Decline In Grip Strength Research Articles

Sleep Deprivation and Subchronic Arsenite Exposure Synergistically Induced Skeletal Muscle Aging by Disrupting Melatonin and Cortisol Secretion in Mice

In recent years, the influence of environmental factors on organismal aging has garnered increasing attention. Studies have shown that sleep deprivation and environmental pollutants could accelerate the emergence of multiple organismal aging phenotypes. In addition, studies have shown that chronic exposure to sodium arsenite (iAs) induces skeletal muscle atrophy and the inhibition of melatonin secretion in rats. This study aimed to reveal the synergistic effect of sleep deprivation and arsenite exposure on skeletal muscle aging, including reduced limb grip strength and skeletal muscle mass, along with the serum levels of melatonin (MT) and cortisol (COR) in C57BL/6J mice. The results demonstrated that while exposure to arsenite for 12 weeks or sleep deprivation (SD) for 4 weeks did not exert significant effects on limb grip strength or skeletal muscle mass, their combination exhibited a synergistic effect on skeletal muscle aging. Notably, the iAs+SD group exhibited a significant decline in limb grip strength by Week 12, accompanied by a reduced gastrocnemius muscle mass and muscle index. The pathological analysis showed muscle fiber atrophy, a shift towards slow-twitch muscle fibers (type I), and shortened telomere length. Additionally, oxidative damage was increased in the SD and iAs+SD groups, with decreased levels of SOD and GPx and elevated levels of MDA in the iAs+SD group. The serum MT level and MT/COR ratio were significantly reduced, while the serum COR level was elevated in the iAs+SD group compared to the other groups. A correlation analysis further revealed that the serum MT level and the MT/COR ratio were positively correlated with limb grip strength, muscle index, and telomere length, whereas the serum COR level exhibited negative correlations with these parameters. These findings suggest that sleep deprivation and subchronic exposure to arsenite synergistically induce skeletal muscle aging, and that the disruption of the balance between MT and COR potentially serves as a significant risk factor.

Cemdomespib Therapy Slows the Progression of Neuromuscular Weakness and Demyelination in the R75W-Connexin 32 Animal Model of Charcot-Marie-Tooth 1X Disease.

Mutations in connexin 32 (Cx32) are a common cause of Charcot-Marie-Tooth 1X (CMT1X) disease, an inherited peripheral neuropathy characterized by progressive neuromuscular weakness and demyelination. There are no approved pharmacologic therapies for CMT1X, and identifying new treatments that slow the onset and severity of neuromuscular decline may aid disease management. Cemdomespib is an orally bioavailable small molecule that improved demyelination and neuromuscular junction (NMJ) morphology in mice lacking Cx32 expression. However, whether a similar efficacy may manifest in models of CMT1X arising from Cx32 mutations that cause the organellar accumulation of the protein was unclear. Additionally, it was unclear whether cemdomespib therapy slowed the rate of demyelination/NMJ degeneration or stabilized nerve and NMJ morphology to levels present at the initiation of drug therapy. To address these issues, 4-month-old R75W-Cx32 mice, which accumulate the mutant Cx32 in golgi, were treated for 0, 10, or 20 weeks with 0 or 3 mg/kg cemdomespib. Grip strength, motor nerve conduction velocity (MNCV), femoral nerve myelination, and NMJ morphology were quantified. Daily drug therapy significantly slowed the decline in grip strength over the course of treatment, while 20 weeks of drug treatment significantly improved MNCV and decreased the g-ratio and the number of thinly myelinated femoral nerve axons. Similarly, 20 weeks of cemdomespib therapy improved the NMJ morphology and the overlap between presynaptic (synaptophysin) and postsynaptic (α-bungarotoxin) markers. These data show that cemdomespib therapy slows the rate of neuromuscular decline and demyelination and may present a disease-modifying approach for patients with gain-of-function Cx32 mutations.

Change in Grip and Pinch Strength Over the Course of a Game in Professional Baseball Pitchers.

