Age-Associated Glia Remodeling and Mitochondrial Dysfunction in Neurodegeneration: Antioxidant Supplementation as a Possible Intervention.

Aging induces substantial remodeling of glia, including density, morphology, cytokine expression, and phagocytic capacity. Alterations of glial cells, such as hypertrophy of lysosomes, endosomes and peroxisomes, and the progressive accumulation of lipofuscin, lipid droplets, and other debris have also been reported. These abnormalities have been associated with significant declines of microglial processes and reduced ability to survey the surrounding tissue, maintain synapses, and recover from injury. Similarly, aged astrocytes show reduced capacity to support metabolite transportation to neurons. In the setting of reduced glial activity, stressors and/or injury signals can trigger a coordinated action of microglia and astrocytes that may amplify neuroinflammation and contribute to the release of neurotoxic factors. Oxidative stress and proteotoxic aggregates may burst astrocyte-mediated secretion of pro-inflammatory cytokines, thus activating microglia, favoring microgliosis, and ultimately making the brain more susceptible to injury and/or neurodegeneration. Here, we discuss the contribution of microglia and astrocyte oxidative stress to neuroinflammation and neurodegeneration, highlight the pathways that may help gain insights into their molecular mechanisms, and describe the benefits of antioxidant supplementation-based strategies.

Acute and chronic effects of traditional and high-speed resistance training on blood pressure in older adults: A crossover study and systematic review and meta-analysis.

PURPOSE: The present study included two related investigations that explored the acute and chronic effects of high-speed resistance training (HSRT) on blood pressure (BP) in older adults. METHODS: The first study involved a randomized crossover study that compared the acute effects of traditional resistance exercise (TRT) and high-speed resistance training (HSRT) on hemodynamic parameters in frail older adults. Sixteen institutionalized frail older adults were recruited. BP was recorded before, over 1 h, and 24 h after the end of the experimental session. Participants performed 4 resistance exercises involving 4-8 sets with 4-10 repetitions at moderate intensity. The second study was a systematic review and meta-analysis of experimental studies that investigated the acute and chronic effects of HSRT on BP in older adults. Crossover, quasi-experimental, and randomized controlled trials that examined the effects of HSRT on BP in people aged 60+ years as a primary or secondary outcome were included. Studies were retrieved from MEDLINE, SPORTDiscuss, CINAHL, SCOPUS and AgeLine databases from inception through December 31, 2021. The risk of bias was evaluated using the Newcastle - Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on standard mean differences (SMD). RESULTS: In study 1, we observed that both TRT and HSRT caused post-exercise hypotension (PEH). However, systolic BP (SBP) was significantly lowered for up to 60 min after TRT, while it was only reduced 30 and 50 min after HSRT. There was no difference in SBP between resistance exercise protocols. A reduction in mean arterial pressure was only observed after TRT. In study 2, 1114 articles were identified, and 8 were included in the meta-analysis. Pooled analyses indicated that HSRT did not cause significant PEH. However, a significant reduction in SBP was observed after HSRT programs in comparison to controls (SMD = 0.61, P = 0.009) and baseline values (SMD = 2.03, P = 0.04). CONCLUSION: In study one, we observed that both TRT and HSRT caused systolic PEH in comparison to baseline in frail older adults. However, specific patterns were observed according to each type of RT. Indeed, a longer PEH in comparison to baseline was observed after TRT, whereas HSRT had greater reductions in comparison to CS. In addition, TRT had exclusive reductions in MAP. These results were not supported by our meta-analysis, given that no significant effects of an acute session of HSRT on office and ambulatorial BP were observed. On the other hand, our findings suggest that HSRT might significantly reduce SBP in older adults.

Acute Effects of Low- and High-Speed Resistance Exercise on Cognitive Function in Frail Older Nursing-Home Residents: A Randomized Crossover Study.

