As the elderly population grows, the number of patients with metabolic bone diseases such as osteoporosis has increased sharply, posing a significant threat to public health and social economics. Although pharmacological therapies for osteoporosis demonstrate therapeutic benefits, their prolonged use is associated with varying degrees of adverse effects. As a non-pharmacological intervention, exercise is widely recognized for its cost-effectiveness, safety, and lack of toxic side effects, making it a recommended treatment for osteoporosis prevention and management. Previous studies have demonstrated that exercise can improve metabolic bone diseases by modulating the Senescent Associated Secretory Phenotype (SASP). However, the mechanisms through which exercise influences SASP remain unclear. Therefore, this review aims to summarize the effects of exercise on SASP and elucidate the specific mechanisms by which exercise regulates SASP to alleviate osteoporosis, providing a theoretical basis for osteoporosis through exercise and developing targeted therapies.

This study investigated associations between markers of inflammatory status and adiposity (interleukin-6 [IL-6], adiponectin and leptin) and measures of bone phenotype and fractures. The Medical Research Council (MRC) National Survey of Health and Development (NSHD) is a British birth cohort study. Participants (born during the same week in 1946) with complete data on DXA and pQCT parameters, markers of inflammatory status and adiposity, and potential confounders (498 men and 474 women) were included in cross-sectional analyses. At age 60-64 years, bone phenotype was assessed by DXA and pQCT. Fractures were self-reported at ages 60-64 and 68-70 years. Multiple linear regression was used to determine associations of IL-6, adiponectin and leptin with bone phenotype (adjusted for fat and lean mass and lifestyle confounders). Standard deviation (SD) differences in outcomes per SD increases in exposures were estimated. Higher IL-6 levels were associated with lower total volumetric bone mineral density (vBMD) (- 0.10[- 0.19, 0.00]) in men, and higher areal BMD (aBMD) at the spine (0.12[0.03, 0.22]) and whole body (0.11[0.01, 0.20]) in women. Higher levels of adiponectin were associated with lower aBMD and trabecular vBMD. In women, higher leptin levels were associated with higher cortical vBMD (0.11[0.02, 0.20]). Higher adiponectin was associated with moderately increased odds of having a fragility fracture during adulthood in women (OR 1.16 [95% CI 0.94, 1.43, p = 0.18]). Our results highlight non-mechanical associations between markers of inflammatory status and adiposity with BMD and, in women, fractures. Ensuring inflammaging is minimised may be important in healthy bone ageing.

Nutritional status and levels of oxidative stress may be modifiable risk factors for the development of sarcopenia. The Oxidative Balance Score (OBS) is a comprehensive measure of oxidative balance in diet and life exposures. We conducted a cross-sectional study to investigate the association between OBS and sarcopenia in US adults.

Based on the 2011-2018 National Health and Nutrition Examination Survey (NHANES), this study included 3084 participants. Weighted logistic regression analysis and restricted cubic spline regression (RCS) were used to assess the association between OBS and sarcopenia, as well as gender differences in this association.

OBS and sarcopenia are negatively associated (OR = 0.951, 0.919-0.983, p = 0.004). Compared with the lowest quartile of OBS, the highest quartile was significantly negatively associated with sarcopenia (OR = 0.431, 0.202-0.917, p for trend = 0.01). Both dietary OBS and lifestyle OBS were significantly negatively associated with sarcopenia (OR = 0.963, 0.930-0.997, p = 0.032; OR = 0.634, 0.562-0.715, p < 0.001). In gender subgroup analysis, a significant negative association between OBS and sarcopenia was observed in women (OR = 0.916, 0.862-0.973, p = 0.005), while the association was not significant in men. The RCS showed a significant linear correlation between total population OBS, female OBS and sarcopenia (p for nonlinear >0.05, p for overall <0.05).

Higher oxidative balance scores are associated with a lower prevalence of sarcopenia, particularly among women. These findings support the importance of antioxidant-rich diets and healthy lifestyles in mitigating sarcopenia risk, especially in aging female populations.

Cognitive impairment, dementia and sarcopenia significantly reduce the quality of life in middle-aged and older adults by impairing daily functioning, making cognitive decline a major concern for healthcare professionals.

To estimate the prevalence of sarcopenia and probable sarcopenia in middle-aged and older adults with cognitive impairment.

Six databases-Embase, Ovid MEDLINE, PubMed, CINAHL, Scopus and Web of Science was conducted through February 2025. Cohort and cross-sectional studies included, and a random-effects model was used for pooled prevalence analysis. Cognitive impairment is a decline in cognitive functions, including memory, attention and executive function, covering mild cognitive impairment and dementia. Sarcopenia is decreased skeletal muscle mass and function, assessed by muscle strength or physical performance.

A total of 67 studies involving 23 532 participants revealed a pooled sarcopenia prevalence of 30.1% and a probable sarcopenia prevalence of 40.5%. Additionally, amongst adults aged 65 and older, the prevalence of sarcopenia was 32.7%. The prevalence of sarcopenia varied by setting: 25.3% in community-dwelling populations, 35.5% in hospitals and 41.5% in institutional settings. Moderating factors included age, female, body mass index, comorbidities and risk factors such as depression, diabetes, hypertension, malnutrition, osteoarthritis, alcohol consumption and smoking.

Approximately one-third of middle-aged and older adults with cognitive impairment demonstrate to have sarcopenia. Early detection and tailored interventions by public health professionals are crucial, particularly for individuals with mild cognitive impairment and dementia. Enhanced preventive strategies are essential to improving outcomes and reducing healthcare costs.

The menopause transition is a critical period marked by significant physiological adaptations. Data on the dynamic changes in body composition and metabolism during this transition are limited. The purpose was to determine body composition and metabolic changes over a 2-year follow-up in a cross-sectional sample of premenopausal (PRE), perimenopausal (PERI), and postmenopausal (POST) females.

Twenty-three females who previously participated in a cross-sectional study returned for a 2-year follow-up visit were classified as PRE, PERI, or POST based on menstrual history and a Menopause Health Questionnaire. Muscle size [muscle cross-sectional area (mCSA)] and muscle quality [echo intensity, (EI)] were evaluated in the vastus lateralis with ultrasound. Bone mass and body composition were assessed using dual-energy X-ray absorptiometry, and metabolic flexibility through submax exercise with indirect calorimetry.

At the 2-year follow-up, POST females had an increase in EI (change: 26.93 ± 12.82 a.u., group×time p-adjusted = 0.001) with no change in mCSA (change: -2.03 ± 2.40 cm², group×time p = 0.980). PERI compared to PRE females had lower total bone mass (group×time p-adjusted = 0.029) with an even lower bone mass in POST compared to PERI females (group×time p-adjusted = 0.023). No differences in metabolic flexibility at any exercise intensity were observed between groups over time (group×time p = ≥ 0.05).

