scholarly journals Gut Microbiota Predicts Healthy Late-Life Aging in Male Mice

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3290
Author(s):  
Shanlin Ke ◽  
Sarah J. Mitchell ◽  
Michael R. MacArthur ◽  
Alice E. Kane ◽  
David A. Sinclair ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Aging Process ◽  
Healthy Aging ◽  
Frailty Index ◽  
Machine Learning Techniques ◽  
Age Related ◽  
Rate Of Increase ◽  
Reduced Rate ◽  
Compositional Patterns ◽  
Old Mice

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 significantly reduced rate of increase in the frailty index (FI), a well-established indicator of aging. We observed significant alterations in diversity, as well as 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.

scholarly journals Gut Microbiota predicts Healthy Late-life Aging in Male Mice

2021 ◽  
Author(s):  
Shanlin Ke ◽  
Sarah J. Mitchell ◽  
Michael R. MacArthur ◽  
Alice E Kane ◽  
David A. Sinclair ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Aging Process ◽  
Healthy Aging ◽  
Bacterial Load ◽  
Frailty Index ◽  
Machine Learning Techniques ◽  
Age Related ◽  
Learning Techniques ◽  
Compositional Patterns ◽  
Old Mice

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.

scholarly journals A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Lu Wu ◽  
Tiansheng Zeng ◽  
Angelo Zinellu ◽  
Salvatore Rubino ◽  
David J. Kelvin ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Healthy Aging ◽  
High Capacity ◽  
Functional Independence ◽  
Metagenomic Sequencing ◽  
Bifidobacterium Adolescentis ◽  
Content Type ◽  
Age Related ◽  
Genes Encoding ◽  
Functional Profiles

ABSTRACT Sardinia, Italy, has a high prevalence of residents who live more than 100 years. The reasons for longevity in this isolated region are currently unknown. Gut microbiota may hold a clue. To explore the role gut microbiota may play in healthy aging and longevity, we used metagenomic sequencing to determine the compositional and functional differences in gut microbiota associated with populations of different ages in Sardinia. Our data revealed that the gut microbiota of both young and elderly Sardinians shared similar taxonomic and functional profiles. A different pattern was found in centenarians. Within the centenarian group, the gut microbiota was correlated with the functional independence measurement of the host. Centenarians had a higher diversity of core microbiota species and microbial genes than those in the young and elderly. We found that the gut microbiota in Sardinian centenarians displayed a rearranged taxonomic pattern compared with those of the young and elderly, featured by depletion of Faecalibacterium prausnitzii and Eubacterium rectale and enriched for Methanobrevibacter smithii and Bifidobacterium adolescentis. Moreover, functional analysis revealed that the microbiota in centenarians had high capacity for central metabolism, especially glycolysis and fermentation to short-chain fatty acids (SCFAs), although the gut microbiota in centenarians was low in genes encoding enzymes involved in degradation of carbohydrates, including fibers and galactose. IMPORTANCE The gut microbiota has been proposed as a promising determinant for human health. Centenarians as a model for extreme aging may help us understand the correlation of gut microbiota with healthy aging and longevity. Here we confirmed that centenarians had microbiota elements usually associated with benefits to health. Our finding of a high capacity of glycolysis and related SCFA production represented a healthy microbiome and environment that is regarded as beneficial for host gut epithelium. The low abundance of genes encoding components of pathways involved in carbohydrate degradation was also found in the gut microbiota of Sardinian centenarians and is often associated with poor gut health. Overall, our study here represents an expansion of previous research investigating the age-related changes in gut microbiota. Furthermore, our study provides a new prospective for potential targets for gut microbiota intervention directed at limiting gut inflammation and pathology and enhancing a healthy gut barrier.

scholarly journals The Roles of the Gut Microbiota and Chronic Low-Grade Inflammation in Older Adults With Frailty

2021 ◽  
Vol 11 ◽  
Author(s):  
YuShuang Xu ◽  
XiangJie Liu ◽  
XiaoXia Liu ◽  
Di Chen ◽  
MengMeng Wang ◽  
...  
Keyword(s):  
Older Adults ◽  
Gut Microbiota ◽  
Chronic Inflammation ◽  
Healthy Aging ◽  
Low Grade ◽  
Age Related ◽  
Composition Structure ◽  
Low Grade Inflammation

