A multimodal exercise countermeasure prevents the negative impact of head-down tilt bed rest on muscle volume and mitochondrial health in older adults.

Mitochondrial dysfunctions are thought to contribute to muscle atrophy and weakness that develop during ageing and mechanical unloading caused by immobilization, bed rest and microgravity. Older adults are at greater risk of developing muscle and mitochondrial dysfunctions in response to unloading. Although exercise is well known to promote muscle and mitochondrial health, its protective effect during mechanical unloading in older adults remains largely unexplored. Here, we investigated the impact of 14 days of head-down tilt bed rest (HDBR) with and without a multimodal exercise countermeasure in older men and women (55-65 years). Leg muscle volume was assessed using magnetic resonance imaging. Biopsies of the vastus lateralis were performed to assess markers of mitochondrial content, respiration, reactive oxygen species (ROS) production and calcium retention capacity (mCRC). Indices of mitochondrial quality control (MQC), including markers of fusion (MFN1 and 2), fission (Drp1), mitophagy (Parkin) and autophagy (p62 and LC3I and II) were measured using immunoblots. Muscle cross-sections were stained for neural cell adhesion molecule (NCAM, a marker of denervation). HDBR triggered muscle atrophy, decreased mitochondrial content and respiration and increased mitochondrial ROS production. HDBR had no impact on mCRC or MQC markers but increased markers of autophagy and denervation. Exercise prevented the deleterious effects of HDBR on leg muscle volume, mitochondrial ROS production and markers of autophagy and denervation. Exercise also increased mitochondrial content and respiration without altering mCRC and MQC markers. Collectively, our results indicate that an exercise countermeasure that can be performed in bed is effective in protecting muscle and mitochondrial health during HDBR in older adults. KEY POINTS: Conditions associated with muscle unloading, such as immobilization, bed rest or microgravity, result in muscle atrophy and weakness, particularly in older adults. Mitochondrial dysfunctions are thought to contribute to muscle atrophy caused by unloading and ageing. However, whether exercise can counteract the deleterious effects of unloading in older adults remains largely unexplored. Here, we report that older adults exposed to 14 days of head-down tilt bed rest (HDBR) displayed upper leg muscle atrophy, a decrease in mitochondrial content and respiration, an increase in H2O2 emission, and an increase in autophagy and denervation markers. No impact of HDBR on mitochondrial quality control was observed. A multimodal exercise countermeasure prevented the deleterious effects of HDBR on upper leg muscle volume, mitochondrial reactive oxygen species emission, and markers of autophagy and denervation and increased mitochondrial content and respiration. These findings highlight the effectiveness of exercise in promoting muscle and mitochondrial health in older adults undergoing bed rest.

Myths and Methodologies: Understanding the health impact of head down bedrest for the benefit of older adults and astronauts. Study protocol of the Canadian Bedrest Study.

Weightlessness during spaceflight can harm various bodily systems, including bone density, muscle mass, strength and cognitive functions. Exercise appears to somewhat counteract these effects. A terrestrial model for this is head-down bedrest (HDBR), simulating gravity loss. This mirrors challenges faced by older adults in extended bedrest and space environments. The first Canadian study, backed by the Canadian Space Agency, Canadian Institutes of Health Research, and Canadian Frailty Network, aims to explore these issues. The study seeks to: (1) scrutinize the impact of 14-day HDBR on physiological, psychological and neurocognitive systems, and (2) assess the benefits of exercise during HDBR. Eight teams developed distinct protocols, harmonized in three videoconferences, at the McGill University Health Center. Over 26 days, 23 participants aged 55-65 underwent baseline measurements, 14 days of -6° HDBR, and 7 days of recovery. Half did prescribed exercise thrice daily combining resistance and endurance exercise for a total duration of 1 h. Assessments included demographics, cardiorespiratory fitness, bone health, body composition, quality of life, mental health, cognition, muscle health and biomarkers. This study has yielded some published outcomes, with more forthcoming. Findings will enrich our comprehension of HDBR effects, guiding future strategies for astronaut well-being and aiding bedrest-bound older adults. By outlining evidence-based interventions, this research supports both space travellers and those enduring prolonged bedrest.