Baseball pitching injuries can be related to fatigue. Changes in grip and pinch strength over the course of professional baseball games are unknown. Grip and pinch strength will decrease as the number of innings pitched increases; injured pitchers will have a lower grip strength than uninjured pitchers. Prospective cohort study. Level 3. Minor league pitchers for 1 affiliate of a single organization were included. Changes in dominant and nondominant grip, and middle and index finger pincer strength were recorded pregame and after each inning, and compared between players who sustained a shoulder/elbow injury and those who did not. Of 41 pitchers included, 6 sustained a shoulder (n = 2) or elbow (n = 4) injury during the study period. Average grip strength for all pitchers was 124.5 ± 17 lb pregame and increased slightly after the first inning (125.2 ± 17 lb), then declined slowly after the second (120.7 ± 18.5 lb), third (119.2 ± 24 lb), and fourth (113.1 ± 19.6 lb) innings. There was a slight uptick in grip strength in the fifth (118.5 ± 23.6 lb) and sixth (121.3 ± 21.8 lb) innings, but pregame levels were not reached. Evaluating uninjured and injured pitchers, the grip strength of injured pitchers was lower at all timepoints. As a percentage of uninjured pitchers grip strength, injured pitcher grip strength was 94.8% pregame, and 97.9%, 95.4%, 81.8%, 87.7%, 82.3%, and 74.5% after the first to sixth innings, respectively. Dominant arm grip strength generally declined over the course of a game in professional baseball pitchers. Injured pitchers generally had weaker grip strength and a steeper decline in grip strength during games compared with uninjured pitchers. Incremental loss of grip strength may increase injury risk in professional baseball pitchers.

Differential effects of EPA and DHA on aging-related sarcopenia in mice and possible mechanisms involved.

Sarcopenia frequently occurs with aging and leads to major adverse impacts in elderly individuals. The protective effects of omega-3 polyunsaturated fatty acids against aging-related sarcopenia have been demonstrated; however, the effect and underlying mechanism of EPA or DHA alone remain inconclusive. Hence, the present study was aimed to clarify the differential effects and possible mechanisms of EPA and DHA on aging-related sarcopenia. In this study, two-month-old and eighteen-month-old male C57BL/6J mice were fed with an AIN-93M diet and an AIN-93M diet containing 1% EPA or 1% DHA for 24 weeks, respectively. The results revealed that EPA and DHA supplementation effectively alleviated the decline in grip strength, skeletal muscle mass, and myofiber cross-sectional areas in aged mice, with EPA exhibiting a better effect against aging-related sarcopenia than DHA. The ROS scavenging role of EPA in aged skeletal muscle was also superior to that of DHA. Additionally, EPA showed a stronger role in improving protein turnover and myogenesis in aged skeletal muscle, as evidenced by suppressing the activation of FoxO3a and NF-κB, blunting the expression levels of muscle atrophy markers MAFbx and MuRF1, activating the PI3K/Akt/mTOR signaling pathway, and elevating MyoD expression. Moreover, EPA also revealed a better effect on inhibiting mitochondria- and endoplasmic reticulum stress-mediated apoptosis in aged skeletal muscle. Furthermore, EPA manifested a more pronounced effect on improving mitochondrial damage of aged skeletal muscle than DHA, and the reason might be due to its superior capability of regulating mitochondrial quality control, as clearly shown by enhancing mitochondrial biogenesis through the AMPK/PGC-1α-dependent pathway, restraining the loss of mitochondrial fusion and fission proteins including Opa1, Mfn2, and Fis1, and promoting mitophagy via the PINK1/Parkin-dependent pathway.

Associations of childhood socioeconomic position and health with trajectories of grip strength from middle to older ages in populations from China and England

BackgroundWe investigated associations of childhood socioeconomic position and health with trajectories of grip strength from middle to older ages in two distinct populations. MethodsWe used data from the China Health and Retirement Longitudinal Study (CHARLS, n = 16,701) and English Longitudinal Study of Ageing (ELSA, n = 12,695). Hand grip strength was measured at three timepoints in CHARLS (2011–2015) and four in ELSA (2001−2020). Random-effects growth models were applied to assess associations between each childhood factor and age trajectories of grip strength. FindingsLower parental education was associated with weaker grip strength, by 0·36 kg(95 % CI:0·17,0·56) for participants of illiterate (vs literate) parents in CHARLS and 1·88 kg(0·43,3·33) for participants of parents without education (vs ≥ high school) in ELSA, after adjusting for parental occupation and own adult socioeconomic position. Low parental occupation was associated with weaker grip strength, although the difference diminished after adjustment for adult socioeconomic position. Financial hardship was associated with weaker grip strength only in CHARLS, by 0·19 kg(0·01,0·38) after adjustment. Self-rated poor childhood health and school absenteeism were associated with weaker grip strength (both studies). Being confined to bed and hospitalised for more than a month due to health were associated with weaker grip strength only in CHARLS. Each additional childhood illness (only reported in ELSA) was associated with 0·52 kg(0·28,0·81) lower mean grip strength. Reported poor childhood health (CHARLS), low parental education and school absenteeism (ELSA) were associated with grip strength decline. InterpretationLower socioeconomic position and poor health in childhood were associated with weaker grip strength in later life in both Chinese and English populations. Addressing socioeconomic disparities and promoting health of children may enhance life-course physical capacity, promote healthy ageing and reduce age-related adversities.