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty.

scholarly journals AGE-RELATED ELEVATED CD4+ T HELPER 17 CELL RESPONSE PROMOTES PROSTATE CANCER CELL GROWTH, MIGRATION, AND INVASION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S879-S879
Author(s):  
Qiuyang Zhang ◽  
Sen Liu ◽  
Bing Zhang ◽  
Elizabeth Norton ◽  
S Michal Jazwinski ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
T Cells ◽  
Th17 Cell ◽  
Aging Process ◽  
Conditioned Media ◽  
Migration And Invasion ◽  
T Helper ◽  
T Helper 17 ◽  
Age Related ◽  
Old Mice

Abstract Age is the most important risk factor for prostate cancer (PCa). But, how age contributes to PCa remains unknown. Interleukin-17 (IL-17) -producing CD4+ T helper 17 (Th17) cells play a critical role in inflammatory diseases. It is often elevated in aging humans and mice, however, whether aging affects Th17 cell function and subsequent PCa risk increase is unclear. In this study, we investigated the role of CD4+ T cells in PCa cell growth during the aging process. Splenic T cells were isolated and purified into CD4+CD25- T cells from young and old mice, then cultured in the presence of plate-bound anti-CD3/anti-CD28. Four days later, the cells were re-stimulated with PMA and ionomycin in the presence of brefeldin A for 4 hours and then were collected and used for flow cytometry and/or qPCR. The supernatant (conditioned media) from young and old cultures was collected and used in subsequent experiments. Flow and qPCR results showed that 17-producing T cells and associated cytokines were significantly increased in old mice compared to young mice. When PCa cell lines (LNCaP, DU-145, and PC3) were treated by the conditioned media for 48 and 72 hours. The cell proliferation, migration, and invasion, as well as the activation of NF-B signaling in PCa cells, were significantly increased after exposure to the conditioned media from aged mice, compared to that from young mice. These results indicated that age-related CD4+ Th17 cell responses are elevated in mice in the aging process and play an important role in PCa growth.

Individual DNA Methylation Profile is Correlated with Age and can be Targeted to Modulate Healthy Aging and Longevity

2019 ◽  
Vol 25 (39) ◽  
pp. 4139-4149 ◽  
Author(s):  
Francesco Guarasci ◽  
Patrizia D'Aquila ◽  
Alberto Montesanto ◽  
Andrea Corsonello ◽  
Dina Bellizzi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mitochondrial Dna ◽  
Aging Process ◽  
Healthy Aging ◽  
Nuclear Dna ◽  
Epigenetic Modification ◽  
Biological Aging ◽  
Biomarkers Of Aging ◽  
Age Related

: Patterns of DNA methylation, the best characterized epigenetic modification, are modulated by aging. In humans, different studies at both site-specific and genome-wide levels have reported that modifications of DNA methylation are associated with the chronological aging process but also with the quality of aging (or biological aging), providing new perspectives for establishing powerful biomarkers of aging. : In this article, the role of DNA methylation in aging and longevity has been reviewed by analysing literature data about DNA methylation variations occurring during the lifetime in response to environmental factors and genetic background, and their association with the aging process and, in particular, with the quality of aging. Special attention has been devoted to the relationship between nuclear DNA methylation patterns, mitochondrial DNA epigenetic modifications, and longevity. Mitochondrial DNA has recently been reported to modulate global DNA methylation levels of the nuclear genome during the lifetime, and, in spite of the previous belief, it has been found to be the target of methylation modifications. : Analysis of DNA methylation profiles across lifetime shows that a remodeling of the methylome occurs with age and/or with age-related decline. Thus, it can be an excellent biomarker of aging and of the individual decline and frailty status. The knowledge about the mechanisms underlying these modifications is crucial since it might allow the opportunity for targeted treatment to modulate the rate of aging and longevity.

scholarly journals Small extracellular vesicles from young mice prevent frailty and improve healthspan in old mice.