Impact of 14 Days of Bed Rest in Older Adults and an Exercise Countermeasure on Body Composition, Muscle Strength, and Cardiovascular Function: Canadian Space Agency Standard Measures.

INTRODUCTION: Head-down bed rest (HDBR) has long been used as an analog to microgravity, and it also enables studying the changes occurring with aging. Exercise is the most effective countermeasure for the deleterious effects of inactivity. The aim of this study was to investigate the efficacy of an exercise countermeasure in healthy older participants on attenuating musculoskeletal deconditioning, cardiovascular fitness level, and muscle strength during 14 days of HDBR as part of the standard measures of the Canadian Space Agency. METHODS: Twenty-three participants (12 males and 11 females), aged 55-65 years, were admitted for a 26-day inpatient stay at the McGill University Health Centre. After 5 days of baseline assessment tests, they underwent 14 days of continuous HDBR followed by 7 days of recovery with repeated tests. Participants were randomized to passive physiotherapy or an exercise countermeasure during the HDBR period consisting of 3 sessions per day of either high-intensity interval training (HIIT) or low-intensity cycling or strength exercises for the lower and upper body. Peak aerobic power (V̇O2peak) was determined using indirect calorimetry. Body composition was assessed by dual-energy X-ray absorptiometry, and several muscle group strengths were evaluated using an adjustable chair dynamometer. A vertical jump was used to assess whole-body power output, and a tilt test was used to measure cardiovascular and orthostatic challenges. Additionally, changes in various blood parameters were measured as well as the effects of exercise countermeasure on these measurements. RESULTS: There were no differences at baseline in main characteristics between the control and exercise groups. The exercise group maintained V̇O2peak levels similar to baseline, whereas it decreased in the control group following 14 days of HDBR. Body weight significantly decreased in both groups. Total and leg lean masses decreased in both groups. However, total body fat mass decreased only in the exercise group. Isometric and isokinetic knee extension muscle strength were significantly reduced in both groups. Peak velocity, flight height, and flight time were significantly reduced in both groups with HDBR. CONCLUSION: In this first Canadian HDBR study in older adults, an exercise countermeasure helped maintain aerobic fitness and lean body mass without affecting the reduction of knee extension strength. However, it was ineffective in protecting against orthostatic intolerance. These results support HIIT as a promising approach to preserve astronaut health and functioning during space missions, and to prevent deconditioning as a result of hospitalization in older adults.

Feasibility of an Intradialytic Combined Exercise Program Targeting Older Adults With End-Stage Renal Disease.

Intradialytic exercise is feasible and yields substantial clinical benefits in middle-aged patients. However, evidence is scarce in older hemodialysis patients. OBJECTIVE: To assess the feasibility and clinical benefits of supervised, intradialytic exercise in older patients. METHODS: Multicenter one-arm feasibility study. The main outcome was feasibility (ease of recruitment, dropout rate, adherence, affective valence, and adverse events). The secondary outcomes were physical capacity (five-repetition sit-to-stand, 60-s sit-to-stand tests, and grip strength), quality of life (36-Item Short-Form Health Survey), quality of sleep (Pittsburgh Sleep Quality Index), depressive symptoms (Beck Depression Inventory), and dialysis efficacy (Kt/V and urea reduction ratio). RESULTS: About 79% of the screened patients agreed to participate (n = 25, 73 [66-77] years). The dropout rate was high (32%), but adherence remained high among the participants who completed the study (94%). Improvements were found in the five-repetition sit-to-stand (p < .001), 60-s sit-to-stand tests (p = .028), 36-Item Short-Form Health Survey mental component score (p = .008), depressive symptoms (p = .006), and quality of sleep (p = .035). CONCLUSION: Supervised intradialytic exercise seems safe and beneficial in older patients.

Fat-free mass and glucose homeostasis: is greater fat-free mass an independent predictor of insulin resistance?

