scholarly journals Aerobic exercise attenuates frailty in aging male and female C57Bl/6 mice and effects systemic cytokines differentially by sex

2021 ◽  
Author(s):  
Elise S Bisset ◽  
Stefan Heinze-Milne ◽  
Scott A Grandy ◽  
Susan E Howlett
Keyword(s):  
Life Expectancy ◽  
Aerobic Exercise ◽  
Systemic Inflammation ◽  
Frailty Index ◽  
Biological Age ◽  
Beneficial Effects ◽  
Serum Cytokines ◽  
Cytokine Levels ◽  
The Impact ◽  
Pro Inflammatory Cytokines

Abstract Aerobic exercise is a promising intervention to attenuate frailty, but preclinical studies have used only male animals. We investigated the impact of voluntary aerobic exercise on frailty, biological age (FRIGHT clock), predicted life expectancy (AFRAID clock) and mortality in both sexes and determined whether exercise was associated with changes in inflammation. Older (21-23 months) male (n=12) and female (n=22) C57Bl/6 mice matched for baseline frailty scores were randomized into exercise (running wheel) and sedentary (no wheel) groups. Frailty index scores were measured biweekly (13 weeks), and 23 serum cytokines were measured at midpoint and endpoint. Exercise levels varied between mice but not between the sexes. Exercise had no effect on mortality, but it attenuated the development of frailty in both sexes (female=0.32±0.04 vs 0.21±0.01; p=0.005; male=0.30±0.02 vs. 0.22±0.02; p=0.042) and reduced frailty in older females after 10 weeks. FRIGHT scores were unaffected by exercise but increased with time in sedentary males indicating increased biological age. Exercise prevented the age-associated decline in AFRAID scores in older females such that exercised females had a longer life expectancy. We investigated whether aerobic exercise was associated with changes in systemic inflammation. Cytokine levels were not affected by exercise in males, but levels of pro-inflammatory cytokines were positively correlated with the frequency of exercise in females. Despite increases in systemic inflammation, exercise reduced frailty and increased lifespan in older females. Thus, voluntary aerobic exercise, even late in life, has beneficial effects on health in both sexes but may be especially helpful in older females.

scholarly journals Aerobic Exercise Induces Alternative Splicing of Neurexins in Frontal Cortex

2021 ◽  
Vol 6 (2) ◽  
pp. 48
Author(s):  
Elisa Innocenzi ◽  
Ida Cariati ◽  
Emanuela De Domenico ◽  
Erika Tiberi ◽  
Giovanna D’Arcangelo ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Aerobic Exercise ◽  
Frontal Cortex ◽  
Molecular Mechanisms ◽  
Splice Variants ◽  
Brain Regions ◽  
Synaptic Function ◽  
Molecular Changes ◽  
Beneficial Effects ◽  
The Impact

Aerobic exercise (AE) is known to produce beneficial effects on brain health by improving plasticity, connectivity, and cognitive functions, but the underlying molecular mechanisms are still limited. Neurexins (Nrxns) are a family of presynaptic cell adhesion molecules that are important in synapsis formation and maturation. In vertebrates, three-neurexin genes (NRXN1, NRXN2, and NRXN3) have been identified, each encoding for α and β neurexins, from two independent promoters. Moreover, each Nrxns gene (1–3) has several alternative exons and produces many splice variants that bind to a large variety of postsynaptic ligands, playing a role in trans-synaptic specification, strength, and plasticity. In this study, we investigated the impact of a continuous progressive (CP) AE program on alternative splicing (AS) of Nrxns on two brain regions: frontal cortex (FC) and hippocampus. We showed that exercise promoted Nrxns1–3 AS at splice site 4 (SS4) both in α and β isoforms, inducing a switch from exon-excluded isoforms (SS4−) to exon-included isoforms (SS4+) in FC but not in hippocampus. Additionally, we showed that the same AE program enhanced the expression level of other genes correlated with synaptic function and plasticity only in FC. Altogether, our findings demonstrated the positive effect of CP AE on FC in inducing molecular changes underlying synaptic plasticity and suggested that FC is possibly a more sensitive structure than hippocampus to show molecular changes.

scholarly journals MACHINE LEARNING ANALYSIS OF MOUSE FRAILTY FOR PREDICTION OF BIOLOGICAL AGE AND LIFE EXPECTANCY

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S903-S903 ◽  
Author(s):  
Alice Kane ◽  
Michael B Schultz ◽  
Sarah Mitchell ◽  
Michael MacArthur ◽  
James Mitchell ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Dietary Intervention ◽  
Enzyme Inhibitor ◽  
Strong Predictor ◽  
Frailty Index ◽  
Biological Age ◽  
Chronological Age ◽  
Aging Research ◽  
Non Invasive ◽  
Median Error