This study highlights a decline in muscle quality and total bone mass despite stable muscle size, emphasizing the need for targeted exercise and nutrition interventions to support muscle and bone health in females around the menopause transition.

The benefits of physical exercise are well-known, but there is limited research on its effects on the physical and mental health of elderly individuals with gait disorders. This review aims to evaluate the impact of physical exercise on these outcomes. A literature search was conducted, retrieving studies published from inception to November 2024 in databases such as PubMed, Scopus, Web of Science, ProQuest, and SPORTDiscus. Fifteen randomized controlled trials (RCTs) were included in the review. The results indicate that physical exercise improves both physical health (gait, balance, mobility, reduce fall rate) and mental health (Qality of life [QoL] cognitive function, anxiety levels, and Activities-Specific Balance Confidence [ABC]) in older adults with gait disorders. Of the 15 studies, 10 reported positive effects on both physical and mental outcomes, while the remaining five studies showed either no effect or a lack of positive results. The interventions evaluated included Tai Chi (TC), Tango, aerobic training (AT), resistance training (RT), combined training (CT), virtual reality (VR), resistance training plus standard pharmacological treatment (RTG + pharmacological treatment), high-speed treadmill training, brisk walking, and multimodal exercise program (MEP). Notably, there are six items of TC intervention. Most interventions lasted for 12 weeks with sessions conducted twice a week, each lasting between 30 and 60 minutes. Additionally, limited studies (one per indicator) assessed strength, functional gait assessment (FGA), and center of pressure (COP), indicating a need for more research in these areas. This review concludes that physical exercise is effective in improving physical and mental health outcomes in older adults with gait disorders, with TC emerging as the most commonly used and beneficial intervention.

Background: Osteosarcopenia, the coexistence of osteoporosis and sarcopenia, poses significant challenges in aging populations due to its dual impact on bone and muscle health. Inflammation, mediated by specific cytokines, is thought to play a crucial role in the development of osteosarcopenia, though the underlying mechanisms are not fully understood. Objective: This study aimed to clarify the causal role of circulating cytokines in the pathogenesis of osteosarcopenia by employing mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to identify cell-specific cytokine expression patterns. The ultimate objective was to uncover potential pathological mechanisms and therapeutic targets for treating osteosarcopenia. Methods: A two-sample MR approach was employed, leveraging publicly available genome-wide association study (GWAS) data from multiple cohorts. A total of 91 circulating cytokines were examined using genetic instruments, and their causal effects on traits related to osteoporosis and sarcopenia were evaluated. Various complementary and sensitivity analyses were performed to ensure robust findings. Additionally, scRNA-seq datasets from human muscle and bone marrow were analyzed to validate the single-cell expression profiles of candidate cytokines. Results: MR analysis identified several cytokines with causal effects on osteosarcopenia traits, including LTA, CD40, CXCL6, CXCL10, DNER (delta and notch-like epidermal growth factor-related receptor), and VEGFA (vascular endothelial growth factor A). LTA and CD40 were protective for both bone and muscle, while VEGFA posed a risk. Other cytokines demonstrated opposite effects on bone and muscle. Single cell analysis revealed distinct expression patterns, with LTA highly expressed in lymphocytes, CD40 in immune cells, and VEGFA in various musculoskeletal cell types. Age-related differences in cytokine expression were also noted, with LTA more highly expressed in younger individuals, and VEGFA in older individuals. Conclusion: This study offers preliminary insights into the inflammatory mechanisms potentially driving osteosarcopenia, identifying key cytokines that may be involved in its pathogenesis. By integrating MR and scRNA-seq data, we highlight potential therapeutic targets, though further research is needed to confirm these findings and their implications for musculoskeletal health.

Healthy ageing relies on maintaining physiological systems, particularly the musculoskeletal system (MKS). After 50, declines in bone density, muscle mass and strength increase the risk of osteoporosis and sarcopenia, leading to frailty, fractures and higher healthcare costs. Osteosarcopenia, combining osteoporosis and sarcopenia, is rising because of the ageing population. Chronic kidney disease (CKD) exacerbates this condition through disruptions in mineral metabolism, hormonal imbalances and inflammation, further compromising musculoskeletal health.

This review examines the pathophysiology of osteosarcopenia associated with CKD, focusing on the role of mineral and hormonal disturbances, chronic inflammation and endocrine dysfunction. It aims to increase clinical awareness and highlight the need for early diagnosis and intervention to mitigate the burden of osteosarcopenia on the quality of life and healthcare systems in ageing CKD populations.

A narrative review of the current literature was conducted, summarising evidence on the mechanisms underlying osteosarcopenia in CKD, including mineral metabolism alterations, inflammatory processes and hormonal imbalances.

Osteosarcopenia is a recognised consequence of CKD, contributing to increased morbidity and mortality. The pathophysiology of osteosarcopenia in CKD is multifactorial, involving disruptions in mineral metabolism, inflammation, endocrine dysfunction and physical inactivity. CKD-mineral and bone disorder (CKD-MBD) leads to alterations in calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23) and vitamin D metabolism, resulting in impaired bone mineralisation and increased fracture risk. Simultaneously, CKD accelerates muscle wasting through systemic inflammation, anabolic resistance and metabolic derangements, increasing the risk of sarcopenia. Sarcopenic obesity, inflammaging and hormonal dysregulation further exacerbate bone muscle deterioration. Emerging evidence suggests that osteosarcopenia in CKD is a consequence of interconnected pathophysiological pathways rather than isolated conditions. Diagnosis remains challenging because of overlapping clinical features, necessitating integrated assessment tools. Targeted therapeutic strategies, including mineral metabolism correction, resistance exercise and anabolic interventions, are essential to mitigate osteosarcopenia's progression and improve patient outcomes in CKD.

Osteosarcopenia is a growing concern in ageing CKD populations. Early diagnostic strategies and targeted interventions are essential to mitigate the impact of osteosarcopenia on patient outcomes and reduce associated healthcare costs. Increased clinical awareness and research into effective therapies are crucial for improving the quality of life for individuals affected by CKD and osteosarcopenia.

Exercise is a highly recommended nonpharmacological intervention for older adults with sarcopenia. Poor exercise adherence is a main factor affecting treatment efficacy. However, evidence for overall adherence to exercise and intervention characteristics affecting adherence in this population remains unknown.

To determine whether community-dwelling older adults with sarcopenia adhere to exercise programmes, what intervention components are used to improve adherence and how adherence relates to intervention characteristics and efficacy.