BACKGROUND: A greater fat-free mass (FFM) is purported to be associated with protective effects on insulin resistance (IR). However, recent studies suggested negative associations between FFM and IR. OBJECTIVES: (1) To explore the direction of the association between FFM and IR in a large heterogeneous sample after controlling for confounding factors. (2) To determine cut off values of FFM associated with an increased risk of IR. METHODS: Outcome variables were measured in 7044 individuals (48.6% women, 20-79 years; NHANES, 1999-2006): body composition [fat mass (FM), FFM and appendicular FFM (aFFM); DXA], FFM index [FFMI: FFM/height (kg/m2)], appendicular FFMI [aFFM/height (kg/m2)] and insulin resistance (HOMA-IR). Multivariate regression analyses were performed to determine the independent predictors of HOMA-IR in younger (20-49 years) and older (50-79 years) men and women. ROC analyses were used to determine FFM cut-offs to identify a higher risk of insulin resistance (HOMA-IR > 75th percentile). RESULTS: aFFMI was an independent predictor of IR in younger (men: ß = 0.21; women: ß = 0.31; all p ≤ 0.001) and older (men: ß = 0.11; women: ß = 0.37; all p ≤ 0.001) individuals. Thresholds for aFFMI at which the risk of IR was significantly increased were 8.96 and 8.39 kg/m2 in younger and older men, and 7.22 and 6.64 kg/m2 in younger and older women, respectively. CONCLUSION: Independently of age, a greater aFFMI was an independent predictor of IR. These results suggest revisiting how we envision the link between FFM and IR and explore potential mechanisms.

Effect of a mixed-exercise program on physical capacity and sedentary behavior in older adults during cancer treatments.

BACKGROUND: Aging, cancer and its treatment all contribute to increase the risk of deconditioning and sedentary behaviors. Mixed exercise is recognized to counteract the effects of aging and deconditioning as well as improving physical capacity during cancer treatment in adults. AIMS: To determine the impact of a mixed exercise program (MXEP) to improve physical capacity and decrease sedentary behavior time (SBT) in older adults during cancer treatment. METHODS: Fourteen participants (68.8 ± 3.4 years) completed 12 weeks of a mixed exercise program (MEXP) (n = 6) or stretching (n = 8) while they were under cancer treatment. Five tests of the Senior Fitness Test (Chair Stand, 8-Foot Up & Go, Arm Curl, Sit & Reach, 6 min Walk Test), two maximal strength tests (leg press and handgrip) and a Global Physical Capacity Score (GPCS) were used to assess physical capacity. For the amount of SBT (min/day), we used question 1 of the Physical Activity Scale for the Elderly. RESULTS: Both groups presented significant pre- vs post-intervention differences for the Chair Stand, Arm Curl, 6 min Walk Tests and also GPCS. Nevertheless, this difference was significantly greater in the MEXP group only for the Chair Stand Test (4.3 ± 2.2 vs 1.0 ± 1.3 reps; p = 0.01) and the GPCS (4.0 ± 0.6 vs 1.5 ± 2.3 points; p = 0.047). A tend to display a greater decrease in SBT (- 295 ± 241 min/week vs - 11 ± 290 min/week; p = 0.079) was observed in favor of MEXP. CONCLUSION: A 12-week mixed exercise program led to significant improvements in physical capacity and may reduce SBT.

The impact of post-resistance exercise protein consumption on subsequent appetite and daily energy intake of sarcopenic older men: a pilot study.