AIM: The present study investigated the acute effects of low- and high-speed resistance exercise on the cognitive function of frail older women living in nursing home. MATERIALS AND METHODS: Ten institutionalized frail older women were recruited. Rey Auditory Verbal Learning Test and Stroop test were performed before, immediately after, 1 h after, and 24 h after the end of the experimental session. Participants randomly performed low- and high-speed resistance exercise and a control session. Exercise sessions were composed of 4 resistance exercises with 4-8 sets of 4-10 repetitions at moderate intensity. RESULTS: Results indicated that the performance of Rey Auditory Verbal Learning Test was similarly increased immediately after both low- and high-speed resistance exercises. However, only improvements elicited by low-speed resistance exercise remained significant 1 h after the end of the exercise session. No acute effects of resistance exercise were observed on Stroop performance. CONCLUSION: Our findings indicated that both low- and high-speed resistance exercises acutely increased episodic memory in frail older women, whereas no changes on Stroop were observed.

Master athletes have longer telomeres than age-matched non-athletes. A systematic review, meta-analysis and discussion of possible mechanisms.

The aim of this systematic review and meta-analysis was 1) to assess whether master athletes have longer telomeres than age-matched non-athletes and 2) discuss possible underlying mechanisms underlying telomere length preservation in master athletes. A literature search was performed in PubMed, Web of Science, Scopus and SPORTDiscus up to August 2020. Only original articles published in peer-reviewed journals that compared telomere length between master athletes and aged-matched non-athletes were included. Eleven studies fulfilled eligibility criteria and were included in the final analysis. Overall, 240 master athletes (51.9±7.5 years) and 209 age-matched non-athletes (50.1±9.1 years) were analyzed. Master athletes had been participating in high-level competitions for approximately 16.6 years. Pooled analyses revealed that master athletes had longer telomeres than aged-matched non-athletes (SMD=0.89; 95% CI=0.45 to 1.33; p<0.001). Master athletes showed lower pro-oxidant damage (SMD=0.59; 95% CI=0.26 to 0.91; p<0.001) and higher antioxidant capacity (SMD=-0.46; 95% CI=-0.89 to -0.03; p=0.04) than age-matched non-athletes. Further, greater telomere length in master athletes is associated with lower oxidative stress and chronic inflammation, and enhanced shelterin protein expression and telomerase activity. In conclusion, 1) master athletes have longer telomeres than age-matched non-athletes, which may be the result of 2) lower levels of oxidative stress and chronic inflammation, and elevated shelterin expression and telomerase activity.

Identification of biomarkers for physical frailty and sarcopenia through a new multi-marker approach: results from the BIOSPHERE study.

Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a "core" biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1ß, with peculiar signatures in men and women.SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.

Age- and Gender-Related Changes in Physical Function in Community-Dwelling Brazilian Adults Aged 50 to 102 Years.

BACKGROUND AND PURPOSE: Cutoff points for physical function tests are commonly used in clinical practice for the evaluation, monitoring, and treatment of older adults. Previous studies have shown that, while age-related patterns of muscle strength change are similar between ethnic groups, strength values differ significantly independent of age. Whether the same applies to other physical function tests is presently unclear. This study investigated age- and gender-related changes of performance on a battery of physical function tests in Brazilian community dwellers. METHODS: The study followed a cross-sectional design. Participants were community-dwelling adults. Candidates were considered eligible if they were 18 years or older, lived independently, and possessed sufficient physical and cognitive abilities to perform all of the measurements required by the protocol. Physical function tests included isometric handgrip (IHG), 5 times sit-to-stand (5×STS) test, Timed Up and Go, 1-leg stance, and walking speed (WS) at usual and fast pace. RESULTS: Two-thousand eight-hundred and four people were enrolled. Mean age was 68.0 (7.0) years (range 50-102 years), and 2262 (80.7%) were women. Men displayed better IHG and balance, while women showed higher performance on the 5×STS and WS tests. A gender-specific pattern of decline in physical performance was observed. Specifically, women showed a linear age-dependent decline in all tests. In men, only in the IHG, 1-leg stance, and WS test at a fast pace was there a linear decline with age. In both genders, the lowest mean values of physical function tests were higher than the proposed cutoffs for sarcopenia. DISCUSSION AND CONCLUSIONS: Our findings indicate that the performance on different physical function tests decreases with advancing age in Brazilian adults, following a gender-specific pattern. In none of the tests did the lowest mean values reach the cutoffs for sarcopenia. This suggests that region-specific cutoffs might be necessary to identify older people at risk of adverse events.

