With global population aging, age-related diseases, especially sarcopenia, have attracted much attention in recent years. Characterized by low muscle strength, low muscle quantity or quality and low physical performance, sarcopenia is one of the major factors associated with an increased risk of falls and disability. Much effort has been made to understand the cellular biological and physiological mechanisms underlying sarcopenia. Autophagy is an important cellular self-protection mechanism that relies on lysosomes to degrade misfolded proteins and damaged organelles. Research designed to obtain new insight into human diseases from the autophagic aspect has been carried out and has made new progress, which encourages relevant studies on the relationship between autophagy and sarcopenia. Autophagy plays a protective role in sarcopenia by modulating the regenerative capability of satellite cells, relieving oxidative stress and suppressing the inflammatory response. This review aims to reveal the specific interaction between sarcopenia and autophagy and explore possible therapies in hopes of encouraging more specific research in need and unlocking novel promising therapies to ameliorate sarcopenia.

Proteoglycan 4 (PRG4), also known as lubricin, plays a critical role in maintaining joint homeostasis by reducing friction between articular cartilage surfaces and preventing cartilage degradation. Its deficiency leads to early-onset osteoarthritis (OA), while overexpression can protect against cartilage degeneration. Beyond its lubricating properties, PRG4 exerts anti-inflammatory effects by interacting with Toll-like receptors, modulating inflammatory responses within the joint. The expression of Prg4 is regulated by various factors, including mechanical stimuli, inflammatory cytokines, transcription factors such as Creb5 and FoxO, and signaling pathways like TGF-β, EGFR, and Wnt/β-catenin. Therapeutic strategies targeting PRG4 in OA have shown promising results, including recombinant PRG4 protein injections, gene therapies, and small molecules that enhance endogenous Prg4 expression or mimic its function. Further research into the molecular mechanisms regulating Prg4 expression will be essential in developing more effective OA treatments. Understanding the interplay between Prg4 and other signaling pathways could reveal novel therapeutic targets. Additionally, advancements in gene therapy and biomaterials designed to deliver PRG4 in a controlled manner may hold potential for the long-term management of OA, improving patient outcomes and delaying disease progression.

HYBID is a new hyaluronan-degrading enzyme and exists in various cells of the human body. Recently, HYBID was found to over-express in the osteoarthritic chondrocytes and fibroblast-like synoviocytes. According to these researches, high level of HYBID is significantly correlated with cartilage degeneration in joints and hyaluronic acid degradation in synovial fluid. In addition, HYBID can affect inflammatory cytokine secretion, cartilage and synovium fibrosis, synovial hyperplasia via multiple signaling pathways, thereby exacerbating osteoarthritis. Based on the existing research of HYBID in osteoarthritis, HYBID can break the metabolic balance of HA in joints through the degradation ability independent of HYALs/CD44 system and furthermore affect cartilage structure and mechanotransduction of chondrocytes. In particular, in addition to HYBID itself being able to trigger some signaling pathways, we believe that low-molecular-weight hyaluronan produced by excess degradation can also stimulate some disease-promoting signaling pathways by replacing high-molecular-weight hyaluronan in joints. The specific role of HYBID in osteoarthritis is gradually revealed, and the discovery of HYBID raises the new way to treat osteoarthritis. In this review, the expression and basic functions of HYBID in joints were summarized, and reveal potential role of HYBID as a key target in treatment for osteoarthritis.

The “weekend warrior” (WW) physical activity pattern—characterized by low-frequency, high-intensity exercise concentrated in 1–2 sessions per week—has gained popularity, yet its health implications remain controversial. This systematic review and meta-analysis aim to evaluate the benefits and risks of the WW pattern compared to regular or inactive PA regimens, focusing on mortality, cardiometabolic and neurological outcomes. Two independent investigators searched PubMed, Embase, Cochrane Library, and Web of Science for studies published from 01/01/1975 to 01/22/2025. Eligible studies compared health outcomes among WW, regularly active (RA), and inactive populations were included. Outcomes included all-cause/cause-specific mortality, cardiovascular disease (CVD), metabolic disorders, and neurological conditions. Pooled hazard ratios (HR) and odds ratios (OR) were calculated by either random-effects model or fixed-effects model, depending on heterogeneity. Among the 21 included studies (14 cohort, 7 cross-sectional), WW was associated with reduced all-cause mortality risk versus inactive population (HR = 0.77; 95% CI: 0.68–0.87, P < 0.0001), comparable to the benefit observed with RA (HR = 0.70; 95% CI: 0.63–0.78, P < 0.00001). WW was also linked to reduced risks of CVD mortality (HR = 0.80; 95% CI: 0.66–0.97), cancer mortality (HR = 0.85; 95% CI: 0.77–0.95), and incident CVD (HR = 0.73; 95% CI: 0.64–0.82) when compared with inactivity. Notably, WW conferred greater neuroprotective effects than RA (HR = 0.71 vs. 0.76; P < 0.00001), with a substantial risk reduction compared with inactivity (HR = 0.71; 95% CI: 0.65–0.77). Risk of metabolic disease in WW showed a modest decrease (OR = 0.75; 95% CI: 0.65–0.88, P = 0.0004), although no significant improvements were observed in individual metabolic indices. Compared with inactivity, the WW pattern offers mortality and cardiometabolic benefits comparable to regular activity, along with uniquely enhanced neuroprotective effects, supporting its viability for time-constrained individuals. PROSPERO: CRD42024583406.