BACKGROUND: Because of its satiating effect, it has been widely purported that a high-protein beverage may reduce subsequent appetite and food intake in healthy aged individuals, therefore annihilating any supplemental effect. AIMS: The goal of the study was to examine the impact of a post-exercise protein supplement from dairy products in the hours following resistance exercise on subsequent energy intake, sensation of hunger, appetite and satiety in sarcopenic older men. METHODS: A randomized double-blind crossover study with three experimental conditions was performed. Nine sarcopenic older (64 ± 3 years) men participated in three experimental conditions: post-exercise protein supplementation made from (1) cow's milk (13 g of proteins); (2) rice milk (isocaloric protein-free beverage) and (3) water (control). Subsequent energy intake was measured with a test buffet and a food record over the rest of the day. Assessment of appetite, satiety and hunger were obtained by visual analogue scales at various times before and after the buffet. RESULTS: Appetite, feeling of hunger and satiety and subsequent energy intake were not significantly different between the three experimental conditions. However, when participants were supplemented with cow's milk, total fat intake during the day of the intervention was significantly lower than with other supplements (p ≤ 0.05). CONCLUSION: Post-exercise consumption of protein supplements made from dairy products appear not to compromise daily nutritional behavior and does not confer the anticipated negative impact on nutritional intake in sarcopenic older men.

Women, weight, poverty and menopause: understanding health practices in a context of chronic disease prevention.

Socioeconomic inequalities in health persist despite major investments in illness prevention campaigns and universal healthcare systems. In this context, the increased risks of chronic diseases of specific sub-groups of vulnerable populations should be further investigated. The objective of this qualitative study is to examine the interaction between socioeconomic status (SES) and body weight in order to understand underprivileged women's increased vulnerability to chronic diseases after menopause. By drawing specifically on Pierre Bourdieu's sociocultural theory of practice, 20 semi-structured interviews were conducted from May to December of 2013 to investigate the health practices of clinically overweight, postmenopausal women living an underprivileged life in Canada. Findings emphasise that poor life conditions undermine personal investment in preventive health and weight loss, showing the importance for policy makers to bring stronger consideration on upstream determinants of health.

Lifestyle Inequalities: Explaining Socioeconomic Differences in Preventive Practices of Clinically Overweight Women After Menopause.

Excess weight and menopause are two major factors increasing aging women's vulnerability to chronic diseases. However, social position and socioeconomic status have also been identified as major determinants influencing both health behaviors and the development of such diseases. This study focuses on the socioeconomic variations of behavioral risk factors of chronic diseases in aging women. By drawing on Bourdieu's sociocultural theory of practice, 40 semistructured interviews were conducted to investigate preventive health practices of clinically overweight, postmenopausal women from contrasting socioeconomic classes living in Canada. Findings emphasize class-based differences with respect to long-term health and preventive practices according to three major themes: priority to long-term time horizons, attention given to risk factors of diseases, and control over future health. Health care providers should strive to work in concert with all subgroups of women to better understand their values, worldviews, and needs to decrease health inequalities after menopause.

Relationships between physical activity across lifetime and health outcomes in older adults: Results from the NuAge cohort.

This study aims to (1) describe participation in four physical activity (PA) domains across life and (2) examine the influence of PA during adolescence, early, middle, and later adulthood on health variables at older age. This observational study was conducted in 1378 generally healthy older adults (age 67-84 at baseline in 2003-2005; 52% women) in Quebec, Canada. Using a modified version of the interviewer-administered Lifetime Total Physical Activity Questionnaire (LTPAQ) and life events calendar to facilitate the recall, participants reported the frequency, duration, and intensity of occupational (OPA), commuting (CPA), household (HPA), and leisure time (LTPA) they participated in at age 15, 25, 45, and 65, and at the first follow-up (age 68-85 in 2005-2006). Fat mass, lean body mass, body mass index, waist-to-hip ratio, fasting glucose, systolic and diastolic blood pressures, self-reported chronic diseases, and socio-demographic data were assessed at baseline. Changes in PA over time differed by sex in each domain. However, there was a general decline in all PA domains in both sexes after age 65. In multiple regression analyses, LTPA at first-follow-up was associated with more favourable waist-to-hip ratio in both sexes, fat mass in women and fat mass percentage in men, whereas CPA, OPA, and HPA across life were not consistently associated with health variables. Older adults' LTPA at first follow-up was related to health variables, but PA recalled during adolescence, early adulthood, and mid-life was not. Results support the idea that current PA is positively related to better health outcomes.

