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Exercise Training Reduces Inflammation of Adipose Tissue in the Elderly: Cross-Sectional and Randomized Interventional Trial.
Čížková, T, Štěpán, M, Daďová, K, Ondrůjová, B, Sontáková, L, Krauzová, E, Matouš, M, Koc, M, Gojda, J, Kračmerová, J, et al
The Journal of clinical endocrinology and metabolism. 2020;(12)
Abstract
CONTEXT Metabolic disturbances and a pro-inflammatory state associated with aging and obesity may be mitigated by physical activity or nutrition interventions. OBJECTIVE The aim of this study is to assess whether physical fitness/exercise training (ET) alleviates inflammation in adipose tissue (AT), particularly in combination with omega-3 supplementation, and whether changes in AT induced by ET can contribute to an improvement of insulin sensitivity and metabolic health in the elderly. DESIGN, PARTICIPANTS, MAIN OUTCOME MEASURES The effect of physical fitness was determined in cross-sectional comparison of physically active/physically fit (trained) and sedentary/less physically fit (untrained) older women (71 ± 4 years, n = 48); and in double-blind randomized intervention by 4 months of ET with or without omega-3 (Calanus oil) supplementation (n = 55). Physical fitness was evaluated by spiroergometry (maximum graded exercise test) and senior fitness tests. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Samples of subcutaneous AT were used to analyze mRNA gene expression, cytokine secretion, and immune cell populations. RESULTS Trained women had lower mRNA levels of inflammation and oxidative stress markers, lower relative content of CD36+ macrophages, and higher relative content of γδT-cells in AT when compared with untrained women. Similar effects were recapitulated in response to a 4-month ET intervention. Content of CD36+ cells, γδT-cells, and mRNA expression of several inflammatory and oxidative stress markers correlated to insulin sensitivity and cardiorespiratory fitness. CONCLUSIONS In older women, physical fitness is associated with less inflammation in AT. This may contribute to beneficial metabolic outcomes achieved by ET. When combined with ET, omega-3 supplementation had no additional beneficial effects on AT inflammatory characteristics.
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Monocyte and T Cell Immune Phenotypic Profiles Associated With Age Advancement Differ Between People With HIV, Lifestyle-Comparable Controls and Blood Donors.
De Francesco, D, Sabin, CA, Reiss, P, Kootstra, NA
Frontiers in immunology. 2020;:581616
Abstract
MOTIVATION People with HIV on successful antiretroviral therapy show signs of premature aging and are reported to have higher rates of age-associated comorbidities. HIV-associated immune dysfunction and inflammation have been suggested to contribute to this age advancement and increased risk of comorbidities. METHOD Partial least squares regression (PLSR) was used to explore associations between biological age advancement and immunological changes in the T cell and monocyte compartment in people with HIV (n=40), comparable HIV-negative individuals (n=40) participating in the Comorbidity in Relation to AIDS (COBRA) cohort, and blood donors (n=35). RESULTS We observed that age advancement in all three groups combined was associated with a monocyte immune phenotypic profile related to inflammation and a T cell immune phenotypic associated with immune senescence and chronic antigen exposure. Interestingly, a unique monocyte and T cell immune phenotypic profile predictive for age advancement was found within each group. An inflammatory monocyte immune phenotypic profile associated with age advancement in HIV-negative individuals, while the monocyte profile in blood donors and people with HIV was more reflective of loss of function. The T cell immune phenotypic profile in blood donors was related to loss of T cell function, whereas the same set of markers were related to chronic antigen stimulation and immune senescence in HIV-negative individuals. In people with HIV, age advancement was related to changes in the CD4+ T cell compartment and more reflective of immune recovery after cART treatment. IMPACT The identified monocyte and T cell immune phenotypic profiles that were associated with age advancement, were strongly related to inflammation, chronic antigen exposure and immune senescence. While the monocyte and T cell immune phenotypic profile within the HIV-negative individuals reflected those observed in the combined three groups, a distinct profile related to immune dysfunction, was observed within blood donors and people with HIV. These data suggest that varying exposures to lifestyle and infection-related factors may be associated with specific changes in the innate and adaptive immune system, that all contribute to age advancement.
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The Role of Prevention in Healthy Aging.