Multi-domain predictors of grip strength differentiate individuals with and without alcohol use disorder.

Grip strength is considered one of the simplest and reliable indices of general health. Although motor ability and strength are commonly affected in people with alcohol use disorder (AUD), factors predictive of grip strength decline in AUD have not been investigated. Here, we employed a data-driven analysis predicting grip strength from measurements in 53 controls and 110 AUD participants, 53 of whom were comorbid with HIV infection. Controls and AUD were matched on sex, age, and body mass index. Measurements included commonly available metrics of brain structure, neuropsychological functioning, behavioural status, haematological and health status, and demographics. Based on 5-fold stratified cross-validation, a machine learning approach predicted grip strength separately for each cohort. The strongest (top 10%) predictors of grip were then tested against grip strength with correlational analysis. Leading grip strength predictors for both cohorts were cerebellar volume and mean corpuscular haemoglobin concentration. Predictors specific to controls were Backwards Digit Span, precentral gyrus volume, diastolic blood pressure, and mean platelet volume, which together significantly predicted grip strength (R2=0.255, p= 0.001). Unique predictors for AUD were comorbidity for HIV infection, social functioning, insular volume, and platelet count, which together significantly predicted grip strength (R2=0.162, p= 0.002). These cohort-specific predictors were doubly dissociated. Salient predictors of grip strength differed by diagnosis with only modest overlap. The constellation of cohort-specific predictive measurements of compromised grip strength provides insight into brain, behavioural, and physiological factors that may signal subtly affected yet treatable processes of physical decline and frailty.

Gasdermin D is activated but does not drive neurodegeneration in SOD1 G93A model of ALS: Implications for targeting pyroptosis.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron loss, microgliosis, and neuroinflammation. While pyroptosis, an inflammatory form of programmed cell death, has been implicated in ALS, the specific role of Gasdermin D (GSDMD) - the primary executioner of pyroptosis - remains unexplored. In this study, we examined the function of GSDMD in the well-established SOD1 G93A mouse model of ALS. Our results showed robust GSDMD activation in the spinal cords of SOD1 G93A animals across two strain backgrounds, with elevated expression in Iba1+ microglia. To explore its role in disease progression, we bred B6.SOD1 G93A mice onto a GSDMD - deficient background. In comparing SOD1 G93A ; Gsdmd +/+ and SOD1 G93A ; Gsdmd -/- mice, we found that Gsdmd loss did not affect disease onset, weight loss, or grip strength decline in either male or female animals. Notably, GSDMD deficiency resulted in a modest but statistically significant increase in mortality in SOD1 G93A mice. Moreover, GSDMD absence had minimal impact on astrogliosis, microgliosis and motor neuron loss. These findings show that while GSDMD is activated in the ALS mouse model, its loss does not mitigate key ALS behavioral phenotypes, gliosis or motor neuron loss. This study provides insights into the potential therapeutic relevance of targeting pyroptosis and inflammatory pathways in ALS.

Low-dose orthotopic cancer implantation permits measurement of longitudinal functional changes associated with cachexia.