Seven electronic databases and relevant systematic reviews were searched to identify randomised controlled trials (RCTs). The capability, opportunity, motivation and behaviour model with behaviour change techniques (BCTs) were used to categorise adherence intervention components. Random-effects meta-analysis and meta-regression analyses were employed.

Seventeen RCTs with 2975 participants were included in this review. The pooled estimate of adherence rates for exercise interventions amongst older adults with sarcopenia was 85% (95% CI: 0.79-0.89, range: 71%-100%). Nine BCTs were identified from the included studies. Exercise with programme durations (<24 weeks) (P = 0.01) might be associated with higher adherence rates compared with programme durations (≥24 weeks). However, exercise adherence was not associated with intervention efficacy.

Adherence to exercise interventions in community-dwelling older adults with sarcopenia is relatively high and may be affected by programme duration. Most studies incorporated only a small number of BCTs into their exercise interventions. Such an approach may be insufficient to enhance adherence in this population effectively. Future studies with theory-informed interventions to improve adherence in the field of exercise for older people with sarcopenia are needed.

Regular exercise positively influences bone health, enhances bone density and strength, and reduces the risk of osteoporosis. Silent information regulator of transcription 1 (SIRT1) is a deacetylase that plays a pivotal role in the regulation of various biological processes. In this review, we explore the role of SIRT1 in modulating bone metabolism in response to exercise. SIRT1 regulates crucial cellular processes, including inflammation, aging, autophagy, and oxidative stress, in bone cells such as bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts, in response to exercise-induced stimuli. Notably, exercise influences bone metabolism by modulating muscle metabolism and neurotransmitters, with SIRT1 acting as a key mediator. A comprehensive understanding of SIRT1's regulatory mechanisms will facilitate a deeper exploration of the principles underlying exercise-induced improvements in bone metabolism, ultimately providing novel insights into the treatment of bone metabolic disorders.

BackgroundLow bone mineral density (LBMD) significantly contributes to loss of independence, gait impairment, and increased fall risk. Instrumental gait analysis provides an accurate evaluation of walking ability, that represent the first step for a personalized rehabilitation.ObjectiveTo collect and describe the available literature on the effect of LBMD on walking characteristics and the use of motion analysis systems in patients with LBMD.MethodsWe performed a literature search of the last ten years on PubMed, Web of Science and Scopus of papers on older people and patients with LBMD in terms of gait parameters, balance, and fall risk. The review protocol was registered on PROSPERO (CRD42024590090).ResultsThe database search identified totally 756 records; after duplicates deletion, 13 were considered eligible. The results reported that subjects with LBMD had kinematic alterations of the walk, alterations of posture, speed of walking and the strength generated in the gait. Patients with osteoporosis show a reduction of gait speed and trunk asymmetry; moreover, there is a a decrease in body rotation and lower hip and ankle moments in post-menopausal women.ConclusionsPatients with LBMD showed gait alterations that can higher the risk of falls. In this context, gait analysis can be useful in detecting variations in pattern, symmetry, gait speed and posture in elderly patients, that can represent an essential step for a personalized rehabilitation program.

Multiple lines of evidence suggest that multiple pathological conditions and diseases that account for the majority of human mortality are driven by the molecular aging process. At the cellular level, aging can largely be conceptualized to comprise the progressive accumulation of molecular damage, leading to resultant cellular dysfunction. As many diseases, e.g., cancer, coronary heart disease, Chronic obstructive pulmonary disease, Type II diabetes mellitus, or chronic kidney disease, potentially share a common molecular etiology, then the identification of such mechanisms may represent an ideal locus to develop targeted prophylactic agents that can mitigate this disease-driving mechanism. Here, using the input of artificial intelligence systems to generate unbiased disease and aging mechanism profiles, we have aimed to identify key signaling mechanisms that may represent new disease-preventing signaling pathways that are ideal for the creation of disease-preventing chemical interventions. Using a combinatorial informatics approach, we have identified a potential critical mechanism involving the recently identified kinase, Dual specificity tyrosine-phosphorylation-regulated kinase 3 (DYRK3) and the epidermal growth factor receptor (EGFR) that may function as a regulator of the pathological transition of health into disease via the control of cellular fate in response to stressful insults.

Background: Reduced bone mass and density, hallmark features of osteopenia and osteoporosis, significantly increase the risk of fractures, falls, and loss of mobility, especially in post-menopausal women and the elderly. Methods: This quantitative 7T MRI study examines the features of fibular bone thinning and bone mineral density loss (BMD) in 107 individuals (43F/64M) across various ages, body mass indices (BMIs), and ethnicities. Results: Women had significantly lower cross-sectional bone wall thickness (BT) and bone tissue area (BA), along with greater BMD loss compared to men in those over age 50 (n = 77), but not in the younger group (n = 30). The bone g-factor, defined as the ratio of inner-to-outer bone diameters, increased with bone thinning, bone marrow expansion (BME), and muscle fat infiltration (MFI) but was independent of subcutaneous fat thickness (SFT). Bone thinning and BMD loss both tend to increase with BME and MFI. Additionally, bone density decrease correlated with bone mass loss, with a stronger association observed with BT than BA. Conclusions: These findings offer insights into the effects of aging and sex on skeletomuscular health, with implications for strategies to mitigate bone loss in osteoporosis and osteosarcopenia.

We previously reported that PRDM16 mediated the improvement in body composition in testosterone (T)-treated hypogonadal men by shifting adipogenesis to myogenesis. Previous preclinical studies suggest that Prdm16 regulates Runx2, an important osteoblastic transcription factor, expression and activity. However, the changes in PRDM16, and other genes/proteins involved in osteoblastogenesis with T therapy in hypogonadal men are unexplored. We investigated the role of PRDM16 in RUNX2 activation by measuring changes in gene expression in peripheral blood monocytes (PBMCs) and proteins in the serum of hypogonadal men after T therapy for 6 months. Likewise, we evaluated changes in the WNT10b-β-CATENIN signaling pathway by gene expression and protein analyses. We found significant increases in PRDM16 and RUNX2 expression in PBMCs together with significant increases in serum proteins at 6 months when compared to baseline. There were also increases in gene and protein expressions of WNT10b, and β-CATENIN at 6 months. Furthermore, we found a significant positive correlation between % changes in PRDM16 and WNT10b. Our results suggest that T therapy activates PRDM16, leading to enhanced signaling in the canonical WNT10b-β-CATENIN-RUNX2 pathway, the pathway involved in osteoblastogenesis. The above findings may account for the improvement in bone density and quality in hypogonadal men treated with T.

