Age-Related ECM Stiffness Mediates TRAIL Activation in Muscle Stem Cell Differentiation.

The stiffening of the extracellular matrix (ECM) with age hinders muscle regeneration by causing intrinsic muscle stem cell (MuSC) dysfunction through a poorly understood mechanism. Here, the study aims to study those age-related molecular changes in the differentiation of MuSCs due to age and/or stiffness. Hence, young and aged MuSCs are seeded onto substrates engineered to mimic a soft and stiff ECM microenvironment to study those molecular changes using single-cell RNA sequencing (scRNA).

Mitigating skeletal muscle wasting in unloading and augmenting subsequent recovery.

Skeletal muscle wasting is the hallmark pathophysiological adaptation to unloading or disuse that demonstrates the dependency on frequent mechanical stimulation (e.g. muscle activation and subsequent loading) for homeostasis of normally load-bearing muscles.

Circulating extracellular vesicle characteristics differ between men and women following 12 weeks of concurrent exercise training.

Concurrent resistance and endurance exercise training (CET) has well-studied benefits; however, inherent hormonal and genetic differences alter adaptive responses to exercise between sexes. Extracellular vesicles (EVs) are factors that contribute to adaptive signaling. Our purpose was to test if EV characteristics differ between men and women following CET.

Network-based cytokine inference implicates Oncostatin M as a driver of an inflammation phenotype in knee osteoarthritis.

Inflammatory cytokines released by synovium after trauma disturb the gene regulatory network and have been implicated in the pathophysiology of osteoarthritis. A mechanistic understanding of how aging perturbs this process can help identify novel interventions. Here, we introduced network paradigms to simulate cytokine-mediated pathological communication between the synovium and cartilage.

Network-based systematic dissection of exercise-induced inhibition of myosteatosis in older individuals.

Accumulated fat in skeletal muscle (i.e. myosteatosis), common in sedentary older individuals, compromises skeletal muscle health and function.

Female aging: when translational models don't translate.

For many pathologies associated with aging, female patients present with higher morbidity and more frequent adverse events from treatments compared to male patients. While preclinical models are the foundation of our mechanistic understanding of age-related diseases, the most common models fail to recapitulate archetypical female aging trajectories. For example, while over 70% of the top age-related diseases are influenced by the systemic effects of reproductive senescence, we found that preclinical studies that include menopausal phenotypes modeling those seen in humans make up <1% of published aging biology research.

Nanotopographical Cues Tune the Therapeutic Potential of Extracellular Vesicles for the Treatment of Aged Skeletal Muscle Injuries.

Skeletal muscle regeneration relies on the tightly temporally regulated lineage progression of muscle stem/progenitor cells (MPCs) from activation to proliferation and, finally, differentiation. However, with aging, MPC lineage progression is disrupted and delayed, ultimately causing impaired muscle regeneration. Extracellular vesicles (EVs) have attracted broad attention as next-generation therapeutics for promoting tissue regeneration.

Extracellular Vesicles in Young Serum Contribute to the Restoration of Age-Related Brain Transcriptomes and Cognition in Old Mice.

We have previously demonstrated that circulating extracellular vesicles (EVs) are essential to the beneficial effect of young serum on the skeletal muscle regenerative cascade. Here, we show that infusions of young serum significantly improve age-associated memory deficits, and that these effects are abolished after serum depletion of EVs. RNA-seq analysis of the choroid plexus demonstrates EV-mediated effects on genes involved in barrier function and trans-barrier transport.

Arsenic disrupts extracellular vesicle-mediated signaling in regenerating myofibers.

Chronic exposure to environmental arsenic is a public health crisis affecting hundreds of millions of individuals worldwide. Though arsenic is known to contribute to many pathologies and diseases, including cancers, cardiovascular and pulmonary diseases, and neurological impairment, the mechanisms for arsenic-promoted disease remain unresolved. This is especially true for arsenic impacts on skeletal muscle function and metabolism, despite the crucial role that skeletal muscle health plays in maintaining cardiovascular health, systemic homeostasis, and cognition.