Sixteen weeks of resistance training decrease plasma heat shock protein 72 (eHSP72) and increase muscle mass without affecting high sensitivity inflammatory markers' levels in sarcopenic men.

BACKGROUND: Sarcopenia has been associated with increased systemic inflammation and risk of physical disability in older adults. Recently, extracellular heat shock protein 72 (eHSP72) was proposed as a biomarker of sarcopenia but its response to interventions designed to increase muscle mass has never been evaluated. AIMS: The present study was designed to (1) assess eHSP72 levels following resistance training and, (2) determine whether changes in eHSP72 correlate to changes in muscle mass and inflammatory markers. METHODS: A total of 26 sarcopenic men participated in a 16-week resistance training program. The following variables were measured pre-post-intervention: plasma HSP72, serum high sensitivity (hs) inflammatory markers: interleukin-6 (hsIL-6), C-reactive protein (hsCRP), and tumor necrosis factor alpha (hsTNF-α), lean body mass (LBM) and appendicular muscle mass index (appMMI). RESULTS: eHSP72 was detected in 47 % of our participants and its level significantly decreased (P = 0.04) after the intervention, with a concomitant increase in several LBM variables and appMMI (all P < 0.035). Serum hsIL-6, hsCRP and hsTNF-α changes did not reach significance. Baseline hsIL-6 and hsCRP levels were negatively correlated with several LBM variables but solely baseline hsIL-6 was associated with changes in appLBM. No correlations were found between changes in measured variables. DISCUSSION: Attenuation of eHSP72 following resistance training in parallel with increase in LBM variables showed a concordance between the evolution of this biomarker and a clinical outcome relevant to sarcopenia. CONCLUSION: Nevertheless, the low bloodstream detection rate of eHSP72 in a sarcopenic otherwise healthy population might limit its use in clinical settings for now.

Inflammation and Fat Mass as Determinants of Changes in Physical Capacity and Mobility in Older Adults Displaying A Large Variability in Body Composition: The NuAge Study.

Background/Study context: Determining whether C-reactive protein (CRP), blood lipids, total and trunk fat mass (FM), and waist circumference (WC) are associated with changes in physical capacity over 3 years (Δ) in elderly. METHODS: One hundred twenty-two men and women 68-83 years of age participated in a 3-year follow-up study. Physical capacity was measured using five objective tests: (1) Timed Up and Go (TUG), (2) chair stand (CS), (3) normal walking speed (NWS), (4) fast walking speed (FWS), and (5) one-leg stand (LS), along with physical performance score (PPS) at baseline (T1) and 3 years later (T4). Total and trunk FM, WC, blood lipids, and CRP measured at baseline, were considered as potential predictors. RESULTS: At baseline, CRP and total FM were significantly correlated with all physical capacity tests, whereas trunk FM was correlated with CS and LS, and blood lipids only with FSW. No significant correlation was observed for WC. Total and trunk FM measured at baseline were correlated with ΔTUG and ΔPPS, whereas trunk FM and WC measured at baseline were correlated with ΔNWS. CRP and blood lipids, measured at baseline, were not associated with any changes over 3 years. At the end, WC measured at baseline was the strongest independent predictor for all physical capacity measures at baseline (T1), and ΔPPS measured over 3 years could be predicted by baseline WC. CONCLUSION: FM distribution seems more useful to determine physical capacity than inflammation. Interestingly, over a short follow-up of 3 years, WC significantly predicted changes in a composite score of physical activity. More studies are needed to elucidate factors that may influence physical capacity decline over time.

Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study.

