2026-03-30
Konstantin Warneke, Andreas Stotz, Andreas Konrad, Astrid Zech
PurposeFalls cause serious injuries with partially long immobilization time and decreased quality of life in older adults. The risk factors comprise instability in gait and balance, which were moderately correlated with the strength capacity. While the literature focused on upper-limb strength, in this work, we sought to evaluate the relationship between maximal plantar flexion and dorsiflexion strength and walking and balance parameters in older adults.MethodsA total of 51 healthy and active participants (age: 78.5 ± 5.8 years) participated in the study. Lower-leg maximal strength was determined isometrically. Selected gait parameters (normal and maximal walking velocity), static balance [center of pressure (CoP) sway in different standing conditions], and the timed up and go (TUG) and sit-to-stand (STS) were determined. Correlations [Pearson (rp)/Spearman (rs)] were calculated in general and stratified by sex.ResultsWalking velocity, STS, and TUG were significantly influenced by lower-leg strength (rs up to 0.79 in males). Static balance showed no meaningful relationships. In general, fewer correlations in female participants reached the level of significance and showed smaller effect sizes.DiscussionAlthough smaller sex-subgroup sample sizes might limit confidence in the results, male participants showed higher correlations between strength and walking velocity (up to rs = 0.79) and individual balance parameters (rs = 0.77) than female participants (rs = 0.56 for gait, rs = 0.72 for TUG). The results align with previous studies showing a potential influence of strength on gait parameters; however, a causal relationship must be confirmed by longitudinal study designs. Nevertheless, based on the results, there is a need for future sex-specific studies on the necessity of sex-specific balance and fall-prevention routines.
DOI: 10.3389/fragi.2026.17365172026-03-27
Liliana Andrea López Moreno, Carlos Moreno Pascual, María Consuelo Sancho Sánchez, Alejandro Moreno-Mateos
IntroductionExercise programs implemented among older adults have been extensively demonstrated to yield significant benefits; however, there is a limited body of research addressing the application of such interventions in older adults with severe or profound intellectual disabilities. This study aims to explore the effects of a structured physical exercise program on fall-risk indicators and balance-related outcomes in institutionalized older adults, both with and without intellectual disabilities.MethodsThis pre–post quasi-experimental study included 56 institutionalized older adults, of whom 32 had an intellectual disability. Participants completed a 12-week structured physical exercise program targeting balance, lower-limb strength, gait pattern, and coordination. The primary hypothesis was that the program would be associated with improvements in validated fall-risk indicators within both groups.ResultsAmong participants with intellectual disabilities, significant improvements were observed in lower-limb strength (p < 0.001) and aerobic capacity, with a 12% increase in performance on the 6-Minute Walk Test (p < 0.001). In participants without intellectual disabilities, significant improvements were observed in balance and handgrip strength. Between-group differences were limited after adjustment for baseline values and age.ConclusionThe intervention was associated with improvements in validated fall-risk functional indicators in institutionalized older adults with and without intellectual disabilities. However, due to baseline heterogeneity and the quasi-experimental design, the findings should be interpreted as preliminary and hypothesis-generating rather than confirmatory of equivalent effectiveness.
DOI: 10.3389/fragi.2026.17719082026-03-18
Robin Mathieu, Florian Chambellant, Denis Barbusse, Elizabeth Thomas, Charalambos Papaxanthis, Pauline M. Hilt, Patrick Manckoundia, France Mourey, Jeremie Gaveau
BackgroundAs the global population ages, it is crucial to understand sensorimotor compensation mechanisms. These mechanisms are thought to enable older adults to remain in good physical health, but despite important research efforts, their precise nature remains elusive and has not been definitively demonstrated. A major problem with their identification is the ambiguous interpretation of age-related alterations. Whether a change reflects deterioration or compensation is difficult to determine.MethodsTo address this challenge, we examined movement efficiency in younger and older adults using two complementary approaches. In Experiment 1 (Younger, n = 20; mean age = 23.6 years, and older adults, n = 24; mean age = 72 years), we quantified energetic efficiency through the negativity of phasic EMG activity—an established marker of how the nervous system exploits gravity to minimize muscular effort—during both single-joint arm movements and whole-body actions (sit-to-stand/back-to-sit and whole-body reaching). In Experiment 2 (younger adults, n = 20; mean age = 22.9 years; older adults, n = 20; mean age = 70.6 years), we directly measured energetic cost using exhaled-gas analysis during treadmill walking under varying balance constraints.ResultsIn Experiment 1, older adults preserved efficient planning during arm movements, but they showed reduced gravity-related efficiency during whole-body tasks. Complementary center-of-mass analyses and optimal control simulations indicated that this reduced efficiency aligned with movement strategies favoring stability over energy minimization. In Experiment 2, older adults exhibited a disproportionately larger increase in metabolic cost and perceived effort when equilibrium demands were elevated, despite performing the same tasks as younger adults.DiscussionThis supports a causal role of equilibrium constraints in decreasing walking efficiency in older adults. Overall, these results suggest that reduced movement efficiency in healthy older adults does not reflect a deterioration but rather a compensation process that adapts movement strategy to the task specificities. When balance is at stake, healthy older adults prefer stability to energy efficiency.