Abstract In mammals, the lack of accurate biomarkers for biological age is a current limitation to identifying novel aging interventions. Molecular biomarkers including DNA methylation hold promise but are invasive and currently expensive. The Frailty Index (FI) quantifies the accumulation of health-related deficits and is fast, cheap, and non-invasive. Studies have demonstrated that FI correlates with age and mortality risk in mice and humans. However, the FI has not been modelled to directly predict biological age or life expectancy. We tracked aging male C57BL/6 mice until their natural deaths, scoring them longitudinally with the FI. We find that FI score correlates with and is predictive of age and that some but not all parameters of the FI are individually well-correlated with age. To better predict chronological age, we performed an elastic net regression on the FI termed FRIGHT (Frailty Inferred Geriatric Health Timeline) Age. FRIGHT Age is a strong predictor of age (r2=0.73, median error=47.5 days), but is not superior to chronological age at predicting life expectancy. To better predict mortality, we built a random forest model termed the AFRAID (Analysis of Frailty and Death) score, which predicted survival at multiple ages (r2=0.375, median error = 46.4 days). The FRIGHT and AFRAID models were responsive to chronic treatment with enalapril (30mg/kg/day), an angiotensin converting enzyme inhibitor that extends healthspan, and methionine restriction, a dietary intervention that extends healthspan and lifespan. Our findings underscore the value of assessing non-invasive biomarkers for aging research and may help speed the identification of aging interventions.

scholarly journals Relationship of Risk Factors for Metabolic-Associated Diseases with Biological Age

2021 ◽  
Vol 6 (5) ◽  
pp. 184-192
Author(s):  
O. V. Kolesnikova ◽  
◽  
O. E. Zaprovalna ◽  
A. V. Potapenko
Keyword(s):  
Risk Factors ◽  
Insulin Resistance ◽  
Life Expectancy ◽  
Premature Aging ◽  
Biological Age ◽  
World Health ◽  
Aged Patients ◽  
Associated Diseases ◽  
Pathological Conditions ◽  
The Impact

Assessment of the rate of aging is of great importance in modern medicine, since people of middle age may have a discrepancy between the calendar and biological age. Biological age is a measure of biological capabilities, which determines not only the past, but also the measures of the forthcoming life expectancy, as well as the risk of certain age-dependent diseases. Metabolic disorders, including hyperglycemia, dyslipidemia, insulin resistance and hyperinsulinemia induce interrelated processes in the vascular wall as well as increase oxidative stress, apoptosis, and vascular permeability therefore contributing to the development of premature aging. The purpose of the study was to establish the relationship between risk factors for metabolic-associated diseases and biological age. Materials and methods. The study involved 119 patients who were divided into 2 groups: 1 group (n = 67) – patients with moderate risk of cardiovascular disease in combination with metabolic-associated diseases (insulin resistance, obesity, hyperuricemia), group 2 (n = 52) – comparison group. Each group was divided into subgroups, depending on age categories: up to 45 years, from 45 years to 60 years (middle-aged patients according to the World Health Organization recommendations), from 60 to 75 years, over 75 years. Results and discussion. Premature aging is diagnosed on the basis of determining the biological age as an indicator of conformity (inconsistency) of the morphofunctional status of the individual to some statistical average development value of this age and sex group. Determination of risk factors for metabolic-associated diseases will effectively counteract the occurrence of pathological conditions and increase life expectancy in these patients. The article presents its own data on the association of risk factors for metabolic-associated diseases, such as smoking, excessive alcohol consumption, body mass index, elevated insulin levels and high levels of proatherogenic lipids, stress level with increasing biological age, both in the study and in the control groups, thus accelerating the rate of aging. Conclusion. Preventive strategies aimed at preventing the impact of risk factors for metabolic-associated diseases will effectively counteract the occurrence of pathological conditions, prevent cardiovascular events (myocardial infarction and cerebrovascular accident), thereby increasing life expectancy in these patients

scholarly journals Serum cytokine profiles in healthy nonhuman primates are blunted by sedation and demonstrate sexual dimorphism as detected by a validated multiplex immunoassay

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Laura Hocum Stone ◽  
Scott Hunter Oppler ◽  
Julia L. Nugent ◽  
Sarah Gresch ◽  
Bernhard J. Hering ◽  
...  
Keyword(s):  
Immune Responses ◽  
Nonhuman Primates ◽  
Rhesus Macaques ◽  
Clinical Settings ◽  
Model Design ◽  
Serum Cytokine ◽  
Serum Cytokines ◽  
Cytokine Levels ◽  
The Impact ◽  
Cytokine Profiling