The decrease in resting energy expenditure (REE) and fat oxidation with aging is associated with an increase in fat mass (FM), and both could be prevented by exercise such as resistance training. Dairy consumption has also been shown to promote FM loss in different subpopulations and to be positively associated with fat oxidation. Therefore, we sought to determine whether resistance exercise combined with dairy supplementation could have an additive impact on FM and energy metabolism, especially in individuals with a deficit in muscle mass. Twenty-six older overweight sarcopenic men (65 ± 5 years old) were recruited for the study. They participated in 4 months of resistance exercise and were randomized into three groups for postexercise shakes (control, dairy, and nondairy isocaloric and isoprotein supplement with 375 ml and ~280 calories per shake). Body composition was measured by dual X-ray absorptiometry and REE by indirect calorimetry. Fasting glucose, insulin, leptin, inflammatory profile, and blood lipid profile were also measured. Significant decreases were observed with FM only in the dairy supplement group; no changes were observed for any other variables. To conclude, FM may decrease without changes in metabolic parameters during resistance training and dairy supplementation with no caloric restriction without having any impact on metabolic properties. More studies are warranted to explain this significant decrease in FM.

Effect of Resistance Training and Various Sources of Protein Supplementation on Body Fat Mass and Metabolic Profile in Sarcopenic Overweight Older Adult Men: A Pilot Study.

The decrease in resting energy expenditure (REE) and fat oxidation with aging is associated with an increase in fat mass (FM), and both could be prevented by exercise such as resistance training. Dairy consumption has also been shown to promote FM loss in different subpopulations and to be positively associated with fat oxidation. Therefore, we sought to determine whether resistance exercise combined with dairy supplementation could have an additive impact on FM and energy metabolism, especially in individuals with a deficit in muscle mass. Twenty-six older overweight sarcopenic men (65 ± 5 years old) were recruited for the study. They participated in 4 months of resistance exercise and were randomized into three groups for postexercise shakes (control, dairy, and nondairy isocaloric and isoprotein supplement with 375 ml and ~280 calories per shake). Body composition was measured by dual X-ray absorptiometry and REE by indirect calorimetry. Fasting glucose, insulin, leptin, inflammatory profile, and blood lipid profile were also measured. Significant decreases were observed with FM only in the dairy supplement group; no changes were observed for any other variables. To conclude, FM may decrease without changes in metabolic parameters during resistance training and dairy supplementation with no caloric restriction without having any impact on metabolic properties. More studies are warranted to explain this significant decrease in FM.

Physiological Responses to Indoor Versus Outdoor Training in Postmenopausal Women.

Chronic effects of two different exercise environments on self-chosen intensity and physiological adaptations were examined in postmenopausal women. Twenty-three healthy to overweight (body mass index [BMI] 22-29 kg/m2) postmenopausal women performed three weekly training sessions during 12 weeks and were assigned to either: (1) indoor training or (2) outdoor training. Body composition, metabolic profile, and physical fitness (including Vo2max, maximal strength, and endurance) were assessed pre- and postintervention. Exercise intensity was measured every week during the training. Maximum intensity decreased significantly in time only in outdoor training (p ≤ .05). Body composition and VO2max were significantly improved indoors (p ≤ .05), whereas resting blood pressure and upper body maximal strength and endurance were improved outdoors (p ≤ .05). Indoor training is associated with maintaining intensity over time and slightly higher physiological improvements than outdoor training. However, outdoor training seems promising from a long-term perspective, due to its positive effects on health parameters and exercise adherence.

The Effect of Resistance Training and Different Sources of Postexercise Protein Supplementation on Muscle Mass and Physical Capacity in Sarcopenic Elderly Men.

The loss of muscle mass (sarcopenia) with aging is related to a progressive loss of muscle strength and physical capacity. Resistance exercise and milk-based protein supplementation have been demonstrated as significant countermeasures for sarcopenia and the loss of muscle strength. However, using high doses of proteins can act as a meal replacement in the elderly. Therefore, we sought to determine whether a standard supplementation (12 g per serving) of protein and resistance training could be an efficient strategy to promote muscle strength and physical capacity in sarcopenic men. Twenty-six participants were randomized in 3 groups in a double-blind control study. All the groups performed exercise and consumed a protein-rich supplement 12 g of protein, 7 g of essential amino acids from milk (n = 8), soy (n = 8), or rice milk (nonprotein control, n = 10). Body composition was measured using dual-energy x-ray absorptiometry. Strength was measured by 1 repetition maximum with different exercises. Different physical capacity measurements were assessed (timed up and go test, chair stand, and walking speed). The results indicated a significant increase in fat-free mass in all groups and changes in muscle strength, with no differences between groups. This study indicates that resistance training is an effective way to increase muscle mass and strength, regardless of protein supplementation. Higher doses of protein-rich foods may have to be recommended to promote muscle mass gains when executing resistance exercise in elderly sarcopenic individuals.