2021 ◽  
Author(s):  
Jorge Sanz-Ros ◽  
Cristina Mas-Bargues ◽  
Daniel Monleon ◽  
Mar Dromant ◽  
Aksinya Derevyanko ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Healthy Aging ◽  
Motor Coordination ◽  
Frailty Index ◽  
Functional Improvement ◽  
Index Analysis ◽  
Increased Risk ◽  
Adipose Mesenchymal Stem Cells ◽  
Old Mice ◽  
Insight Into

Aging is associated with an increased risk of frailty, disability, comorbidities, institutionalization, falls, fractures, hospitalization, and mortality. Searching for strategies to delay the degenerative changes associated with aging and frailty is interesting. We treated old animals intravenously with small extracellular vesicles (sEVs) derived from adipose mesenchymal stem cells (ADSCs) of young animals, and we found an improvement of several functional parameters usually altered with aging, such as motor coordination, grip strength, fatigue resistance, fur regeneration, and renal function. Frailty index analysis showed that 40% of old control mice were frail, whereas none of the old ADSCs-sEVs treated mice were. Molecular and structural benefits in muscle and kidney accompanied this functional improvement. ADSCs-sEVs induced pro-regenerative effects and a decrease in oxidative stress, inflammation, and senescence markers. The metabolome of treated mice changed to a youth-like pattern. Finally, we gained some insight into the miRNAs contained in sEVs that might be, at least in part, responsible for the effects observed. We propose that young sEVs treatment can be beneficial against frailty and therefore can promote healthy aging.

scholarly journals Drivers of Frailty from Adulthood into Old Age: Results from a 27-year Longitudinal Population-Based Study in Sweden

2019 ◽  
Author(s):  
Emma Raymond ◽  
Chandra A. Reynolds ◽  
Anna K. Dahl Aslan ◽  
Deborah Finkel ◽  
Malin Ericsson ◽  
...  
Keyword(s):  
Social Support ◽  
Strong Predictor ◽  
Frailty Index ◽  
Population Based ◽  
Overweight And Obesity ◽  
Rate Of Change ◽  
Growth Curve Analysis ◽  
Age Related ◽  
Rate Of Increase ◽  
Latent Growth Curve Analysis

AbstractBackgroundFrailty is a strong predictor of adverse aging outcomes. However, the longitudinal drivers of frailty are not well understood. This study aimed at investigating the longitudinal trajectories of a frailty index (FI) from adulthood to late life and identifying the predictors of the level and rate of change in FI.MethodsAn age-based latent growth curve analysis was performed in the Swedish Adoption/Twin Study of Aging (N=1,842; aged 29-102 years) using data from up to 15 measurement waves across 27 years. A 42-item FI was used to measure frailty at each wave.ResultsA bilinear, two-slope model with a turning point at age 65 best described the age-related change in FI, showing that the rate of increase in frailty was more than twice as fast after age 65. Underweight, obesity, female sex, overweight, being separated from one’s co-twin during childhood, smoking, poor social support and low physical activity were associated with a higher level of FI at age 65, with underweight having the largest effect size. When tested as time-varying predictors, underweight and higher social support were associated with a steeper increase in FI before age 65, whereas overweight and obesity were associated with less steep increase in FI after age 65.ConclusionsPredictors for the level and rate of change in frailty are largely actionable and could provide targets for intervention. Underweight increased the risk of higher FI trajectory until age 65, whereas being overweight or obese were associated with slower progression of frailty towards the oldest ages.

scholarly journals Physical performance is enhanced in old mice fed a short term diet medicated with rapamycin, acarbose, and phenylbutyrate

2021 ◽  
Vol 3 (1) ◽  
pp. 12-13
Author(s):  
Megan Ellis ◽  
◽  
Warren Ladiges ◽  
Zhou Jiang
Keyword(s):  
Grip Strength ◽  
Physical Performance ◽  
Healthy Aging ◽  
Term Treatment ◽  
Drug Cocktail ◽  
Short Term ◽  
Short Term Treatment ◽  
Full Dose ◽  
Age Related ◽  
Old Mice