Change in circulating klotho in response to weight loss, with and without exercise, in adults with overweight or obesity.

Klotho is a protein associated with protection from aging-related diseases and health conditions. Obesity is associated with lower Klotho concentrations. Thus, this secondary analysis of adults with obesity examined 1) the change in serum Klotho concentration in response to a behavioral weight loss intervention by the magnitude of weight loss achieved; and 2) the association among serum Klotho concentration and weight, body composition, and cardiorespiratory fitness.

Exercise-primed extracellular vesicles improve cell-matrix adhesion and chondrocyte health.

Extracellular vesicles (EVs) have been suggested to transmit the health-promoting effects of exercise throughout the body. Yet, the mechanisms by which beneficial information is transmitted from extracellular vesicles to recipient cells are poorly understood, precluding a holistic understanding of how exercise promotes cellular and tissue health. In this study, using articular cartilage as a model, we introduced a network medicine paradigm to simulate how exercise facilitates communication between circulating EVs and chondrocytes, the cells resident in articular cartilage.

Dynamical modeling reveals RNA decay mediates the effect of matrix stiffness on aged muscle stem cell fate.

Loss of muscle stem cell (MuSC) self-renewal with aging reflects a combination of influences from the intracellular (e.g., post-transcriptional modifications) and extracellular (e.

Bioengineered 3D Skeletal Muscle Model Reveals Complement 4b as a Cell-Autonomous Mechanism of Impaired Regeneration with Aging.

A mechanistic understanding of cell-autonomous skeletal muscle changes after injury can lead to novel interventions to improve functional recovery in an aged population. However, major knowledge gaps persist owing to limitations of traditional biological aging models. 2D cell culture represents an artificial environment, while aging mammalian models are contaminated by influences from non-muscle cells and other organs.

Age-related matrix stiffening epigenetically regulates α-Klotho expression and compromises chondrocyte integrity.

Extracellular matrix stiffening is a quintessential feature of cartilage aging, a leading cause of knee osteoarthritis. Yet, the downstream molecular and cellular consequences of age-related biophysical alterations are poorly understood. Here, we show that epigenetic regulation of α-Klotho represents a novel mechanosensitive mechanism by which the aged extracellular matrix influences chondrocyte physiology.

Aging Affects the Efficacy of Platelet-Rich Plasma Treatment for Osteoarthritis.

Objective: Despite the increased use of platelet-rich plasma in the treatment of osteoarthritis, whether and how age of the platelet-rich plasma donor affects therapeutic efficacy is unclear.

Design: In vitro, male osteoarthritic human chondrocytes were treated with platelet-rich plasma from young (18-35 yrs) or old (≥65 yrs) donors, and the chondrogenic profile was evaluated using immunofluorescent staining for two markers of chondrogenicity, type II collagen and SOX-9. In vivo, we used a within-subjects design to compare Osteoarthritis Research Society International scores in aged mouse knee joints injected with platelet-rich plasma from young or old individuals.

Resistance exercise differentially alters extracellular vesicle size and subpopulation characteristics in healthy men and women: an observational cohort study.

Extracellular vesicles (EVs) are established mediators of adaptation to exercise. Currently, there are no published data comparing changes in EVs between men and women after resistance exercise. We tested the hypothesis that EV profiles would demonstrate a sex-specific signature following resistance exercise.

Neuroendocrine, inflammatory, and extracellular vesicle responses during the Navy Special Warfare Screener Selection Course.

Military operational stress is known to increase adrenal hormones and inflammatory cytokines, while decreasing hormones associated with the anabolic milieu and neuroendocrine system. Less is known about the role of extracellular vesicles (EVs), a form of cell-to-cell communication, in military operational stress and their relationship to circulating hormones. The purpose of this study was to characterize the neuroendocrine, cytokine, and EV response to an intense.

Utility of extracellular vesicles as a potential biological indicator of physiological resilience during military operational stress.

Extracellular vesicles (EVs) transport biological content between cells to mediate physiological processes. The association between EVs and resilience, the ability to cope with stress, is unknown. Using unbiased machine learning approaches, we aimed to identify a biological profile of resilience.