Protein Intake and Frailty: A Matter of Quantity, Quality, and Timing.

Frailty is a geriatric syndrome that refers to a state of reduced resiliency to stressful events that occurs in response to physiological and/or psychosocial detriments. Frailty is a predictor of poor prognosis, given that frail older adults are at higher risk of many adverse health-related events. Hence, the identification of potential strategies to prevent the development and progression of frailty is of extreme importance for avoiding its negative outcomes. An adequate protein consumption is advocated as a possible intervention for the management of frailty in older adults due to its effects on muscle mass and physical function. However, empirical evidence is still needed to support this proposition. On the other hand, substantial evidence from observational studies has provided important information on the association between frailty and dietary protein-related parameters. Here, we provide a narrative review of the current literature regarding the association between protein intake (amount (how much?), quality (what type?), and distribution across meals (when?)) and frailty-related parameters. The ultimate aim of this work is to offer practical, evidence-based indications to healthcare professionals responsible for the care of frail older adults.

Association between Dietary Habits and Physical Function in Brazilian and Italian Older Women.

The present study investigated and compared the patterns of dietary protein intake and physical function in Brazilian and Italian older women. Seventy-five Brazilian older women were recruited in a community senior center. Fifty-three age-matched Italian older women were selected from participants of the Longevity check-up (Lookup) 7+ study. In both samples, physical performance was evaluated by isometric handgrip strength (IHG) and five-time sit-to-stand (5 × STS) tests, while diet was assessed through 24-h recall. Results indicated that Brazilian women had a higher intake of plant-based protein (52.7% vs. 30.5% kcal), while Italian women consumed greater amounts of animal-derived protein (29.7% vs. 41.5% kcal). In Brazilian women, the binary logistic regression analysis indicated that body weight-adjusted protein consumption was associated with IHG adjusted by body mass index and with 5 × STS performance. In the Italian sample, the intake of isoleucine, leucine, and valine was significantly associated with 5 × STS performance. Our findings indicate that Brazilian and Italian community-dwelling older women show different patterns of protein intake, with higher consumption of plant-based protein in the Brazilian sample and higher ingestion of animal-derived protein in the Italian subgroup. These dietary patterns may differentially impact the relationship between physical function and protein intake observed in Brazilian and Italian older women.

The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) Study: Rationale, Design and Methods.

Mild cognitive impairment (MCI), also termed mild neurocognitive disorder, includes a heterogeneous group of conditions characterized by declines in one or more cognitive domains greater than that expected during "normal" aging but not severe enough to impair functional abilities. MCI has been associated with an increased risk of developing dementia and even considered an early stage of it. Therefore, noninvasively accessible biomarkers of MCI are highly sought after for early identification of the condition. Systemic inflammation, metabolic perturbations, and declining physical performance have been described in people with MCI. However, whether biological and functional parameters differ across MCI neuropsychological subtypes is presently debated. Likewise, the predictive value of existing biomarkers toward MCI conversion into dementia is unclear. The "develOpment of metabolic and functional markers of Dementia IN Older people" (ODINO) study was conceived as a multi-dimensional investigation in which multi-marker discovery will be coupled with innovative statistical approaches to characterize patterns of systemic inflammation, metabolic perturbations, and physical performance in older adults with MCI. The ultimate aim of ODINO is to identify potential biomarkers specific for MCI subtypes and predictive of MCI conversion into Alzheimer's disease or other forms of dementia over a three-year follow-up. Here, we describe the rationale, design, and methods of ODINO.

Protein-Related Dietary Parameters and Frailty Status in Older Community-Dwellers across Different Frailty Instruments.