Progressive functional decline is a key element of cancer-associated cachexia. Major barriers to translating preclinical therapies into the clinic include lack of cancer models that accurately mimic functional decline, which develops over time, and use of nonspecific measures, like grip strength, as surrogates for physical function. In this study, we aimed to extend the survival and longevity of a cancer model, to investigate cachexia-related function at the basic science level. Survival extension studies were performed by testing multiple cell lines, dilutions, and vehicle-types in orthotopic implantation of K-rasLSL.G12D/+; Trp53R172H/+; Pdx-1-Cre (KPC)-derived cells. One hundred twenty-eight animals in this new model were assessed for cachexia syndrome phenotype using a battery of anatomical, biochemical, and behavioral techniques. We extended the survival of the KPC orthotopic model to 8-9 wk postimplantation using a relatively low 100-cell dose of DT10022 KPC cells (P < 0.001). In this low-dose orthotopic (LO) model, progressive muscle wasting was detected in parallel to systemic inflammation; skeletal muscle atrophy at the fiber level was detected as early as 3 wk postimplantation compared with controls (P < 0.001). Gait speed in LO animals declined as early as 2 wk postimplantation, whereas grip strength change was a late event. Principal component and regression analyses revealed distinct cachectic and noncachectic animal populations, which we leveraged to show that the gait speed decline was specific to cachexia (P < 0.01), whereas grip strength decline was not (P = 0.19). Gait speed represents an accurate surrogate for cachexia-related physical function as opposed to grip strength.NEW & NOTEWORTHY Previous studies of cancer-induced cachexia have been confounded by the relatively rapid death of animal subjects. Using a lower dose of cancer cells in combination with a battery of behavioral, structural, histological, and biochemical techniques, we show that gait speed is actually the best indicator of functional decline due to cachexia. Future studies are required to define the underlying physiological basis of these findings.

Oral Administration of Nacre Extract from Pearl Oyster Shells Has Anti-Aging Effects on Skin and Muscle, and Extends the Lifespan in SAMP8 Mice.

Pearl oysters have been extensively utilized in pearl production; however, most pearl oyster shells are discarded as industrial waste. In a previous study, we demonstrated that the intraperitoneal administration of pearl oyster shell-derived nacre extract (NE) prevented d-galactose-induced brain and skin aging. In this study, we examined the anti-aging effects of orally administered NE in senescence-accelerated mice (SAMP8). Feeding SAMP8 mice NE prevented the development of aging-related characteristics, such as coarse and dull hair, which are commonly observed in aged mice. Additionally, the NE mitigated muscle aging in SAMP8 mice, such as a decline in grip strength. Histological analysis of skeletal muscle revealed that the NE suppressed the expression of aging markers, cyclin-dependent kinase inhibitor 2A (p16) and cyclin-dependent kinase inhibitor 1 (p21), and increased the expression of sirtuin1 and peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1)- α, which are involved in muscle synthesis. These findings suggest that the oral administration of NE suppresses skeletal muscle aging. Moreover, NE administration suppressed skin aging, including a decline in water content. Interestingly, oral administration of NE significantly extended the lifespan of SAMP8 mice, suggesting that its effectiveness as an anti-aging agent of various tissues including skeletal muscle, skin, and adipose tissue.

Initial data analysis for longitudinal studies to build a solid foundation for reproducible analysis.

Initial data analysis (IDA) is the part of the data pipeline that takes place between the end of data retrieval and the beginning of data analysis that addresses the research question. Systematic IDA and clear reporting of the IDA findings is an important step towards reproducible research. A general framework of IDA for observational studies includes data cleaning, data screening, and possible updates of pre-planned statistical analyses. Longitudinal studies, where participants are observed repeatedly over time, pose additional challenges, as they have special features that should be taken into account in the IDA steps before addressing the research question. We propose a systematic approach in longitudinal studies to examine data properties prior to conducting planned statistical analyses. In this paper we focus on the data screening element of IDA, assuming that the research aims are accompanied by an analysis plan, meta-data are well documented, and data cleaning has already been performed. IDA data screening comprises five types of explorations, covering the analysis of participation profiles over time, evaluation of missing data, presentation of univariate and multivariate descriptions, and the depiction of longitudinal aspects. Executing the IDA plan will result in an IDA report to inform data analysts about data properties and possible implications for the analysis plan-another element of the IDA framework. Our framework is illustrated focusing on hand grip strength outcome data from a data collection across several waves in a complex survey. We provide reproducible R code on a public repository, presenting a detailed data screening plan for the investigation of the average rate of age-associated decline of grip strength. With our checklist and reproducible R code we provide data analysts a framework to work with longitudinal data in an informed way, enhancing the reproducibility and validity of their work.

Chronic Astrocytic TNFα Production in the Preoptic-Basal Forebrain Causes Aging-like Sleep-Wake Disturbances in Young Mice.

