Physical activity, cathepsin B, and cognitive health.

Regular physical activity (PA) is beneficial for cognitive health, and cathepsin B (CTSB) - a protease released by skeletal muscle during PA - acts as a potential molecular mediator of this association. PA-induced metabolic and mechanical stress appears to increase plasma/serum CTSB levels. CTSB facilitates neurogenesis and synaptic plasticity in brain regions (e.

Mechanistic Insights Into the Exercise-Induced Changes in Muscle Lipids and Insulin Sensitivity-Expanding on the "Athlete's Paradox": Revisiting a 2011 Diabetes Classic by Amati et al.

Endurance exercise is widely recognized for its role in mitigating insulin resistance, yet the precise mechanisms remain unclear. In this Classics in Diabetes article, we revisit the article by Amati et al., "Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance: Another Paradox in Endurance-Trained Athletes?" Published in the October 2011 issue of Diabetes, this article was among the first to highlight the nuanced roles of exercise-induced changes in bioactive lipids such as ceramide and diacylglycerol (DAG) in insulin signaling.

Poor muscle quality: A hidden and detrimental health condition in obesity.

Poor muscle quality (MQ) is a hidden health condition in obesity, commonly disregarded and underdiagnosed, associated with poor health-related outcomes. This narrative review provides an in-depth exploration of MQ in obesity, including definitions, available assessment methods and challenges, pathophysiology, association with health outcomes, and potential interventions. MQ is a broad term that can include imaging, histological, functional, or metabolic assessments, evaluating beyond muscle quantity.

Greater recalled pain and movement-evoked pain are associated with longer 400-meter walk and repeat stair climb time: the Study of Muscle, Mobility and Aging.

Background: Musculoskeletal pain frequently accompanies the development of mobility disability and falls in old age. To better understand this, we aimed to quantify the impact of different pain measures-recalled pain and movement-evoked pain-on 400-meter walk and stair climb time in older adults participating in the Study of Muscle, Mobility and Aging (SOMMA).

Methods: In SOMMA (N=879, age=76.

Sex differences in the association between skeletal muscle energetics and perceived physical fatigability: the Study of Muscle, Mobility and Aging (SOMMA).

Greater perceived physical fatigability and lower skeletal muscle energetics are both predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of in vivo (maximal ATP production, ATPmax) and ex vivo (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher = greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher = greater) after a slow treadmill walk.

Insulin sensitivity and skeletal muscle mitochondrial respiration in Black and White women with obesity.

Objectives: Non-Hispanic black women (BW) have a greater risk of type 2 diabetes (T2D) and insulin resistance (IR) compared to non-Hispanic white women (WW). The mechanisms leading to these differences are not understood, and it is unclear whether synergistic effects of race and obesity impact disease risk. To understand the interaction of race and weight, hepatic and peripheral IR were compared in WW and BW with and without obesity.

Harmonization of experimental procedures to assess mitochondrial respiration in human permeabilized skeletal muscle fibers.

Aim: High-resolution respirometry in human permeabilized muscle fibers is extensively used for analysis of mitochondrial adaptions to nutrition and exercise interventions, and is linked to athletic performance. However, the lack of standardization of experimental conditions limits quantitative inter- and intra-laboratory comparisons.

Methods: In our study, an international team of investigators measured mitochondrial respiration of permeabilized muscle fibers obtained from three biopsies (vastus lateralis) from the same healthy volunteer to avoid inter-individual variability.

Role of Walking Energetics and Perceived Fatigability Differs by Gait Speed: The Study of Muscle, Mobility and Aging (SOMMA).

Background: Slower gait speed may be driven by greater energy deficits and fatigability among older adults. We examined associations of walking energetics and perceived physical fatigability with gait speed among slower and faster walkers. Additionally, we used statistical mediation to examine the role of fatigability in the associations of walking energetics and gait speed using the Study of Muscle, Mobility and Aging (SOMMA).

Skeletal Muscle Composition, Power, and Mitochondrial Energetics in Older Men and Women With Knee Osteoarthritis.

Objective: Our objective was to investigate the overall and sex-specific relationships between the presence and severity of knee osteoarthritis (KOA) and muscle composition, power, and energetics in older adults.

Methods: Male and female patients (n = 655, mean ± SD age 76.1 ± 4.

Sex Differences in the Association between Skeletal Muscle Energetics and Perceived Physical Fatigability: The Study of Muscle, Mobility and Aging (SOMMA).

Greater perceived physical fatigability and lower skeletal muscle energetics are predictors of mobility decline. Characterizing associations between muscle energetics and perceived fatigability may provide insight into potential targets to prevent mobility decline. We examined associations of (maximal ATP production, ATPmax) and (maximal carbohydrate supported oxidative phosphorylation [max OXPHOS] and maximal fatty acid supported OXPHOS [max FAO OXPHOS]) measures of mitochondrial energetics with two measures of perceived physical fatigability, Pittsburgh Fatigability Scale (PFS, 0-50, higher=greater) and Rating of Perceived Exertion (RPE Fatigability, 6-20, higher=greater) after a slow treadmill walk.

Associations between regional adipose tissue distribution and skeletal muscle bioenergetics in older men and women.

Objective: The aim of this study was to examine associations of ectopic adipose tissue (AT) with skeletal muscle (SM) mitochondrial bioenergetics in older adults.

Methods: Cross-sectional data from 829 adults ≥70 years of age were used. Abdominal, subcutaneous, and visceral AT and thigh muscle fat infiltration (MFI) were quantified by magnetic resonance imaging.

Isolation of Nuclei from Human Intermuscular Adipose Tissue and Downstream Single-Nuclei RNA Sequencing.