The present study investigated the associations between frailty status and (a) daily protein intake, (b) daily body weight-adjusted protein intake, (c) branched-chain amino acid (BCAA) consumption, (d) evenness of protein distribution across main meals, (e) number of daily meals providing at least 30 g of protein, and (f) number of daily meals providing at least 0.4 g protein/kg of body weight in community-dwelling older adults. The relationship between frailty status and protein-related dietary parameters was explored across different frailty assessment tools. Two hundred older adults were enrolled in the study. Participant frailty status was determined according to a modified Fried's frailty phenotype (mFP), the FRAIL scale, and the Study of Osteoporotic Fracture (SOF) index. Diet was assessed by 24-h dietary recall, while diet composition was estimated using a nutritional software. A frailty instrument-dependent relationship was observed between frailty status and protein-related dietary parameters. Protein consumption was associated with frailty status only in participants identified as frail according to the mFP. In addition, protein and BCAA intake was found to be greater in robust and pre-frail participants relative to their frail counterparts. Our findings suggest that the association between frailty and protein-related dietary parameters is tool dependent. Specifically, protein and BCAA consumption appears to be lower only in older adults identified as frail by the mFP.

If my muscle could talk: Myokines as a biomarker of frailty.

Frailty is a potentially reversible state of increased vulnerability to negative health-related outcomes that occurs as a result of multisystem biological impairment and environmental aspects. Given the relevance of this condition in both clinics and research, biomarkers of frailty have been actively sought after. Although several candidate biomarkers of frailty have been identified, none of them has yet been incorporated in the assessment or monitoring of the condition. Over the last years, increasing research interest has been focused on myokines, a set of cytokines, small proteins and proteoglycan peptides that are synthetized, expressed and released by skeletal myocytes in response to muscular contractions. Myokines may act in autocrine, paracrine, and endocrine manner and regulate several processes associated with physical frailty, including muscle wasting, dynapenia, and slowness. This review discusses the rationale to support the use of myokines as biomarkers of frailty in older adults.

High relative consumption of vegetable protein is associated with faster walking speed in well-functioning older adults.

BACKGROUND: Adequate nutrition and, especially, optimal protein intake are necessary to preserve physical function during aging. Increased consumption of animal-derived protein is often advocated as a strategy to support physical performance in old age. However, there is a lack of empirical evidence to support this claim. AIMS: To assess the relationship of protein consumption and specific protein sources with physical function in older adults. METHODS: Participants were community dwellers aged 60 years and older recruited in São Paulo, Brazil. Enrollees had their medical books reviewed and were evaluated for anthropometry, physical performance, and diet. Physical performance was evaluated by isometric handgrip strength and walking speed (WS) tests. Diet was assessed using a 24-h recall diary. RESULTS: Ninety older adults were recruited (mean age: 68.0 ± 6.7 years; 87.0% women). Body weight-adjusted protein consumption was significantly associated with upper-limb muscle strength (r = 0.21; p < 0.05), but not with usual (r = 0.09; p > 0.05) or fast WS (r = 0.08; p > 0.05). Conversely, relative protein consumption was correlated with usual WS (r = 0.13; p < 0.05), while fast WS was negatively associated with relative animal protein intake (r = - 0.18; p < 0.05) and positively associated with relative plant-based protein ingestion (r = 0.15; p < 0.05). DISCUSSION: Findings of the present study indicate that different measures of protein intake are associated with distinct components of physical function. In addition, high relative ingestion of vegetable protein is associated with faster WS. CONCLUSIONS: A comprehensive dietary evaluation is necessary to appreciate the impact of specific nutrients on physical performance in older people. Future interventional studies are needed to establish the optimal blend of protein sources to support physical performance in old age.

Non-periodized and Daily Undulating Periodized Resistance Training on Blood Pressure of Older Women.