Sleep disruption is a frequent problem of advancing age, often accompanied by low-grade chronic central and peripheral inflammation. We examined whether chronic neuroinflammation in the preoptic and basal forebrain area (POA-BF), a critical sleep-wake regulatory structure, contributes to this disruption. We developed a targeted viral vector designed to overexpress tumor necrosis factor-alpha (TNFα), specifically in astrocytes (AAV5-GFAP-TNFα-mCherry), and injected it into the POA of young mice to induce heightened neuroinflammation within the POA-BF. Compared to the control (treated with AAV5-GFAP-mCherry), mice with astrocytic TNFα overproduction within the POA-BF exhibited signs of increased microglia activation, indicating a heightened local inflammatory milieu. These mice also exhibited aging-like changes in sleep-wake organization and physical performance, including (a) impaired sleep-wake functions characterized by disruptions in sleep and waking during light and dark phases, respectively, and a reduced ability to compensate for sleep loss; (b) dysfunctional VLPO sleep-active neurons, indicated by fewer neurons expressing c-fos after suvorexant-induced sleep; and (c) compromised physical performance as demonstrated by a decline in grip strength. These findings suggest that inflammation-induced dysfunction of sleep- and wake-regulatory mechanisms within the POA-BF may be a critical component of sleep-wake disturbances in aging.

The Natural Flavanoid Senolytic Fisetin Mitigates Age-Related Changes in Frailty, Grip Strength, and the Skeletal Muscle Transcriptome in Old Mice

Background: Changes in skeletal muscle (SKM) with aging are characterized, in part, by reduced SKM strength and altered gene expression, both of which contribute to increased frailty. The age-related accumulation of excess senescent cells promotes the sequela of SKM aging and contributes to increased frailty. Thus, reducing senescent cell burden represents a promising therapeutic approach to improve SKM function and reduce frailty with aging. Senolytics are compounds that clear excess senescent cells. Currently available synthetic pharmacological senolytic agents harbor poor safety profiles and have low translational application; thus, new approaches are required. Fisetin (FIS) is a natural flavonoid senolytic compound that may fit this need. However, whether FIS supplementation lowers frailty and mitigates the sequela of SKM aging remains unknown. Hypothesis: FIS supplementation in old mice will ameliorate age-related changes in frailty, SKM strength, and senescence-related gene expression in SKM. Methods: We assessed frailty (via a validated frailty index) and SKM strength (via forelimb grip strength) in old (27 mo) male and female C57BL6/N mice following intermittent oral supplementation of either FIS (OFIS, N=39/19 female; 100 mg/kg/day in vehicle [10% EtOH; 30% PEG400; 60% Phosal 50 PG]; 1 week on — 2 weeks off — 1 week on) or vehicle (OC, N=31/13 female). mRNA expression was assessed in isolated quadriceps SKM via bulk RNA sequencing (N=10/group; 5 female). Results were also compared to a young (6 mo) control reference group (YC, N=10; 5 female). Sex differences were not observed, therefore, data were combined for male and female mice. Data are mean ± SEM. Results: Frailty was higher (OC: 0.27 ± 0.01 vs. YC: 0.01 ± 0.004; p&lt;0.05) and grip strength was lower (OC: 2.9g ± 0.01 vs. YC: 4.4g ± 0.02; p&lt;0.05) in old relative to young mice. Pathways associated with cellular senescence were enriched in SKM of OC compared to YC. Some of the most overly expressed genes with aging were related to cellular senescence (e.g., Ankrd1, Gadd45a, Cdkn1a). FIS supplementation reduced the age-related increase in frailty by ~15% (OFIS, 0.23 ± 0.01; p&lt;0.05 vs. OC) and diminished the age-related decline in grip strength by ~30% (OFIS, 3.3g ± 0.1; p&lt;0.05 vs. OC). FIS altered the overall SKM transcriptome in old mice characterized by (1) a less distinct aging phenotype vs. YC analyzed via principal component analysis; and (2) less or no longer enriched cellular senescence-related pathways. A total of six genes were different in OFIS vs. OC (p&lt;0.05; Log 2-fold change ± 0.5). Notably, Adh1 (alcohol dehydrogenase 1; positively associated with longevity) was higher and Ddit4 (DNA damage inducible transcript 4; positively related to DNA damage-induced senescence) was lower. Conclusions: Intermittent oral supplementation with FIS may be an effective therapeutic strategy to treat the sequela of SKM aging and frailty. However, to elicit greater changes in frailty and SKM strength with aging, a stronger or longer FIS dosing paradigm may be required. F32 HL167552; K01 DK115524; AHA 23CDA1056582; F31 HL165885; F31 HL164004; R01 AG055822-S1; K99 HL159241. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Adaptation to full weight-bearing following disuse in rats: The impact of biological sex on musculoskeletal recovery.