As the global population ages, the incidence of age-related musculoskeletal diseases continues to increase, driven by numerous complex and poorly understood factors. WNT-1 inducible secreted protein 1 (WISP-1), a secreted matrix protein, plays a critical role in the growth and development of the musculoskeletal system, including chondrogenesis, osteogenesis, and myogenesis. Numerous in vivo and in vitro studies have demonstrated that WISP-1 is significantly upregulated in age-related musculoskeletal conditions, such as osteoarthritis, osteoporosis, and sarcopenia, suggesting its involvement in the pathogenesis of these diseases. Regulating WISP-1 expression holds promise as a therapeutic strategy for improving musculoskeletal function, potentially offering new avenues for treating age-related musculoskeletal diseases in clinical practice. This review highlights the signaling pathways associated with WISP-1, its physiological roles within the musculoskeletal system, and its therapeutic potential in treating age-related musculoskeletal disorders.

Computational analysis of the pubic symphyseal surface is widely used for accurate age estimation, offering quantitative precision through the detection of subtle morphological changes. However, these methods often lack insights into the underlying morphological changes across different age groups. To bridge this gap, the study utilizes statistical shape modeling (SSM), a versatile tool capable of describing diverse morphological variations within populations. This study aimed to elucidate the direction and extent of these morphological changes, identify the contributing factors, and pinpoint key variations crucial for distinguishing between age groups. Computed tomography (CT) scans of 252 subjects from the National Forensic Service of South Korea were employed, subjected to preprocessing and landmark-based alignment. Through this approach, the study visualized and validated significant age-related morphological changes and highlighted the shape variations essential for differentiating between consecutive age groups. This study holds significance in elucidating the intricate nature of age-related morphological changes in the pubic symphyseal surface. Thus, these findings can serve as valuable cornerstones for enhancing age-at-death estimation techniques in forensic anthropology.

Background: Age-related changes to the orbicularis oculi muscle include impaired eyelid function, such as lagophthalmos, alterations in tear film dynamics, and aesthetic changes like wrinkles, festoons, and the descent of soft tissue. To date, the structural and functional changes that would comprehensively increase our understanding of orbicularis aging have not been analyzed. This study aims to investigate functional outcomes using surface electromyography and correlate them with ultrastructural changes in orbicularis during aging. Methods: This study enrolled 26 patients aged 37 to 78 years with a clinical diagnosis of dermatochalasis. Patients were divided into two age groups (<60 years; ≥60 years). Ultrastructural and electromyographical examinations were performed, and the electromyographical signals were correlated with the ultrastructural damage in the orbicularis. Results: This study revealed significantly lower values of average voluntary contraction and RMS of the surface electromyography signals in the older age group compared to the younger age group (p = 0.029 and p = 0.045, respectively). There was no statistically significant association between age and muscle damage (χ2(2) = 2.86, p > 0.05). There was no correlation between average voluntary contraction and the degree of ultrastructural damage in both groups (Spearman's coefficient equaled 0.06923 and 0.64366, respectively). Conclusions: sEMG measurements are valuable for monitoring age-related functional changes in the orbicularis. Aging diminishes the functional capacity of the orbicularis, as evidenced by reduced contraction strength. This study, the first to compare ultrastructural and electromyographical changes in the orbicularis among dermatochalasis patients of different ages, finds that ultrastructural damage to muscle fibers is not directly responsible for the contraction strength decline.

Sarcopenia is a prevalent condition associated with aging. Inflammation and pyroptosis significantly contribute to sarcopenia.

Two sarcopenia-related datasets (GSE111016 and GSE167186) were obtained from the Gene Expression Omnibus (GEO), followed by batch effect removal post-merger. The "limma" R package was utilized to identify differentially expressed genes (DEGs). Subsequently, LASSO analysis was conducted on inflammation and pyroptosis-related genes (IPRGs), resulting in the identification of six hub IPRGs. A novel skeletal muscle aging model was developed and validated using an independent dataset. Additionally, Gene Ontology (GO) enrichment analysis was performed on DEGs, along with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and gene set enrichment analysis (GSEA). ssGSEA was employed to assess differences in immune cell proportions between healthy muscle groups in older versus younger adults. The expression levels of the six core IPRGs were quantified via qRT-PCR.

A total of 44 elderly samples and 68 young healthy samples were analyzed for DEGs. Compared to young healthy muscle tissue, T cell infiltration levels in aged muscle tissue were significantly reduced, while mast cell and monocyte infiltration levels were relatively elevated. A new diagnostic screening model for sarcopenia based on the six IPRGs demonstrated high predictive efficiency (AUC = 0.871). qRT-PCR results indicated that the expression trends of these six IPRGs aligned with those observed in the database.

Six biomarkers-BTG2, FOXO3, AQP9, GPC3, CYCS, and SCN1B-were identified alongside a diagnostic model that offers a novel approach for early diagnosis of sarcopenia.

PFAS may impair bone health, but effects of PFAS exposure assessed during pregnancy and the perimenopause-life stages marked by rapidly changing bone metabolism-on later life bone health are unknown.

We studied 531 women in the Boston-area Project Viva cohort. We used multivariable linear, generalized additive, and mixture models to examine associations of plasma PFAS concentrations during early pregnancy [median (IQR) maternal age 32.9 (6.2) years] and midlife [age 51.2 (6.3)] with lumbar spine, total hip, and femoral neck areal bone mineral density (aBMD) and bone turnover biomarkersassessed in midlife. We examined effect modification by diet and physical activity measured at the time of PFAS exposure assessment and by menopausal status in midlife.

Participants had higher PFAS concentrations during pregnancy [1999-2000; e.g., PFOA median (IQR) 5.4 (3.8) ng/mL] than in midlife [2017-2021; e.g.

1.5 (1.2) ng/mL]. Women with higher PFOA, PFOS and PFNA during pregnancy had higher midlife aBMD, especially of the spine [e.g., 0.28 (95% CI: 0.07, 0.48) higher spine aBMD T-score, per doubling of PFOA], with stronger associations observed among those with higher diet quality. In contrast, higher concentrations of all PFAS measured in midlife were associated with lower concurrent aBMD at all sites [e.g., -0.21 (-0.35, -0.07) lower spine aBMD T-score, per doubling of PFOA]; associations were stronger among those who were postmenopausal. The associations of several PFAS with bone resorption (loss) were also stronger among postmenopausal versus premenopausal women.

Plasma PFAS measured during pregnancy versus in midlife had different associations with midlife aBMD. We found an adverse association of PFAS measured in midlife with midlife aBMD, particularly among postmenopausal women. Future studies with longer follow-up are needed to elucidate the effect of PFAS on bone health during the peri- and postmenopausal years.

