEGF signaling prevented age-associated capillary loss, improved organ perfusion and function, and extended life span. Healthier aging was evidenced by favorable metabolism and body composition and amelioration of aging-associated pathologies including hepatic steatosis, sarcopenia, osteoporosis, “inflammaging” (age-related multiorgan chronic inflammation), and increased tumor burden. These results indicate that VEGF signaling insufficiency affects organ aging in mice and suggest that modulating this pathway may result in increased mammalian life span and improved overall health.

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

2021 ◽  
Author(s):  
Rohit Sharma
Keyword(s):  
Gut Microbiota ◽  
Cellular Senescence ◽  
Gut Microbiome ◽  
Biological Aging ◽  
Future Research ◽  
Age Related ◽  
Integrative View ◽  
Health And Disease ◽  
Molecular Aspects ◽  
Relationship Of

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.

scholarly journals Quantification of biological aging in young adults

2015 ◽  
Vol 112 (30) ◽  
pp. E4104-E4110 ◽  
Author(s):  
Daniel W. Belsky ◽  
Avshalom Caspi ◽  
Renate Houts ◽  
Harvey J. Cohen ◽  
David L. Corcoran ◽  
...  
Keyword(s):  
Young Adults ◽  
Brain Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Research Translation ◽  
Human Aging ◽  
Aging Research ◽  
Cross Sectional ◽  
Age Related ◽  
Organ Systems

Antiaging therapies show promise in model organism research. Translation to humans is needed to address the challenges of an aging global population. Interventions to slow human aging will need to be applied to still-young individuals. However, most human aging research examines older adults, many with chronic disease. As a result, little is known about aging in young humans. We studied aging in 954 young humans, the Dunedin Study birth cohort, tracking multiple biomarkers across three time points spanning their third and fourth decades of life. We developed and validated two methods by which aging can be measured in young adults, one cross-sectional and one longitudinal. Our longitudinal measure allows quantification of the pace of coordinated physiological deterioration across multiple organ systems (e.g., pulmonary, periodontal, cardiovascular, renal, hepatic, and immune function). We applied these methods to assess biological aging in young humans who had not yet developed age-related diseases. Young individuals of the same chronological age varied in their “biological aging” (declining integrity of multiple organ systems). Already, before midlife, individuals who were aging more rapidly were less physically able, showed cognitive decline and brain aging, self-reported worse health, and looked older. Measured biological aging in young adults can be used to identify causes of aging and evaluate rejuvenation therapies.

scholarly journals 15-PGDH as a Negative Regulator of Age-Related Organ Fitness

2020 ◽  
Author(s):  
Won Jin Ho ◽  
Julianne N.P. Smith ◽  
Young Soo Park ◽  
Matthew Hadiono ◽  
Kelsey Christo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tissue Injury ◽  
Peripheral Blood Cell ◽  
Multiple Organ ◽  
Negative Regulator ◽  
Post Transplantation ◽  
Aged Mice ◽  
Cell Counts ◽  
Age Related ◽  
Organ Systems

ABSTRACTEmerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cell regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ fitness of aged mice. Here we demonstrate that genetic loss of 15-PGDH (Hpgd) confers a protective effect on aging of murine hematopoietic and gastrointestinal (GI) tissues. Aged mice lacking 15-PGDH display increased hematopoietic output as assessed by peripheral blood cell counts, bone marrow and splenic stem cell compartments, and accelerated post-transplantation recovery compared to their WT counterparts. Loss of Hpgd expression also resulted in enhanced GI fitness and reduced local inflammation in response to colitis. Together these results suggest that 15-PGDH negatively regulates aged tissue regeneration, and that 15-PGDH inhibition may be a viable therapeutic strategy to ameliorate age-associated loss of organ fitness.ARTICLE SUMMARY15-PGDH as a Driver of Age-Related Tissue Dysfunction

scholarly journals Associations Between a New Biomarker of Elevated Chronic Inflammation and Accelerated Aging

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 141-142
Author(s):  
Line Rasmussen ◽  
Avshalom Caspi ◽  
Terrie Moffitt
Keyword(s):  
Chronic Inflammation ◽  
Functional Capacity ◽  
Functional Decline ◽  
Accelerated Aging ◽  
Multiple Organ ◽  
Biological Aging ◽  
Blood Levels ◽  
Urokinase Plasminogen Activator Receptor ◽  
Age Related ◽  
Organ Systems

Abstract To further understand and measure the association between chronic inflammation, aging, and age-related diseases, broadly applicable standard biomarkers of systemic chronic inflammation are needed. We tested whether elevated blood levels of the emerging chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR) were associated with accelerated aging, lower functional capacity, and cognitive decline. We used data from the population-representative longitudinal Dunedin Study (N=875). Plasma suPAR levels were analyzed at ages 38 and 45 years. We performed regression analyses adjusted for sex, smoking, and C-reactive protein. suPAR levels increased from 2.39 ng/mL (SD 0.89) at age 38 to 3.01 (SD 1.03) at age 45 years. Elevated suPAR was associated with accelerated pace of biological aging across multiple organ systems (β 0.28, 95% CI 0.21–0.35), older facial appearance (β 0.16, 95% CI 0.10–0.22), and with structural signs of older brain age (β 0.06, 95% CI -0.00–0.13). Moreover, participants with higher suPAR levels had lower functional capacity (more physical limitations [β 0.24, 95% CI 0.18–0.30]; slower gait speed [β -0.14, 95% CI -0.20; -0.08]) and greater decline in cognitive function (β -0.07, 95% CI -0.13; -0.01) from childhood to adulthood compared to those with lower suPAR levels. Finally, improvements in health habits between age 38 and 45 (smoking cessation or increased physical activity) were associated with less steep increases in suPAR levels over those years. Our findings provide initial support for the utility of suPAR in studying the role of chronic inflammation in accelerated aging and functional decline.

scholarly journals The Gut Microbiome and Metabolomics Profiles of Restricting and Binge-Purging Type Anorexia Nervosa

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 507
Author(s):  
Alessio Maria Monteleone ◽  
Jacopo Troisi ◽  
Gloria Serena ◽  
Alessio Fasano ◽  
Riccardo Dalle Grave ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Gut Microbiome ◽  
Small Sample Size ◽  
Secondary Analysis ◽  
Small Sample ◽  
Healthy Controls ◽  
Gut Dysbiosis ◽  
Patient Groups ◽  
Relative Abundances ◽  
Gut Microorganisms

Alterations in the gut microbiome and fecal metabolites have been detected in anorexia nervosa (AN), but differences in those profiles between restricting AN (ANR) and binge-purging AN (ANBP) type have not been explored. We made a secondary analysis of our previous data concerning microbiome and metabolomics profiles of 17 ANR women, six ANBP women and 20 healthy controls (HC). Twelve fecal metabolites differentiating ANR patients, ANBP patients and HC were identified. Both patient groups showed decreased intra-individual bacterial richness with respect to healthy controls (HC). Compared to ANR subjects, ANBP patients had a significant increase in relative abundances of Bifidobacterium, Bifidobacteriaceae, Bifidobacteriales, and Eubacteriacae and a significant decrease in relative abundances of Odoribacter, Haemophilus, Pasteurellaceae, and Pasteurellales. The heatmaps of the relationships of selected fecal metabolites with microbial families showed different structures among the three groups, with the heatmap of ANBP patients being drastically different from that of HC, while that of ANR patients resulted more similar to HC. These findings, although preliminary because of the relatively small sample size, confirm the occurrence of different gut dysbiosis in ANR and ANBP and demonstrate different connections between gut microorganisms and fecal metabolites in the two AN types.

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