Sharda, N, Wong, S, White, H
Clinics in geriatric medicine. 2020;(4):697-711
Abstract
This article explores the role of prevention in healthy aging from the perspective of individualized prevention in the clinic and population-based prevention with system-level support. The traditional medical model has significant limitations to effectively target impactful outcomes related to geriatric syndromes that encompass debility, frequent hospitalizations, loss of independence, and disease progression. This article reviews aspects of the clinic visit and subsequent interventions, such as immunizations and screenings, that promote disease and disability prevention. Finally, we review the value of Population Health Management as a model of care for delivering population-based, system-level supported, patient-centered health care plans.
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The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence.
DeJong, EN, Surette, MG, Bowdish, DME
Cell host & microbe. 2020;(2):180-189
Abstract
The gut microbiota changes with age, but it is not clear to what degree these changes are due to physiologic changes, age-associated inflammation or immunosenescence, diet, medications, or chronic health conditions. Observational studies in humans find that there are profound differences between the microbiomes of long-lived and frail individuals, but the degree to which these differences promote or prevent late-life health is unclear. Studies in model organisms demonstrate that age-related microbial dysbiosis causes intestinal permeability, systemic inflammation, and premature mortality, but identifying causal relationships have been challenging. Herein, we review how physiological and immune changes contribute to microbial dysbiosis and the degree to which microbial dysbiosis contributes to late-life health conditions. We discuss the features of the aging microbiota that make it more amenable to diet and pre- and probiotic interventions. Health interventions that promote a diverse microbiome could influence the health of older adults.
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Does eNOS derived nitric oxide protect the young from severe COVID-19 complications?
Guan, SP, Seet, RCS, Kennedy, BK
Ageing research reviews. 2020;:101201
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Abstract
The COVID-19 pandemic poses an imminent threat to humanity, especially to the elderly. The molecular mechanisms underpinning the age-dependent disparity for disease progression is not clear. COVID-19 is both a respiratory and a vascular disease in severe patients. The damage endothelial system provides a good explanation for the various complications seen in COVID-19 patients. These observations lead us to suspect that endothelial cells are a barrier that must be breached before progression to severe disease. Endothelial intracellular defences are largely dependent of the activation of the interferon (IFN) system. Nevertheless, low type I and III IFNs are generally observed in COVID-19 patients suggesting that other intracellular viral defence systems are also activated to protect the young. Intriguingly, Nitric oxide (NO), which is the main intracellular antiviral defence, has been shown to inhibit a wide array of viruses, including SARS-CoV-1. Additionally, the increased risk of death with diseases that have underlying endothelial dysfunction suggest that endothelial NOS-derived nitric oxide could be the main defence mechanism. NO decreases dramatically in the elderly, the hyperglycaemic and the patients with low levels of vitamin D. However, eNOS derived NO occurs at low levels, unless it is during inflammation and co-stimulated by bradykinin. Regrettably, the bradykinin-induced vasodilation also progressively declines with age, thereby decreasing anti-viral NO production as well. Intriguingly, the inverse correlation between the percentage of WT eNOS haplotype and death per 100K population could potentially explain the disparity of COVID-19 mortality between Asian and non-Asian countries. These changes with age, low bradykinin and NO, may be the fundamental reasons that intracellular innate immunity declines with age leading to more severe COVID-19 complications.
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Glycation and Oxidative Stress Increase Autoantibodies in the Elderly.
Khan, MWA, Al Otaibi, A, Sherwani, S, Khan, WA, Alshammari, EM, Al-Zahrani, SA, Saleem, M, Khan, SN, Alouffi, S
Molecules (Basel, Switzerland). 2020;(16)
Abstract
Aging causes gradual changes in free radicals, antioxidants, and immune-imbalance in the elderly. This study aims to understand links among aging, gluco-oxidative stress, and autoantibodies in asymptomatic individuals. In vitro glycation of human serum albumin (Gly-HSA) induces appreciable biochemical changes. Significant inhibition of advanced glycation end products (AGEs) formation was achieved using garlic extract (53.75%) and epigallocatechin-3-gallate from green tea (72.5%). Increased amounts of serum carbonyl content (2.42 ± 0.5) and pentosidine (0.0321 ± 0.0029) were detected in IV-S (S represent smokers) vs. IV group individuals. Direct binding ELISA results exhibited significantly high autoantibodies against Gly-HSA in group IV-S (0.55 ± 0.054; p < 0.001) and III-S (0.40 ± 0.044; p < 0.01) individuals as compared to the age matched subjects who were non-smokers (group IV and III). Moreover, high average percent inhibition (51.3 ± 4.1%) was obtained against Gly-HSA in IV-S group individuals. Apparent association constant was found to be high for serum immunoglobulin-G (IgG) from group IV-S (1.18 × 10-6 M) vs. serum IgG from IV group (3.32 × 10-7 M). Aging induced gluco-oxidative stress and AGEs formation may generate neo-epitopes on blood-proteins, contributing to production of autoantibodies in the elderly, especially smokers. Use of anti-glycation natural products may reduce age-related pathophysiological changes.