Low bone mineral density (LBMD) remains a global public health concern. To provide deeper insights, we retrieved and calibrated LBMD death and Disability-Adjusted Life Years (DALYs) data from the Global Burden of Disease 2021 (GBD 2021) database. We calculated the age-standardized rate (ASR) and estimated annual percentage change (EAPC) to delineate LBMD trends across sexes, age groups, Sociodemographic Index (SDI) regions, and countries. Spearman rank order correlation analysis was used to explore the relationship between SDI and ASR. Additionally, we constructed Bayesian age-period-cohort (BAPC) models to predict future trends in LBMD up to 2030, with the mean absolute percentage error (MAPE) used to evaluate prediction accuracy. Our analyses revealed that global deaths related to LBMD nearly doubled, from 250,930 in 1990 to 463,010 in 2021, and are projected to rise to 473,690 by 2030. However, the ASR exhibited an opposite trend, decreasing from 17.91 per 100,000 in 1990 to 15.77 per 100,000 in 2021, and is expected to further decline to 13.64 per 100,000 by 2030. The EAPC indicated descending trends in 1990-2021 and 2022-2030. Trends in LBMD varied across different subgroups by sex, age, and location. Males are projected to continue experiencing higher death numbers than females, though the gap is narrowing. The 90 to 94 age group consistently had the highest ASR from 1990 to 2030. Lower SDI remains a critical factor contributing to the higher burden of LBMD. Spearman rank order correlation analysis showed a negative correlation between SDI and ASR. We categorized 6 distinct trends in ASR across different countries, with most expected to experience a decline by 2030. The MAPE value (0.038 < 0.1) indicated that the BAPC model produced reliable predictions even under the COVID-19 pandemic.

Purpose: To investigate the effects of total knee arthroplasty (TKA) on muscle mass and bone density in end-stage knee osteoarthritis (OA). Methods: This prospective study was conducted on 111 patients with Kellgren-Lawrence grade 4 knee OA who underwent TKA after failing to respond to conservative treatment for more than 3 months at a single institution from June 2022 to May 2023. Appendicular lean mass index (ALMI) and bone mineral density (BMD) were measured using dual-energy X-ray absorptiometry before and every 6 months after surgery. The average follow-up period was 15.5 ± 2.31 months (range, 11.6-24 months). Results: During the follow-up period after TKA, the ALMI increased relatively continuously and consistently. The BMD of the L-spine and proximal femur did not change significantly until 12 months after TKA surgery but began to increase steeply after 12 months and slowed down after 18 months. The increase in muscle mass showed a significant positive correlation with the increase in BMD. Conclusions: Muscle mass gradually increased after TKA for end-stage knee OA, whereas bone density also increased but not until 12 months after surgery. The significant positive correlation between the increase in muscle mass and bone density suggests that the increase in muscle mass after TKA may be one of the causes of the increase in bone density.

The risk factors for contralateral hip refracture after primary hip fracture are not fully understood; therefore, this study compared the clinical characteristics of patients with first and second hip fractures and explored and analyzed the risk factors for contralateral refracture after hip fracture in elderly individuals to provide a reference for the clinical prevention of postoperative refracture of hip fracture in elderly individuals.

A retrospective study was conducted on 458 elderly patients with hip fractures who underwent surgical treatment and were discharged from our hospital from March 2016 to March 2019. The clinical data of the patients were analyzed retrospectively. Patients were divided into a case group (postoperative refracture) and a control group (no postoperative refracture) based on whether they experienced refracture within five years after surgery. The clinical data of the two groups were compared and analyzed via univariate and multivariate logistic regression analyses and receiver operating characteristic (ROC) regression analysis to identify the risk factors for refractures after hip fracture surgery in elderly patients.

Sixty-one patients experienced refracture, with an incidence rate of 13.3%. Age ≥ 80.5 years, female sex, poor knee joint function, FRAX score ≥ 15.5, anemia, visual impairment, osteoporosis, and Alzheimer's disease (AD) were identified as risk factors for refracture after hip fracture surgery in elderly individuals (P < 0.05).

Elderly patients with hip fractures are susceptible to refracture after surgery because of factors such as advanced age, female sex, high FRAX score, poor knee joint function, anemia, osteoporosis, visual impairment, and AD. Targeted interventions should be implemented based on the above risk factors.

Patients with osteoporosis (OP) are often associated with decreased hand grip strength and increased risk of falling. It remains unclear whether there is a genetic causal between hand grip strength and OP, falling risk.

The Mendelian randomization study was used to investigate the genetic causal effect of low hand grip strength on total body bone mineral density (BMD) at different ages, OP, and falling risk. Genes for low hand grip strength, total body BMD at different ages, OP, and falling risk were obtained from published genome-wide association studies. Inverse variance weighted, MR-Egger, and weighted median were applied to perform the MR analysis. The Cochran's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were used to detect the pleiotropy or heterogeneity.

The results showed strong evidence that low hand grip strength was positively associated with OP (OR: 1.006, 95% CI: 1.003-1.010; P= 0.0001) and falling risk (OR: 1.069, 95% CI: 1.013-1.129; P= 0.0160), and could not directly affect the different ages of total body BMD (P> 0.05). There was no heterogeneity or horizontal pleiotropy in the sensitivity analysis (all P> 0.05).

The study found a positive causal relationship between low hand grip strength and higher risk of OP and falling, which should be taken into account in the development of future prevention and screening strategies for OP and falling.

This study conducted transcriptome sequencing on the skeletal muscles of three different anatomical locations across various growth stages to investigate the impact of ages on crucial candidate genes and molecular mechanisms associated with muscle development in Kazakh horses. Sixteen Kazakh horses were selected, and they were divided into four age groups, each with four biological replicates. Tissue samples from the longest dorsal muscle, abdominal muscle, and diaphragm muscle were collected for analysis. The results revealed differential mRNA expression in the longest dorsal muscle between the eight-month group (Group O) and the 10-year group (Group F), with 434 up-regulated and 322 down-regulated genes. In the abdominal muscle, there were 125 up-regulated and 127 down-regulated genes, while in the diaphragm muscle, there were 73 up-regulated and 70 down-regulated genes. In this study, GO enrichment analysis focused on biological processes. KEGG pathway analysis highlighted the Oxidative Phosphorylation pathway for the longest dorsal muscle, annotating 37 differentially expressed genes (DEGs), including ATP5PF, NDUFB8, and ATP5MG, all of which were down-regulated. For the abdominal muscle, the ECM-receptor interaction pathway was enriched, annotating 7 DEGs such as COL4A2, COL4A1, and ITGA5. In the diaphragm muscle, the Hippo signaling pathway was enriched, annotating 6 DEGs, including SERPINE1, RASSF1, and FZD10. This study provides robust data support and a theoretical foundation for a comprehensive understanding of the influence of age on skeletal muscle development in horses.