AbstractCytokine profiling is a valuable tool for monitoring immune responses associated with disease and treatment. This study assessed the impact of sex and sedation on serum cytokines in healthy nonhuman primates (NHPs). Twenty-three cytokines were measured from serum using a bead-based multiplex assay. Assay validation for precision, sensitivity, recovery, linearity, and stability was performed. Samples from male and female cynomolgus and rhesus macaques either cooperating or sedated were compared. All cytokines except TNFα demonstrated acceptable sensitivity and precision, with variable recovery and linearity. IFNγ, IL-2, IL-5, IL-6, IL-8, IL-12/23 (p40), IL-13, IL-15, MCP-1, TGFα, VEGF met acceptance criteria; G-CSF, IL-4, IL-10, MIP1α, sCD40L were marginal. Higher cytokine levels were observed in females and cytokine levels were blunted in sedated NHPs when compared to awake cooperating NHPs. Significant differences observed in cytokines related to sex, species, or imposed by handling highlight the importance of model design on translational relevance for clinical settings.

HBOT Application at Cases of Gingival Inflammation

2019 ◽  
Author(s):  
Ilma Robo
Keyword(s):  
Root Resorption ◽  
Periodontal Diseases ◽  
Therapeutic Effects ◽  
Clinical Effects ◽  
Gingival Inflammation ◽  
Beneficial Effects ◽  
New Therapeutic Approaches ◽  
Short Period ◽  
Mechanical Therapy ◽  
The Impact

The treatment of periodontal diseases, mainly of their origin, with the most common clinical manifestation in form of gingival inflammation, is manifold and powerful, including: mechanical therapy, antibiotic, antiseptic and various approaches to treatment, which are recommended to be used within a short period of time. New therapeutic approaches have been proven as alternative treatment to conventional therapy, or in combination with conventional therapies, to reduce the number of periodontopathic pathogens in gingival sulcus. HBOT has a detrimental effect on periodontal microorganisms, as well as beneficial effects on the healing of periodontal tissue, increasing oxygen pressure in gingival pockets. Our study is aimed at reviewing the current published literature on hyperbaric oxygen therapy and focuses on role of HBOT as a therapeutic measure for the individual with periodontal disease in general and for the impact on the recovery of gingival inflammation. HBOT and periodontal treatment together, reduce up to 99% of the gram-negative anaerobic load of subgingival flora. HBOT, significantly reduces subgingival anaerobic flora. Clinical effects in 2-year follow-up of treated patients are sensitive. Reduction of gingival hemorrhage indexes, depth of peritoneum, plaque index, occurs in cases of combination of HBOT and detraction. Reduced load persists up to 2 months after therapy. The significant increase in connective tissue removal starts at the end of 2nd week, to achieve the maximum in week 3-6 of application. HBOT used for re-implantation, stimulates the healing of periodontal membrane, pulp, prevents root resorption, healing of periodontal lining tissues. HBOT, significantly reduces the hemorrhage index with 1.2 value difference, 0.7mm probe depth, reduces gingival fluid by 2. HGH exposure is increased by gingival blood flow, with a difference of 2 in measured value. The therapeutic effects of HBOT in the value of the evaluation index can be saved up to 1-year post treatment.

Relation between cognitive disorders and type of physical activity: Results of the FréLE cohort

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
C Dupré ◽  
N Barth ◽  
A El Moutawakkil ◽  
F Béland ◽  
F Roche ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Decline ◽  
Proportional Hazards ◽  
Cognitive Disorders ◽  
The Elderly ◽  
Cognitive Status ◽  
Global Test ◽  
Professional Activities ◽  
Beneficial Effects ◽  
The Impact

Abstract Background Few previous cohorts have studied the different type of physical activities and the degree of cognitive decline. The objective of this work was to analyze the leisure, domestic and professional activities with mild and moderate cognitive disorders in older people living in community. Methods The study used data from the longitudinal and observational study, FrèLE (FRagility: Longitudinal Study of Expressions). The collected data included: socio-demographic variables, lifestyle, and health status (frailty, comorbidities, cognitive status, depression). Cognitive decline was assessed by using: MMSE (Mini-Mental State Examination) and MoCA (Montreal Cognitive Assessment). MoCA was used with two cut-offs (26 and 17) so as to define mild and moderate cognitive disorders Physical activity was assessed by the PASE (Physical Activity Scale for the Elderly), structured in three sections: leisure, domestic and professional activities. Spline and proportional hazards regression models (Cox) were used to estimate the risk of cognitive disorders. Results At baseline, 1623 participants were included and the prevalence of cognitive disorders was 6.9% (MMSE) and 7.2% (MoCA), mild cognitive disorders was 71.3%. The mean age was 77 years, and 52% of the participants were women. After a 2 years long follow-up, we found 6.9% (MMSE) and 6% (MoCA) cognitive disorders on participants. Analyses showed that domestic activities were associated to cognitive decline (HR = 0.52 [0.28-0.94] for MMSE and HR = 0.48 [0.28-0.80] for MoCA). No association were found with leisure and professional activities, and no spline were significant with mild cognitive disorders. Conclusions Analysis showed a relationship between cognitive disorders and type of physical activity, thanks to the use of specific questionnaire of elderly and two global test of cognition. These findings will contribute to the debate on the beneficial effects of physical activity on cognition. Key messages This work allowed to compare two test of cognition and their link with physical activity. It contributes to the debate on the beneficial effects of physical activity on cognition. The work allowed us to see the effect of the different types of physical activity and the impact of the statistical method on the results.