Loss of physical performance, as seen in humans by decreased grip strength and overall physical fitness, is generally accepted to be a consequence of aging. Treatments to delay or reduce these changes or increase resilience to them are generally not available. In this preliminary study, 20-month-old male and female C57BL/6 mice were given either a standard mouse diet or a formulated mouse diet containing rapamycin (14 ppm), acarbose (1000 ppm), and phenylbutyrate (1000 ppm), or a diet containing one half dose of each drug, for 3 months. At the end of the study, performance on a rotarod and grip strength test was compared. In general, mice fed the full dose drug cocktail diet performed better on these assays, with significant improvements in rotarod performance in females fed the full dose cocktail and in grip strength in males fed the full dose cocktail, and females fed the low dose cocktail. These observations provide support for the concept that short term treatment with a cocktail of drugs that targets multiple aging pathways can increase resilience to aging, and suggests that this prototype cocktail could be part of a clinical therapeutic strategy for delaying age-related loss of physical performance in people. Keywords: Healthy aging, physical performance, aging processes, anti-aging drug cocktail, rapamycin, acarbose, phenylbutyrate, aging mice

scholarly journals AGE-RELATED CHANGES IN THE MUSCLE SECRETOME

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S101-S101
Author(s):  
Ning Zhang ◽  
Susan Weintraub ◽  
Nicolas Musi
Keyword(s):  
Mass Spectrometry ◽  
Aging Process ◽  
Young Group ◽  
The Body ◽  
Age Related ◽  
Secretion Profile ◽  
And Function ◽  
Old Mice ◽  
Body Support ◽  
Age Related Changes

Abstract Skeletal muscle is one of the most abundant tissues in the body. In addition to its key roles in body support, movement and metabolic homeostasis, muscle also functions as an endocrine/secretory organ producing and releasing proteins into the circulation that modulate distant tissues (i.e. myokines). Considering that muscle mass and function changes with advancing age, here we tested the hypothesis that aging alters the muscle secretome profile. After euthanasia, soleus muscles from sedentary young and old mice were dissected, and incubated in oxygenated KRB buffer for 2 h. The buffer was subjected to in-gel trypsin-digestion and peptides analyzed by mass spectrometry. The concentration of 36 proteins were significantly (P<0.05) elevated in the young vs. the old group. In contrast, only 7 proteins were significantly elevated in the old group. Some notable differences include those in HSPA1B and HSPA5 that were detected only in the young group. HSPA8 also was significantly elevated by 1.8-fold (P<0.05) in the young versus the old group. Another prominent difference between groups involved translationally controlled tumor protein (TCTP), a critical regulator of apoptosis/carcinogenesis, that was elevated by 7-fold in the young vs. the old group (P<0.05). These results indicate that aging alters the muscle secretion profile. Identified differences in the muscle secretome could reflect intrinsic changes in muscle cells with age. Because these myokines are released into the circulation, it is also possible that myokine secretion is a regulated cellular process by which muscle communicates and modulates the aging process in distant tissues.

scholarly journals Aging progression of human gut microbiota

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Congmin Xu ◽  
Huaiqiu Zhu ◽  
Peng Qiu
Keyword(s):  
Microbial Community ◽  
Gut Microbiota ◽  
Human Health ◽  
Aging Process ◽  
Positive Impact ◽  
Age Groups ◽  
Individual Species ◽  
Human Gut ◽  
Human Gut Microbiota ◽  
Age Related

Abstract Background Human gut microbiota are important for human health and have been regarded as a “forgotten organ”, whose variation is closely linked with various factors, such as host genetics, diet, pathological conditions and external environment. The diversity of human gut microbiota has been correlated with aging, which was characterized by different abundance of bacteria in various age groups. In the literature, most of the previous studies of age-related gut microbiota changes focused on individual species in the gut community with supervised methods. Here, we aimed to examine the underlying aging progression of the human gut microbial community from an unsupervised perspective. Results We obtained raw 16S rRNA sequencing data of subjects ranging from newborns to centenarians from a previous study, and summarized the data into a relative abundance matrix of genera in all the samples. Without using the age information of samples, we applied an unsupervised algorithm to recapitulate the underlying aging progression of microbial community from hosts in different age groups and identify genera associated to this progression. Literature review of these identified genera indicated that for individuals with advanced ages, some beneficial genera are lost while some genera related with inflammation and cancer increase. Conclusions The multivariate unsupervised analysis here revealed the existence of a continuous aging progression of human gut microbiota along with the host aging process. The identified genera associated to this aging process are meaningful for designing probiotics to maintain the gut microbiota to resemble a young age, which hopefully will lead to positive impact on human health, especially for individuals in advanced age groups.

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