Stress fracture is a concern among older adults, as age-related decrements in ankle neuromuscular function may impair their ability to attenuate tibial compressive forces experienced during daily locomotor tasks, such as stair descent. Yet, it is unknown if older adults exhibit greater tibial compression than their younger counterparts when descending stairs.

Do older adults exhibit differences in ankle biomechanics that alter their tibial compression during stair descent compared to young adults, and is there a relation between tibial compression and specific changes in ankle biomechanics?

Thirteen young (18-25 years) and 13 older (> 65 years) adults had ankle joint biomechanics and tibial compression quantified during a stair descent. Discrete ankle biomechanics (peak joint angle and moment, and joint stiffness) and tibial compression (maximum and impulse) measures were submitted to an independent t-test, while ankle joint angle and moment, and tibial compression waveforms were submitted to an independent statistical parametric mapping t-test to determine group differences. Pearson correlation coefficients (r) determined the relation between discrete ankle biomechanics and tibial compression measures for all participants, and each group.

Older adults exhibited smaller maximum tibial compression (p = 0.004) from decreases in peak ankle joint angle and moment between 17 % and 34 % (p = 0.035), and 20-31 % of stance (p < 0.001) than young adults. Ankle biomechanics exhibited a negligible to weak correlation with tibial compression for all participants, with peak ankle joint moment and maximum tibial compression (r = -0.48 ± 0.32) relation the strongest. Older adults typically exhibited a stronger relation between ankle biomechanics and tibial compression (e.g., r = -0.48 ± 0.47 vs r = -0.27 ± 0.52 between peak ankle joint moment and maximum tibial compression).

Older adults altered ankle biomechanics and decreased maximum tibial compression to safely execute the stair descent. Yet, specific alterations in ankle biomechanics could not be identified as a predictor of changes in tibial compression.

Dietary supplement use is common among US adults. We aimed to investigate the quantity, duration, adherence, and reasons for supplement use in individuals who take supplements. Data from 2011 to 2018 from the National Health and Nutrition Examination Survey (NHANES) dataset were analyzed. Four cycles of data were combined to estimate these outcomes. Results are presented as overall group and by subgroups. All analyses were weighted to be nationally representative. The Taylor Series Linearization approach was used to generate variance estimates. A total of 12,529 participants were included. Over 70% of these individuals reported taking more than one unit of dietary supplements daily. Notably, approximately 40% had been taking supplements for more than five years and about 67% were highly adherent to at least one supplement. However, only 26.9% of these supplements were taken following a doctor's recommendation. The primary reasons for dietary supplements intake included improving overall health (37.2%), maintaining health (34.7%), bone health (21.4%), and diet supplementation (20.3%). Our findings indicate that most participants proactively used multiple dietary supplements focused on self-managed health and prevention, with substantial dedication to long-term use and high adherence. Healthcare professionals should play a more active role in guiding such behaviors to optimize the health outcomes of dietary supplement users across the United States.

Low grip strength and gait speed are associated with mortality. However, investigation of the additional mortality risk explained by these measures, over and above other factors, is limited.

We examined whether grip strength and gait speed improve discriminative capacity for mortality over and above more readily obtainable clinical risk factors.

Participants from the Health, Aging and Body Composition Study, Osteoporotic Fractures in Men Study, and the Hertfordshire Cohort Study were analysed. Appendicular lean mass (ALM) was ascertained using DXA; muscle strength by grip dynamometry; and usual gait speed over 2.4-6 m. Verified deaths were recorded. Associations between sarcopenia components and mortality were examined using Cox regression with cohort as a random effect; discriminative capacity was assessed using Harrell's Concordance Index (C-index).

Mean (SD) age of participants (n = 8362) was 73.8(5.1) years; 5231(62.6%) died during a median follow-up time of 13.3 years. Grip strength (hazard ratio (95% CI) per SD decrease: 1.14 (1.10,1.19)) and gait speed (1.21 (1.17,1.26)), but not ALM index (1.01 (0.95,1.06)), were associated with mortality in mutually-adjusted models after accounting for age, sex, BMI, smoking status, alcohol consumption, physical activity, ethnicity, education, history of fractures and falls, femoral neck bone mineral density (BMD), self-rated health, cognitive function and number of comorbidities. However, a model containing only age and sex as exposures gave a C-index (95% CI) of 0.65(0.64,0.66), which only increased to 0.67(0.67,0.68) after inclusion of grip strength and gait speed.

Grip strength and gait speed may generate only modest adjunctive risk information for mortality compared with other more readily obtainable risk factors.

Ipsilateral femoral neck fractures can be seen alongside femoral shaft fractures in high-velocity trauma patients. These neck fractures are often occult on radiographs and CT, and can have a significant impact on patient outcomes if not treated promptly. Limited protocol pelvic MRI has been used to increase sensitivity for these occult fractures. Detailed characterization of these fractures on MRI is lacking.

427 consecutive trauma patients presenting to our emergency department who had known femoral diaphyseal fractures but no ipsilateral femoral neck fracture on radiographs or CT were included in this study. These patients were scanned using a limited protocol MRI with coronal T1 and coronal STIR sequences. Presence of an ipsilateral femoral neck fracture and imaging characteristics of the fracture were obtained.

31 radiographically occult ipsilateral femoral neck fractures were found, representing 7% of all cases. All neck fractures were incomplete. All fractures originated along the lateral cortex of the femoral neck and extended medially towards the junction of the medial femoral neck and the lesser trochanter. 58% (18/31) were vertical in orientation. 61% (19/31) did not demonstrate any appreciate edema on STIR images.

Implementation of limited protocol MRI protocol increases sensitivity for detection of femoral neck fractures in the setting of ipsilateral femoral shaft fractures not seen on radiograph or CT imaging. We describe the characteristic MR imaging features of these fractures.

Muscle and bone tissue are interrelated throughout their developmental processes via paracrine and endocrine pathways. Osteosarcopenia has emerged with the growing data proving the high rate of simultaneous occurrence of sarcopenia and osteoporosis. We aimed to evaluate the relationship between osteoporosis, and muscle quality by grading the fatty infiltration in paraspinal muscles according to the Goutallier classification in magnetic resonance imaging (MRI).