The present study aimed at investigating the effects of a daily undulating periodization (DUP) and non-periodized (NP) resistance training programs on hemodynamic parameters of older women. Forty-two older women were randomized into one of the three experimental groups: NP, DUP, and control group (CG). Evaluations of the hemodynamic parameters occurred before, during and after the intervention. The exercise programs were performed twice a week over 22 weeks. NP and DUP groups were based on 3 sets of 8-10 repetitions in 9 exercises. In NP, the two exercise sessions were based on traditional strength training, which was performed at a Difficult intensity according to the rating of perceived exertion (RPE) method. In DUP, the first session was based on power resistance exercise, in which the concentric muscle contraction was performed as fast as possible at a moderate intensity based on RPE, while the second session was the same that was performed by NP. The findings demonstrated that diastolic blood pressure (90.4 vs. 76.2 mmHg) and mean arterial pressure (108.6 vs. 92.7 mmHg) were significantly reduced after NP, while no significant alterations were observed in DUP. Nevertheless, both training groups seem to have a cardio protective effect, since both training modes prevented the increase in HR reported in the experimental period in CG. In conclusion, our findings indicate that a 22-week NP resistance training program causes beneficial effects on hemodynamic parameters of older women. Trial Registration: NCT03443375.

Pyridostigmine Improves the Effects of Resistance Exercise Training after Myocardial Infarction in Rats.

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Exercise training and pharmacological treatments are important strategies to minimize the deleterious effects of MI. However, little is known about the effects of resistance training combined with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on the inflammatory profile after MI. Thus, in the present study, male Wistar rats were randomly assigned into: control (Cont); sedentary infarcted (Inf); PYR - treated sedentary infarcted rats (Inf+P); infarcted rats undergoing resistance exercise training (Inf+RT); and infarcted rats undergoing PYR treatment plus resistance training (Inf+RT+P). After 12 weeks of resistance training (15-20 climbs per session, with a 1-min rest between each climb, at a low to moderate intensity, 5 days a week) and/or PYR treatment (0.14 mg/mL of drink water), hemodynamic function, autonomic modulation, and cytokine expressions were evaluated. We observed that 3 months of PYR treatment, either alone or in combination with exercise, can improve the deleterious effects of MI on left ventricle dimensions and function, baroreflex sensitivity, and autonomic parameters, as well as systemic and tissue inflammatory profile. Furthermore, additional benefits in a maximal load test and anti-inflammatory state of skeletal muscle were found when resistance training was combined with PYR treatment. Thus, our findings suggest that the combination of resistance training and PYR may be a good therapeutic strategy since they promote additional benefits on skeletal muscle anti-inflammatory profile after MI.

Myocardial Infarction and Exercise Training: Evidence from Basic Science.

In 2016, cardiovascular disease remains the first cause of mortality worldwide [1]. Coronary artery disease, which is the most important precursor of myocardial infarction (MI), is the main component of total cardiovascular mortality, being responsible for approximately seven million of deaths [1]. In approximately 20% of infarcted patients, MI is recurrent in the first year after the event [2]. Moreover, among cardiovascular disease, coronary artery disease accounts for the most increased index of life years lost due to morbidity and/or mortality [1]. Sedentarism highly contributes to cardiovascular disease burden, especially for coronary artery disease, and is also one of the MI risk factors [3]. For many years, it was recommended to avoid physical activity after a cardiovascular event; nowadays, it is a consensus that exercise training (ET) should be part of cardiac rehabilitation programs. There is increasing evidence confirming that, when adequately prescribed and supervised, ET after MI can prevent future complications and increase the quality of life and longevity of infarcted patients [4, 5]. ET after MI follows international specialized guidelines; however, there are different protocols adopted by several societies worldwide in cardiac rehabilitation [6], and there is still lack of information on which type and regimen of exercise may be the ideal after MI, as well as how these exercises act to promote beneficial effects to cardiovascular and other organic systems. Thus, experimental studies are important contributors to elicit mechanisms behind clinical results, and to test and compare different ET protocols. Therefore, exercise prescription can be optimized, individualized, and safely practiced by patients. In this chapter, we present a brief review of MI pathophysiology followed by an updated discussion of the most relevant discoveries regarding ET and MI in basic science.