DOI: 10.3389/fragi.2026.17157232026-03-17
Mi Chen, Hongxiang Zheng, Rui Bai, Yingjie Huang, Guoyu Pang, Haixia Zhu, Zhuoxin Yi, Wenhui Chen
BackgroundEndothelial dysfunction under high-glucose conditions is a key pathological process contributing to the development and progression of diabetic osteoporosis (DOP). High glucose-induced damage to H-type vascular endothelial cells (H-type ECs), including mitochondrial dysfunction, increased lipid peroxidation, and activation of ferroptosis, is considered a potential mechanism underlying bone loss and dysregulated bone metabolism in DOP. Diabetic osteoporosis is a common and severe complication in patients with diabetes, and current clinical treatment options remain limited. Ginsenoside Rg1 (Rg1), one of the main active components of ginseng, has been shown to possess antioxidant and anti-osteoporotic effects, but its underlying mechanisms in DOP remain unclear.MethodsIn this study, spontaneously diabetic GK rats and high-glucose-treated H-type ECs were used to establish in vivo diabetic osteoporosis models and in vitro cell models, respectively. The effects of Rg1 on bone loss in GK rats as well as on mitochondrial function and lipid peroxidation in H-type ECs were evaluated. In vivo and in vitro experiments were conducted to investigate the potential mechanisms of Rg1 in regulating mitochondrial function and the SLC3A2/SLC7A11-GPX4 signaling pathway.ResultsOur results showed that, compared with the model group, Rg1 at different doses effectively reduced systemic bone loss, with no significant difference between medium and high doses. Compared with the ferroptosis activator and inhibitor groups, Rg1 inhibited ferroptosis and promoted H-type vessel formation. Furthermore, in vitro experiments confirmed these findings and demonstrated that Rg1 activated the SLC3A2/SLC7A11-GPX4 signaling pathway, while modulating H-type ECs mitochondrial membrane potential, decreasing mitochondrial reactive oxygen species (mtROS), and increasing lipid peroxidation.ConclusionOur study demonstrated that Rg1 promotes vessel–osteoblast coupling and regulates bone metabolism, thereby delaying the progression of diabetic osteoporosis (DOP). The underlying mechanism may involve activation of GPX4 expression in coordination with the regulation of H-type ECs mitochondrial membrane potential, leading to decreased mtROS levels and increased lipid peroxidation, ultimately intervening in ferroptosis. These findings highlight the GPX4–mitochondria cooperative regulation of H-type ECs ferroptosis by Rg1 and provide a new potential avenue for DOP therapy.
DOI: 10.3389/fragi.2026.17362632026-03-09
Chen Tianpeng, Xia Qishui, Yang Fo, Wu Mingjun, Hu Haibo, Jin Jiuchu, Shi Xiaolin, Jiang Gongtao
Osteoporotic non-vertebral fractures are a major clinical burden, with cortical bone impairment being a key pathogenic factor often overlooked in traditional treatments. This review aims to synthesize current evidence on the role of Wnt16 (a non-canonical Wnt ligand) in regulating cortical bone and its potential as a therapeutic target for osteoporotic non-vertebral fractures. We systematically review literature on Wnt16 in senile, postmenopausal, and glucocorticoid-induced osteoporosis, focusing on its mechanisms of action: (1) regulating bone mineral density via genetic associations with GWAS-identified loci; (2) reducing cortical bone porosity and increasing thickness; (3) dual regulation of osteoblasts (via JNK/β-catenin pathways) and osteoclasts (via OPG-dependent/independent NF-κB pathways). Wnt16 has been shown to improve bone density and reduce non-vertebral fracture risk in preclinical models, though conflicting findings exist regarding its full compensation for glucocorticoid-induced bone loss. We conclude that Wnt16 is a promising target for non-vertebral fracture prevention, with Notum inhibitors emerging as potential therapeutic agents. This review provides a comprehensive framework for future clinical and translational research.
DOI: 10.3389/fragi.2026.17685662026-03-09
Duraisamy Kempuraj, Prathiv Raj Ramesh Babu, Nithura Jayakumar, Mohit G. Belur, Charles H. Cohan, Arjun Sharma, Estella Sanchez-Guerrero, Tristin Anderson, Daniel Kong, Baskaran Chinnappan, Claudia Pena, Nancy G. Klimas, Theoharis C. Theoharides
Senescence is the biological aging associated with the gradual deterioration of cells and functions of various organs over time. This irreversible process is caused by genetic, metabolic, and environmental factors, such as telomere shortening, exposure to cytotoxic substances, and accumulated cellular damage over time, although the rate of degradation can be modified by lifestyle factors. Immunosenescence specifically refers to senescent changes in the innate and adaptive immunity and is associated with low inflammation known as inflammaging. As immunosenescence implies, reduced immune function leads to impaired tissue function and an increased risk of infection and heightened susceptibility to chronic, autoimmune, and neurodegenerative disorders, such as Alzheimer’s disease (AD) in the elderly. An increase in senescent cells is common in aging, which leads to age-associated diseases. Cellular senescence may also contribute to the onset and severity of Parkinson’s disease (PD) neuropathology. Inflammaging with high levels of proinflammatory marker expression may result from changes in immune responses, chronic antigenic stimulation, and senescence-associated secretory phenotype (SASP) factors, such as increased expression of interleukin-6 (IL-6), insulin-like growth factor binding proteins (IGFBPs), transforming growth factor-beta (TGF-β) and matrix metalloproteinase-10 (MMP-10) has been reported in AD patients. The levels of the senescence marker p16INK4a and several SASP factors, such as MMP-3, IL-6, IL-1α and IL-8 are elevated along with low levels of astrocytic lamin B1 in the substantia nigra of PD. This review discusses recent developments in neurosenescence and immunosenescence in AD and PD, as well as potential senolytic therapies.
DOI: 10.3389/fragi.2026.1756670