Data of postmenopausal patients who underwent MRI for low back pain were analyzed retrospectively. Lumbar spine and femoral neck bone mineral density (BMD) were measured by using dual energy X-ray absorptiometry (DXA). Grade of paraspinal muscle fatty infiltration for each level of lumbar vertebrae including L1-L2, L2-L3, L3-L4, was evaluated separately according to Goutallier classification system.

A total of 91 postmenopausal women were included in the study. The mean age of the study population was 60.5 ± 11. Lumbar vertebrae L1-L4 total T-scores and BMD g/cm2 were lower in patients with higher grades of Goutallier classification (P = 0.031 and P = 0.023, respectively). The distribution of the severity of fatty degeneration was significantly higher in the osteoporosis/osteopenia group at all 3 disc levels. No significant correlation was observed between femoral neck BMD and paraspinal muscle fat infiltration.

There is a strong relationship between osteoporosis of the lumbar spine and paraspinal muscle quality, which can be considered as a reflection of osteosarcopenia. The Goutailler classification can be an effective and easy method in the evaluation of muscle quality with MRI.

To determine whether body composition derived from medical imaging may be useful for assessing biologic age at the tissue level because people of the same chronologic age may vary with respect to their biologic age.

We identified an age- and sex-stratified cohort of 4900 persons with an abdominal computed tomography scan from January 1, 2010, to December 31, 2020, who were 20 to 89 years old and representative of the general population in Southeast Minnesota and West Central Wisconsin. We constructed a model for estimating tissue age that included 6 body composition biomarkers calculated from abdominal computed tomography using a previously validated deep learning model.

Older tissue age associated with intermediate subcutaneous fat area, higher visceral fat area, lower muscle area, lower muscle density, higher bone area, and lower bone density. A tissue age older than chronologic age was associated with chronic conditions that result in reduced physical fitness (including chronic obstructive pulmonary disease, arthritis, cardiovascular disease, and behavioral disorders). Furthermore, a tissue age older than chronologic age was associated with an increased risk of death (hazard ratio, 1.56; 95% CI, 1.33 to 1.84) that was independent of demographic characteristics, county of residency, education, body mass index, and baseline chronic conditions.

Imaging-based body composition measures may be useful in understanding the biologic processes underlying accelerated aging.

(1) Background: With the aging population, effective interventions are needed to enhance the health of older adults. This study investigated the combined effects of yoga and the Mediterranean diet on various health outcomes in community-dwelling older adults; (2) Methods: The study employed a randomized controlled trial design with a total of 116 older adults randomized to an experimental group (n = 57) that underwent a combined yoga and Mediterranean diet program and a control group (n = 59) that did not receive any intervention. Nutritional status was assessed using the Mini Nutritional Assessment, flexibility with the Back Scratch Test and the Chair Sit-and-Reach Test, balance, gait, and fall risk with the Tinetti Scale, and muscle strength with a dynamometer and the 30 s Chair Stand Test; (3) Results: Regarding nutritional status, there were significant differences between the experimental group and the control group (Cohen's d = 0.02). The participants in the experimental group showed greater balance (11.12 ± 3.01 vs. 10.03 ± 2.35, Cohen's d = 0.41 and gait (7.63 ± 1.96 vs. 6.69 ± 2.50, Cohen's d = 0.44) with respect to the control group. In terms of flexibility, the experimental group showed statistically significant improvements in the right arm (Cohen's d = 0.43), left arm (Cohen's d = 0.64), right perineum (Cohen's d = 0.42), and left leg (Cohen's d = 0.37) Finally, in terms of strength, participants in the experimental group experienced statistically significant improvements in grip strength and lower body strength (Cohen's d = 0.39 and 0.81, respectively); (4) Conclusions: The study highlights the potential benefits of a 12-week intervention combining yoga with a Mediterranean diet to improve the health and functional capacities of community-dwelling older adults.

Muscle and bone tissues are interconnected, and both rely on an adequate protein intake. Recommendations for protein intake for older adults specifically vary across countries. The purpose of this narrative review is to discuss the existing evidence for protein recommendations for supporting muscle and bone health in older adults and to evaluate if a protein intake above the current population reference intake (PRI) for older adults would be scientifically justified. First, this review summarizes the protein recommendations from bodies setting dietary reference values, expert groups, and national health organizations. Next, relevant studies investigating the impact of protein on muscle and bone health in older adults are discussed. In addition, the importance of protein quality for muscle and bone health is addressed. Lastly, a number of research gaps are identified to further explore the added value of a protein intake above the PRI for older adults.

Cardiopulmonary resuscitation (CPR) is a life-saving technique used in emergencies when the heart stops beating, typically involving chest compressions and ventilation. Current adult CPR guidelines do not differentiate based on age beyond infancy and childhood. This oversight increases the risk of fatigue fractures in the elderly due to decreased bone density and changes in thoracic structure. Therefore, this study aimed to investigate the correlation and impact of factors influencing rib fatigue fractures for safer out-of-hospital manual cardiopulmonary resuscitation (OHMCPR) application. Using the finite element analysis (FEA) method, we performed fatigue analysis on rib cage models incorporating chest compression conditions and age-specific trabecular bone properties. Fatigue life analyses were conducted on three age-specific rib cage models, each differentiated by trabecular bone properties, to determine the influence of four explanatory variables (the properties of the trabecular bone (a surrogate for the age of the subject), the site of application of the compression force on the breastbone, the magnitude of applied compression force, and the rate of application of the compression force) on the fatigue life of the model. Additionally, considering the complex interaction of chest compression conditions during actual CPR, we aimed to predict rib fatigue fractures under conditions simulating real-life scenarios by analyzing the sensitivity and interrelation of chest compression conditions on the model's fatigue life. Time constraints led to the selection of optimal analysis conditions through the use of design of experiments (DOE), specifically orthogonal array testing, followed by the construction of a deep learning-based metamodel. The predicted fatigue life values of the rib cage model, obtained from the metamodel, showed the influence of the four explanatory variables on fatigue life. These results may be used to devise safer CPR guidelines, particularly for the elderly at a high risk of acute cardiac arrest, safeguarding against potential complications like fatigue fractures.