scholarly journals Microstructure and Durability Performance of Mortars with Volcanic Powder from Calbuco Volcano (Chile) after 4 Hardening Years

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1751
Author(s):  
Rosa María Tremiño ◽  
Teresa Real-Herraiz ◽  
Viviana Letelier ◽  
José Marcos Ortega
Keyword(s):  
Water Absorption ◽  
Thermal Analyses ◽  
Length Change ◽  
Cement Industry ◽  
Chloride Diffusion ◽  
Beneficial Effects ◽  
State Diffusion ◽  
Calbuco Volcano ◽  
Reference Specimens ◽  
The Impact

One of the most popular ways to lessen the impact of the cement industry on the environment consists of substituting clinker by additions. The service life required for real construction elements is generally long, so it would be interesting to obtain information about the effects of new additions after a hardening period of several years. Analyzed here are the effects of the incorporation of volcanic ashes, coming from Calbuco volcano’s last eruption (Chile), as clinker replacement, in the durability and pore structure of mortars, after approximately 4 hardening years (1500 days), in comparison with reference specimens without additions. The substitution percentages of clinker by volcanic powder studied were 10% and 20%. The microstructure was characterized with mercury intrusion porosimetry and impedance spectroscopy. In order to evaluate the pozzolanic activity of the volcanic powder after 1500 days, differential thermal analyses were performed. Water absorption after immersion, steady-state diffusion coefficient and length change were also studied. In accordance with the results obtained, the 10% and 20% substitution of clinker by volcanic powder from the Calbuco volcano showed beneficial effects in the mortars after 4 years, especially regarding the microstructure and chloride diffusion, without noticeable influence in their water absorption.

scholarly journals Reproduction and biomarker responses of Eisenia fetida after exposure to imidacloprid in biochar-amended soil

Biochar ◽  
2021 ◽  
Author(s):  
Ngitheni Winnie-Kate Nyoka ◽  
Ozekeke Ogbeide ◽  
Patricks Voua Otomo
Keyword(s):  
Eisenia Fetida ◽  
Field Studies ◽  
Application Rate ◽  
Land Application ◽  
Acetylcholinesterase Inhibition ◽  
Beneficial Effects ◽  
Pesticide Pollution ◽  
The One ◽  
The Impact ◽  
Amended Soil

AbstractTerrestrial and aquatic ecosystems are increasingly threatened by pesticide pollution resulting from extensive use of pesticides, and due to the lack of regulatory measures in the developing world, there is a need for affordable means to lessen environmental effects. This study aimed to investigate the impact of biochar amendment on the toxicity of imidacloprid to life-cycle parameters and biomarker responses of the earthworm Eisenia fetida. E. fetida was exposed to 10% biochar-amended and non-amended OECD artificial soils spiked with 0, 0.75, 1.5, 2.25 and 3 mg imidacloprid/kg for 28 days. An LC50 of 2.7 mg/kg was only computed in the non-amended soil but not in the biochar-amended soil due to insignificant mortality. The EC50 calculated in the non-amended soil (0.92 mg/kg) for reproduction (fertility) was lower than the one computed in the biochar amended (0.98 mg/kg), indicating a decrease in toxicity in the biochar-amended substrate. Significant weight loss was observed at the two highest imidacloprid treatments in the non-amended soil and only at the highest treatment in the biochar-amended substrate, further highlighting the beneficial effects of biochar. Catalase activity decreased significantly at the two highest concentrations of non-amended soil. Yet, in the amended soil, the activity remained high, especially in the highest concentration, where it was significantly higher than the controls. This indicated more severe oxidative stress in the absence of biochar. In all non-amended treatments, there was a significant acetylcholinesterase inhibition, while lower inhibition percentages were observed in the biochar-amended soil. In most endpoints, the addition of biochar alleviated the toxic effects of imidacloprid, which shows that biochar has the potential to be useful in soil remediation. However, there is still a need for field studies to identify the most effective application rate of biochar for land application.

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