With the technological advances made to expand space exploration, astronauts will spend extended amounts of time in space before returning to Earth. This situation of unloading and reloading influences human physiology, and readaptation to full weight-bearing may significantly impact astronauts' health. On Earth, similar situations can be observed in patients who are bedridden or suffer from sport-related injuries. However, our knowledge of male physiology far exceeds our knowledge of female's, which creates an important gap that needs to be addressed to understand the sex-based differences regarding musculoskeletal adaptation to unloading and reloading, necessary to preserve health of both sexes. Using a ground-based model of total unloading for 14 days and reloading at full weight-bearing for 7 days rats, we aimed to compare the musculoskeletal adaptations between males and females. Our results reveal the existence of significant differences. Indeed, males experienced bone loss both during the unloading and the reloading period while females did not. During simulated microgravity, males and females showed comparable muscle deconditioning with a significant decline in rear paw grip strength. However, after 7 days of recovery, muscle strength improved. Additionally, sex-based differences in myofiber size existing at baseline are significantly reduced or eliminated following unloading and recovery.

Biomarkers of Inflammation and Longitudinal Evaluation of Lung Function, Physical Activity, and Grip Strength: A Secondary Analysis in the CASCADE Study.

Physical activity, lung function, and grip strength are associated with exacerbations, hospitalizations, and mortality in people with chronic obstructive pulmonary disease (COPD). We tested whether baseline inflammatory biomarkers were associated with longitudinal outcomes of these physiologic measurements. The COPD Activity: Serotonin Transporter, Cytokines, and Depression (CASCADE) study was a prospective observational study of individuals with COPD. A total of 14 inflammatory biomarkers were measured at baseline. Participants were followed for 2 years. We analyzed associations between baseline biomarkers and forced expiratory volume in 1 second (FEV1), physical activity, and grip strength. We used a hierarchical hypothesis testing procedure to reduce type I error. We used Pearson correlations to test associations between baseline biomarkers and longitudinal changes in the outcomes of interest. We used Fisher's linear discriminant analysis to test if linear combinations of baseline biomarkers predict rapid FEV1 decline. Finally, we used linear mixed modeling to test associations between baseline biomarkers and outcomes of interest at baseline, year 1, and year 2; models were adjusted for age, smoking status, baseline biomarkers, and FEV1. A total of 302 participants (age 67.5 ± 8.5 years, 19.5% female, 28.5% currently smoking) were included. Baseline biomarkers were not associated with longitudinal changes in grip strength, physical activity, or rapid FEV1 decline. Higher interleukin-6 and C-reactive protein were associated with lower physical activity at baseline and these relationships persisted at year 1 and year 2. Baseline inflammatory biomarkers did not predict changes in lung function or physical activity, but higher inflammatory biomarkers were associated with persistently low levels of physical activity.

α-Tocopherol Depletion Exacerbates Lipopolysaccharide-Induced Reduction of Grip Strength

Backgroundα-Tocopherol (αT) deficiency causes several neurologic disorders, such as spinocerebellar ataxia, peripheral neuropathy, and myopathy. Furthermore, decreased antibody production, impaired ex vivo T cell function, and elevated cytokine production are observed in humans and mice with αT deficiency. Although modeling αT deficiency in animals is challenging, αT depletion can be more readily achieved in α-tocopherol transfer protein-null (Ttpa-/-) mice than wild-type (WT) mice. Thus, the Ttpa-/- mouse model is a useful tool for studying metabolic consequences of low αT status. Optimizing this mouse model and selecting the reliable indicators/markers of deficiency are still needed. ObjectiveOur objective was to assess whether αT depletion alters lipopolysaccharide (LPS)-induced inflammatory response in the brain and/or grip strength used as a proxy for fatigue. MethodsWT and Ttpa-/- weanling littermates (n = 37–40/genotype) were fed an αT deficient diet ad libitum for 9 wk. Mice were then injected with LPS (10 μg/mouse) or saline (control) intraperitoneally and killed 4 h later. Concentrations of αT in diet and tissues were measured via high-pressure liquid chromatography. Grip strength was evaluated via a grip strength meter apparatus 2 d before and 3.5 h after LPS injection. Cerebellar and serum interleukin-6 (IL-6) concentrations were measured via enzyme-linked immunosorbent assay. ResultsαT concentrations in the liver, heart, and adipose tissue of WT mice were higher than Ttpa-/- mice. Although αT was detected in the brain, muscle, and serum of WT mice, it was undetectable in these tissues of Ttpa-/- mice. Cerebellar and serum concentrations of IL-6 were increased in LPS-treated groups but were not significantly affected by genotype. Grip strength was reduced in LPS-treated groups, an effect that was more pronounced in Ttpa-/- mice. ConclusionsSystemic LPS administration caused an acute inflammatory response with a concomitant decline in grip strength, especially in Ttpa-/- mice. αT depletion appears to exacerbate reductions in grip strength brought on by systemic inflammation.