Cross-sectional and prospective associations between homocysteine and a frailty index: A post-hoc analysis of the multidomain Alzheimer's prevention trial (MAPT).

BACKGROUND: Homocysteine (Hcy) has been associated with several health problems, including reduced physical capacity. No study appears to have looked at the role of Hcy values longitudinally on physical capacity deterioration in older adults. The objective is to examine cross-sectional and prospective associations between Hcy values and frailty in the elderly and investigate Hcy potential association with the onset of frailty. METHODS: 769 community-dwelling older adults from the MAPT study were recruited for this study. Total Hcy was measured at baseline. Frailty was evaluated at 5 different collection timepoints: baseline, 6-month, 1-, 2-, and 3-year using a frailty index (FI) composed of 19 items. Linear regressions adjusted for all the confounders (age, gender, educational level, MAPT group allocation and Omega-3) were performed to examine the cross-sectional associations of homocysteine values with the FI. A cox model was used to test the association of Hcy with the onset of frailty. RESULTS: Mean Hcy values (15.9 ± 5.6 µmol\L) were obtained from 769 community-dwelling adults (75.7 ± 4.6 years old). After adjustments, a significant (ß = 0.002, (00002-0.003)) and positive association between baseline Hcy values and FI was found (ß = 0.002). Additionally, higher values of Hcy were associated with a worsening of FI after 3 years (ß = 0.002, p = 0.003). A significant association between baseline Hcy values and the likelihood of developing frailty was discovered by incident event analysis (HR: 1.04 (1.01-1.06), p = 0.004). CONCLUSION: High levels of Hcy are associated with the fragility process in community-dwelling older adults.

SARS-CoV-2 spike antigen-specific B cell and antibody responses in pre-vaccination period COVID-19 convalescent males and females with or without post-covid condition.

Background: Following SARS-CoV-2 infection a significant proportion of convalescent individuals develop the post-COVID condition (PCC) that is characterized by wide spectrum of symptoms encompassing various organs. Even though the underlying pathophysiology of PCC is not known, detection of viral transcripts and antigens in tissues other than lungs raise the possibility that PCC may be a consequence of aberrant immune response to the viral antigens. To test this hypothesis, we evaluated B cell and antibody responses to the SARS-CoV-2 antigens in PCC patients who experienced mild COVID-19 disease during the pre-vaccination period of COVID-19 pandemic. Methods: The study subjects included unvaccinated male and female subjects who developed PCC or not (No-PCC) after clearing RT-PCR confirmed mild COVID-19 infection. SARS-CoV-2 D614G and omicron RBD specific B cell subsets in peripheral circulation were assessed by flow cytometry. IgG, IgG3 and IgA antibody titers toward RBD, spike and nucleocapsid antigens in the plasma were evaluated by ELISA. Results: The frequency of the B cells specific to D614G-RBD were comparable in convalescent groups with and without PCC in both males and females. Notably, in females with PCC, the anti-D614G RBD specific double negative (IgD-CD27-) B cells showed significant correlation with the number of symptoms at acute of infection. Anti-spike antibody responses were also higher at 3 months post-infection in females who developed PCC, but not in the male PCC group. On the other hand, the male PCC group also showed consistently high anti-RBD IgG responses compared to all other groups. Conclusions: The antibody responses to the spike protein, but not the anti-RBD B cell responses diverge between convalescent males and females who develop PCC. Our findings also suggest that sex-related factors may also be involved in the development of PCC via modulating antibody responses to the SARS-CoV-2 antigens.