Background: Osteoporosis (OP) is a systemic bone disease often undiagnosed until fractures occur. Metabolites may influence OP, offering potential biomarkers or therapeutic targets. This study investigates the causal relationship between circulating metabolites and OP-related phenotypes using Mendelian Randomization (MR). Methods: GWAS data on 233 metabolic traits from 136,016 participants were analyzed through two-sample MR. Linkage disequilibrium score regression (LDCS) was used to estimate genetic correlations between metabolic traits and OP-related phenotypes, leveraging European ancestry linkage disequilibrium scores to account for polygenicity and stratification. MR employed the inverse-variance weighted (IVW) method, with sensitivity analyses via MR-Egger, MR-PRESSO, and weighted median methods to address pleiotropy and confounders. Results: LDCS identified significant genetic correlations between metabolites and bone mineral density (BMD) phenotypes, with total body BMD (toBMD) showing the strongest associations. Thirty-five metabolite traits, including apolipoprotein A-I, exhibited significant linkages. Among 79 metabolites influencing BMD, serum acetate levels were significantly associated with femoral neck BMD (OR: 1.28, 95% CI: 1.02–1.62), lumbar spine BMD (OR: 1.73, 95% CI: 1.32–2.27), and total body BMD (OR: 1.21, 95% CI: 1.04–1.42). Creatinine levels were consistently linked to reduced BMD, including lumbar spine BMD (OR: 0.88, 95% CI: 0.79–0.99). Triglycerides in IDL and VLDL particles also contributed to BMD variation. Conclusions: Significant genetic correlations and causal relationships were observed between specific metabolites and OP, highlighting key traits as potential biomarkers of bone health. These findings enhance the understanding of OP pathogenesis and suggest future preventive strategies.

Recent reports suggest that the COVID-19 pandemic and associated lockdowns may have influenced the epidemiology of osteoporotic fractures, but results vary across regions and fracture types. The aim of this study was to provide evidence-based insights into the impact of the pandemic on osteoporotic fracture incidence. We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) up to August 2025 for observational or retrospective studies comparing osteoporotic fracture incidence during the COVID-19 pandemic (2020) with the pre-pandemic period (2019). The primary outcome of interest was the change in fracture incidence, analysed using risk ratios (RR) with 95% confidence intervals (CI) in Review Manager 5.4. Subgroup analyses were performed by sex, geographic region, and fracture type. Nine studies meeting the inclusion criteria were analysed. Overall, "all types" of osteoporotic fractures showed a significant decrease during the pandemic (RR = 0.85, 95% CI 0.80-0.91, p < 0.0001). Specifically, forearm fractures decreased significantly (RR = 0.87, 95% CI 0.79-0.96, p = 0.002). However, for the most clinically significant fractures, no statistically significant global change was found for hip fractures (RR = 0.93, 95% CI 0.76-1.15, p = 0.14) or vertebral fractures (RR = 1.35, 95% CI 0.85-2.15, p = 0.20). In regional subgroup analysis, hip fracture incidence decreased significantly in South America (RR = 0.79, p = 0.0004) and in both males and females, but no significant change was observed in Europe (RR = 0.92, 95% CI 0.81-1.04, p = 0.17). During the COVID-19 pandemic, there was a decrease in the incidence of minor fractures, such as those of the forearm, likely due to reduced outdoor activity. However, the incidence of major osteoporotic fractures (hip and vertebral) remained stable globally, with significant reductions observed only in specific regions like South America.