SOCIAL ISOLATION AS A RISK FACTOR FOR GRIP STRENGTH DECLINE: FINDINGS FROM THE NHATS STUDY

Abstract Low grip strength is associated with negative health outcomes among older adults, including poor physical performance, sarcopenia, and all-cause mortality. Social isolation has been also linked with decreased physical function and mortality. Limited studies examined whether social isolation is a risk factor for grip strength decline among older adults and whether race differences exist in this association using population-based longitudinal data. The aim of this study was to evaluate the relationship between social isolation and grip strength among older adults and whether the relationship varies by race and over time. We analyzed National Health and Aging Trends Study (NHATS) data (2015 - 2018) and the sample included 4877 adults &amp;gt; 65 years old. Grip strength was measured using a digital hand dynamometer. Social isolation was measured using six NHATS items from the literature and the composite score ranged from 0 to 6, with a higher score indicating more isolation. The sample mean age was 75 (SD = 22; 68 - 110 years). Repeated-measures analysis of variance showed significant differences in grip strength across social isolation scores (p = .001) indicating that socially isolated older adults have significantly lower grip strength. We also found that grip strength significantly decreased by 2.046 kg over the four-year period (p = &amp;lt; .001). The findings showed no significant difference in grip strength across race and change in grip strength across time did not differ by race and social isolation. Interventions to improve muscle strength and reduce social isolation among older adults are needed.

Hand grip strength, anthropometrics and cognitive decline

AbstractBackgroundHand grip strength is a well validated measure of physical strength, while anthropometric measures such as weight, waist, hip and mid upper arm circumference, are well validated to determine physical health. The present analysis investigated the relationship between hand grip strength, anthropometric measures and dementia incidence in 70–90‐year‐old men residing in Northern Ireland (NI).MethodThe PRIME‐COG study is nested in PRIME (Prospective Epidemiological Study of Myocardial Infarction), a cohort study of men in NI. In the most recent follow up for PRIME‐COG, men underwent a comprehensive cognitive assessment from which a consensus diagnosis of normal cognitive function, MCI or dementia was made by experienced clinical researchers. Hand grip strength and anthropometrics measures were also recorded. Logistic regression models were performed to assess the association between hand grip strength and anthropometric measures and cognitive endpoints.ResultThe analysis identified that low hand grip strength was associated with dementia and/or MCI, although this did not reach statistical significance (OR 1.39, p = 0.18). In the anthropometric measures, a significant relationship was observed between hip circumference and dementia and/or MCI at PRIME‐COG follow up (OR 0.93, p = 0.01), whereas BMI was non‐significantly associated (OR 1.22, p = 0.58). The remaining anthropometric measures investigated were not found to hold any significant relationships with the cognitive outcomes.ConclusionWithin a cohort of older men residing in NI, low hand grip strength was associated with a 39% increased risk of dementia or MCI, although this was not statistically significant. In anthropometric measures, hip circumference was found to be significantly negatively associated with a 7% reduced risk of dementia or MCI, while BMI was associated with a 22% increased risk, which again was not of statistical significance. The present study helps further contribute to the evidence base that physical well‐being is associated with cognitive function.

Comparison of the Physical Function Trajectories in Three Birth Cohorts of Chinese Older Adults: A 14-Year Longitudinal Study.

It remains uncertain whether the favorable trend of reduction in physical disabilities has become reversed in the recent-born cohorts of older adults. This study aimed to compare the rate of decline with time in self-reported Instrumental Activity of Daily Living (IADL) difficulties, objective measurement of gait speed and grip strength, in three birth cohorts of Chinese older adults. A prospective cohort study. Four thousand Chinese older adults aged 65 years or above in three birth cohorts (1934-1938, 1929-1933, 1905-1928) were recruited from the community in Hong Kong. Grip strength, gait speed and IADL difficulties were measured between 2001 to 2017. Joint models were used to examine the trajectories of grip strength, gait speed and IADL difficulties over time, and the interaction effect of age-by-cohort (or also age2-by-cohort) was also examined. The recently born cohort (1934 - 1938) had worse grip strength and more IADL difficulties at the same age than the earlier two cohorts (1929 - 1933; 1905 - 1928). Furthermore, the most recently born cohort also followed a more rapid decline longitudinally with a greater decline observed in gait speed, grip strength and IADL difficulties for women whereas a greater decline in grip strength and IADL difficulties for men. The continuous improvement of physical limitations in old age may have halted and there appears to be a reversal of this favourable trend in the recent born cohort of older adults living in Hong Kong.