Eggs offer a range of essential nutrients that could support skeletal health as individuals age. Maintaining bone density is crucial for reducing the risk of fractures and improving overall mobility and quality of life in later years. Understanding the potential benefits of habitual egg consumption on bone mass density among older people is essential, given that the natural decline in bone mass density occurs with age. This area of research has not garnered sufficient attention basically because of the mixed reactions and conflicting reports about the safety of egg consumption especially among the older adults. This scoping review aims to systematically examine the existing literature to map the evidence regarding the association between habitual egg consumption and bone mass density in older adults' individuals. The scoping review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines to ensure methodological rigor and transparency. Five electronic databases were searched for published pieces of literature. While high egg intake has been linked to increased mortality and dyslipidemia, eggs contain compounds like Ovo transferrin and carotenoids that may benefit bone health. As aging increases vulnerability to bone fragility and fractures, it's crucial to provide comprehensive dietary recommendations. The complex relationship between egg consumption, cholesterol, and health highlights the need for nuanced assessment. Overall, eggs present a potentially valuable dietary component for promoting bone health in aging populations. Limited research on the link between egg consumption and bone mass density in older adults highlights the need for further investigation. Concerns about cholesterol have overshadowed potential benefits. Given aging populations and bone health challenges, exploring eggs' role in preventing falls and fractures is essential for a proactive approach to older adults' well-being.

Hip fractures are prevalent among older people, often leading to reduced mobility, muscle loss, and bone density decline. Malnutrition exacerbates the prognosis post surgery. This study aimed to evaluate the impact of a 12-week regimen of a high-calorie, high-protein oral supplement with β-hydroxy-β-methylbutyrate (HC-HP-HMB-ONS) on nutritional status, daily activities, and compliance in malnourished or at-risk older patients with hip fractures receiving standard care.

A total of 270 subjects ≥75 years of age, residing at home or in nursing homes, malnourished or at risk of malnutrition, and post hip fracture surgery, received HC-HP-HMB-ONS for 12 weeks. Various scales and questionnaires assessed outcomes.

During the 12 weeks of follow-up, 82.8% consumed ≥75% of HC-HP-HMB-ONS. By week 12, 62.4% gained or maintained weight (+0.3 kg), 29.2% achieved normal nutritional status (mean MNA score +2.8), and 46.8% improved nutritional status. Biochemical parameters improved significantly. Subjects reported good tolerability (mean score 8.5/10), with 87.1% of healthcare providers concurring.

The administration of HC-HP-HMB-ONS markedly enhanced nutritional status and biochemical parameters in older hip-fracture patients, with high compliance and tolerability. Both patients and healthcare professionals expressed satisfaction with HC-HP-HMB-ONS.

Shoulder pain and disabilities are prevalent issues among the elderly population, with rotator cuff tear (RCT) being one of the leading causes. Although surgical treatment has shown some success, high postoperative retear rates remain a great challenge, particularly in elderly patients. Aging-related degeneration of muscle, tendon, tendon-to-bone enthesis, and bone plays a critical role in the development and prognosis of RCT. Studies have demonstrated that aging worsens muscle atrophy and fatty infiltration, alters tendon structure and biomechanical properties, exacerbates enthesis degeneration, and reduces bone density. Although recent researches have contributed to understanding the pathophysiological mechanisms of aging-related RCT, a comprehensive systematic review of this topic is still lacking. Therefore, this article aims to present a review of the pathophysiological changes and their clinical significance, as well as the molecular mechanisms underlying aging-related RCT, with the goal of shedding light on new therapeutic approaches to reduce the occurrence of aging-related RCT and improve postoperative prognosis in elderly patients.

Therapeutic advances in the management of osteoporosis and sarcopenia have occurred at different rates over the last 2 decades. Here we examine associations between grip strength and BMD with subsequent all-cause and cause-specific mortality in a UK community-dwelling cohort.

Data from 495 men and 414 women from the Hertfordshire Cohort Study were analysed. Grip strength was assessed by grip dynamometry, femoral neck BMD was ascertained using DXA and deaths were recorded from baseline (1998-2004) until 31 December 2018. Grip strength and BMD in relation to mortality outcomes (all-cause, cardiovascular-related, cancer-related and mortality due to other causes) were examined using Cox regression with adjustment for age and sex.

The mean baseline age of participants was 64.3 years (s.d. 2.5) and 65.9 years (s.d. 2.6) in men and women, respectively. Lower grip strength was associated with increased risk of all-cause mortality [hazard ratio (HR) 1.30 (95% CI 1.06, 1.58), P = 0.010] and cardiovascular-related mortality [HR 1.75 (95% CI 1.20, 2.55), P = 0.004]. In contrast, BMD was not associated with any of the mortality outcomes (P > 0.1 for all associations).

We report strong relationships between grip strength and mortality compared with BMD. We hypothesize that this may reflect better recognition and treatment of low BMD in this cohort.

Skeletal muscles are important for body movement, postural maintenance, and energy metabolism. Muscle atrophy is caused by various factors, including lack of exercise, age, genetics, and malnutrition, leading to the loss of muscle mass. The Akt/FoxO signaling pathway plays a key role in the regulation of muscle protein synthesis and degradation. Whole wheat contains functional ingredients that may indirectly contribute to muscle health and function and can help prevent or slow the progression of muscle atrophy. In this study, the protective effects of three wheat cultivars (Seodun, Ol, and Shinmichal 1) against hydrogen peroxide-induced muscle atrophy in C2C12 cells were investigated. We found that whole-wheat treatment reduced reactive oxygen species production, prevented glutathione depletion, and increased myotube diameter, thereby reducing muscle atrophy by activating myoblast differentiation. Generally, "Shinmichal 1" exhibited the highest activation of the Akt/FoxO signaling pathway. In contrast, "Seodun" showed similar or slightly higher activities than those of the H2O2-treated only group. In conclusion, whole wheat exerts a protective effect against muscle atrophy by activating the Akt/FoxO signaling pathway. This study indicates that whole wheat may help prevent muscle atrophy.

Fibroblast growth factor 21 (FGF21) has been developed as a potential therapeutic agent for metabolic syndromes. Moreover, FGF21 is considered a pro-longevity hormone because transgenic mice overexpressing FGF21 display extended lifespan, raising the possibility of using FGF21 to promote healthy aging. We recently showed that visceral fat directed FGF21 gene therapy improves metabolic and immune health in insulin resistant BTBR mice. Here, we used a fat directed rAAV-FGF21 vector in 17-month-old female mice to investigate whether long-term FGF21 gene transfer could mitigate aging-related functional decline. Animals with FGF21 treatment displayed a steady, significant lower body weight over 7-month of the study compared to age-matched control mice. FGF21 treatment reduced adiposity and increased relative lean mass and energy expenditure associated with almost 100 folds higher serum level of FGF21. However, those changes were not translated into benefits on muscle function and did not affect metabolic function of liver. Overall, we have demonstrated that a single dose of fat-directed AAV-FGF21 treatment can provide a sustainable, high serum level of FGF21 over long period of time, and mostly influences adipose tissue homeostasis and energy expenditure. High levels of FGF21 alone in aged mice is not sufficient to improve liver or muscle functions.