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The Gut Microbiome, Aging, and Longevity: A Systematic Review.
Badal, VD, Vaccariello, ED, Murray, ER, Yu, KE, Knight, R, Jeste, DV, Nguyen, TT
Nutrients. 2020;(12)
Abstract
Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but Akkermansia was most consistently reported to be relatively more abundant with aging, whereas Faecalibacterium, Bacteroidaceae, and Lachnospiraceae were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes.
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Gut dysbiosis and age-related neurological diseases; an innovative approach for therapeutic interventions.
Holmes, A, Finger, C, Morales-Scheihing, D, Lee, J, McCullough, LD
Translational research : the journal of laboratory and clinical medicine. 2020;:39-56
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Abstract
The gut microbiota is a complex ecosystem of bacteria, fungi, and viruses that acts as a critical regulator in microbial, metabolic, and immune responses in the host organism. Imbalances in the gut microbiota, termed "dysbiosis," often induce aberrant immune responses, which in turn disrupt the local and systemic homeostasis of the host. Emerging evidence has highlighted the importance of gut microbiota in intestinal diseases, and more recently, in age-related central nervous systems diseases, for example, stroke and Alzheimer's disease. It is now generally recognized that gut microbiota significantly influences host behaviors and modulates the interaction between microbiota, gut, and brain, via the "microbiota-gut-brain axis." Several approaches have been utilized to reduce age-related dysbiosis in experimental models and in clinical studies. These include strategies to manipulate the microbiome via fecal microbiota transplantation, administration of prebiotics and probiotics, and dietary interventions. In this review, we explore both clinical and preclinical therapies for treating age-related dysbiosis.
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Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis.
Omran, HM, Almaliki, MS
Journal of infection and public health. 2020;(9):1196-1201
Abstract
The aging-associated decline of biological functions represents an important contributor to the increase in morbidity and mortality of human beings. Of these biological functions deterioration; there is a significant decline in the heart function, impairments in the lungs gas exchange, and impairments in the immune function. Many alterations in the body humeral and cellular immune response were observed with ageing process: The circulating pro-inflammatory cytokines are increased, the naive lymphocytes are decreased, the numbers of the antigen-presenting cells areelevated and the overall response is impaired. In addition, ageing is associated with a progressive restriction in the telomere length. Telomeres are located at chromosomes ends and play an essential role in preserving chromosome stability. Also, telomere length is very important to the immune system, because of the high sensitivity of the immune cells to the shortening of telomeres. Telomeres shortening adversely affect the immune cells' function and developments. These adverse changes increased the susceptibility for severe infection, risk of hospitalization, and even death. Elderly COVID-19 patients are at a real risk of complications due to impaired immune function, cytokine storm and defective respiratory function. Administration of anti-ageing immunomodulation factors like Nicotinamide Adenine Dinucleotide NAD+ can minimize these changes through its potent immunomodulation and longevity effects. NAD+ has a direct inhibitory effect on PARP-1 and can prevent pro-inflammatory cytokines over-activation. Increasing the NAD+ level will also result in stabilizing telomeres and this has a positive impact on immune cells function.
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Pressure Injury Prevention Considerations for Older Adults.
Cowan, L, Broderick, V, Alderden, JG
Critical care nursing clinics of North America. 2020;(4):601-609
Abstract
There are well-documented physiologic changes that occur in the human body during the aging process, such as decreased body fat, decreased muscle mass, cellular senescence, changes in skin pH, decreased metabolism, decreased immune function, vascular changes, altered tissue perfusion, nutritional status changes, and poor hydration. These changes affect skin integrity and wound healing, and raise the risk of pressure-related skin injury. This article discusses aging as a risk factor for pressure injury (PrI). Topics include evidence for advancing age as a significant PrI risk factor, identifying pathophysiologic changes/mechanisms of aging, and specific PrI preventive interventions to consider in older adults.