Prevalence of De-Quervain’s Tenosynovitis in Female Tailors in District Wazirabad

Purpose: De Quervain's tenosynovitis affects the thumb abductors close to the radiostyloid process, causes a painful wrist complaint. When performing particular jobs incorrectly, the wrist and thumb might lead to De Quervain's Tenosynovitis. It is associated with work that necessitates repetitive wrist and thumb motion. Pain, numbness, tingling, burning, stiffness, and exhaustion are a few of the warning signs and symptoms. Complaints include a loss of normal sensation, a restriction in range of motion, and a decline in grip strength. The objective of the study was to determine the prevalence of De-Quervain's Tenosynovitis in female tailors in district Wazirabad.&#x0D; Methodology: Amongst female tailors, a cross-sectional survey was done. Based on the inclusion and exclusion criteria, 289 participants were chosen through convenient sampling technique. The process was described to the study participants. The degree of the pain was evaluated using the Numeric Pain Rating Scale (NPRS), and an assessment of the illness was made using the Finkelstein test. Both hands were put to use for the test. Pain over the abductor pollicis longus and extensor pollicis brevis tendons at the wrist is a sign of a positive diagnosis. The SPSS program was used to examine the data. Data was presented in for of tables and charts.&#x0D; Findings: De-Quervain's Tenosynovitis was present in 43% of the population overall. When the results of the right and left hands were compared, it was discovered that 33% females had right hand had De Quervain's tenosynovitis and 10% had it in both hands. Sixty of the respondents reported experiencing mild pain, 41 women reported moderate pain, and 23 reported severe pain. This study concluded that the prevalence of De-Quervain’s Tenosynovitis in female tailors is low.&#x0D; Recommendations: The study was grounded in the Cumulative Stress Theory, emphasizing repetitive motion's impact on occupational health. Tailors should receive training on ergonomics, use ergonomic tools, and undergo regular wrist health check-ups. Policy makers must set occupational health standards for tailors, ensuring ergonomic tool usage, and mandate periodic health audits in tailoring establishments

Proteomics and β-hydroxybutyrylation Modification Characterization in the Hearts of Naturally Senescent Mice

Aging is widely accepted as an independent risk factor for cardiovascular disease (CVD), which contributes to increasing morbidity and mortality in the elderly population. Lysine β-hydroxybutyrylation (Kbhb) is a novel post-translational modification (PTM), wherein β-hydroxybutyrate is covalently attached to lysine ε-amino groups. Recent studies have revealed that histone Kbhb contributes to tumor progression, diabetic cardiomyopathy progression, and postnatal heart development. However, no studies have yet reported a global analysis of Kbhb proteins in aging hearts or elucidated the mechanisms underlying this modification in the process. Herein, we conducted quantitative proteomics and Kbhb PTM omics to comprehensively elucidate the alterations of global proteome and Kbhb modification in the hearts of aged mice. The results revealed a decline in grip strength and cardiac diastolic function in 22-month-old aged mice compared to 3-month-old young mice. High-throughput liquid chromatogram-mass spectrometry analysis identified 1710 β-hydroxybutyrylated lysine sites in 641 proteins in the cardiac tissue of young and aged mice. Additionally, 183 Kbhb sites identified in 134 proteins exhibited significant differential modification in aged hearts (fold change (FC) > 1.5 or <1/1.5, p < 0.05). Notably, the Kbhb-modified proteins were primarily detected in energy metabolism pathways, such as fatty acid elongation, glyoxylate and dicarboxylate metabolism, tricarboxylic acid cycle, and oxidative phosphorylation. Furthermore, these Kbhb-modified proteins were predominantly localized in the mitochondria. The present study, for the first time, provides a global proteomic profile and Kbhb modification landscape of cardiomyocytes in aged hearts. These findings put forth novel possibilities for treating cardiac aging and aging-related CVDs by reversing abnormal Kbhb modifications.