Intermuscular adipose tissue (IMAT) is a relatively understudied adipose depot located between muscle fibers. IMAT content increases with age and BMI and is associated with metabolic and muscle degenerative diseases; however, an understanding of the biological properties of IMAT and its interplay with the surrounding muscle fibers is severely lacking. In recent years, single-cell and nuclei RNA sequencing have provided us with cell type-specific atlases of several human tissues.

The mitochondrial multi-omic response to exercise training across rat tissues.

Mitochondria have diverse functions critical to whole-body metabolic homeostasis. Endurance training alters mitochondrial activity, but systematic characterization of these adaptations is lacking. Here, the Molecular Transducers of Physical Activity Consortium mapped the temporal, multi-omic changes in mitochondrial analytes across 19 tissues in male and female rats trained for 1, 2, 4, or 8 weeks.

Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity.

Muscle Mitochondrial Bioenergetic Capacities Are Associated With Multimorbidity Burden in Older Adults: The Study of Muscle, Mobility and Aging.

Background: The geroscience hypothesis posits that aging biological processes contribute to many age-related deficits, including the accumulation of multiple chronic diseases. Though only one facet of mitochondrial function, declines in muscle mitochondrial bioenergetic capacities may contribute to this increased susceptibility to multimorbidity.

Methods: The Study of Muscle, Mobility and Aging (SOMMA) assessed ex vivo muscle mitochondrial energetics in 764 older adults (mean age = 76.

Cardiopulmonary Exercise Testing in a Prospective Multicenter Cohort of Older Adults.

Purpose: Cardiorespiratory fitness (CRF) measured by peak oxygen consumption (V̇O 2peak ) declines with aging and correlates with mortality and morbidity. Cardiopulmonary exercise testing (CPET) is the criterion method to assess CRF, but its feasibility, validity, and reliability in older adults are unclear. Our objective was to design and implement a dependable, safe, and reliable CPET protocol in older adults.

Role of Cardiorespiratory Fitness and Mitochondrial Oxidative Capacity in Reduced Walk Speed of Older Adults With Diabetes.

Cardiorespiratory fitness and mitochondrial oxidative capacity are associated with reduced walking speed in older adults, but their impact on walking speed in older adults with diabetes has not been clearly defined. We examined differences in cardiorespiratory fitness and skeletal muscle mitochondrial oxidative capacity between older adults with and without diabetes, as well as determined their relative contribution to slower walking speed in older adults with diabetes. Participants with diabetes (n = 159) had lower cardiorespiratory fitness and mitochondrial respiration in permeabilized fiber bundles compared with those without diabetes (n = 717), following adjustments for covariates including BMI, chronic comorbid health conditions, and physical activity.

Associations Between D3Cr Muscle Mass and Magnetic Resonance Thigh Muscle Volume With Strength, Power, Physical Performance, Fitness, and Limitations in Older Adults in the SOMMA Study.

Background: How magnetic resonance (MR) derived thigh muscle volume and deuterated creatine dilution derived muscle mass (D3Cr muscle mass) differentially relate to strength, fitness, and other functions in older adults-and whether associations vary by sex-is not known.

Methods: Men (N = 345) and women (N = 482) aged ≥70 years from the Study of Muscle, Mobility, and Aging completed leg extension strength (1-repetition max) and cardiopulmonary exercise testing to assess fitness (VO2peak). Correlations and adjusted regression models stratified by sex were used to assess the association between muscle size measures, study outcomes, and sex interactions.

Associations of Skeletal Muscle Mass, Muscle Fat Infiltration, Mitochondrial Energetics, and Cardiorespiratory Fitness With Liver Fat Among Older Adults.

Background: Muscle mass loss may be associated with liver fat accumulation, yet scientific consensus is lacking and evidence in older adults is scant. It is unclear which muscle characteristics might contribute to this association in older adults.

Methods: We associated comprehensive muscle-related phenotypes including muscle mass normalized to body weight (D3-creatine dilution), muscle fat infiltration (magnetic resonance imaging), carbohydrate-supported muscle mitochondrial maximal oxidative phosphorylation (respirometry), and cardiorespiratory fitness (VO2 peak) with liver fat among older adults.

Associations of accelerometry-measured and self-reported physical activity and sedentary behavior with skeletal muscle energetics: The Study of Muscle, Mobility and Aging (SOMMA).

Background: Skeletal muscle energetics decline with age, and physical activity (PA) has been shown to offset these declines in older adults. Yet, many studies reporting these effects were based on self-reported PA or structured exercise interventions. Therefore, we examined the associations of accelerometry-measured and self-reported PA and sedentary behavior (SB) with skeletal muscle energetics and explored the extent to which PA and sedentary behavior would attenuate the associations of age with muscle energetics.

Signatures of cysteine oxidation on muscle structural and contractile proteins are associated with physical performance and muscle function in older adults: Study of Muscle, Mobility and Aging (SOMMA).

Oxidative stress is considered a contributor to declining muscle function and mobility during aging; however, the underlying molecular mechanisms remain poorly described. We hypothesized that greater levels of cysteine (Cys) oxidation on muscle proteins are associated with decreased measures of mobility. Herein, we applied a novel redox proteomics approach to measure reversible protein Cys oxidation in vastus lateralis muscle biopsies collected from 56 subjects in the Study of Muscle, Mobility and Aging (SOMMA), a community-based cohort study of individuals aged 70 years and older.

Energetics and clinical factors for the time required to walk 400 m: The Study of Muscle, Mobility and Aging (SOMMA).

Background: Walking slows with aging often leading to mobility disability. Mitochondrial energetics has been found to be associated with gait speed over short distances. Additionally, walking is a complex activity but few clinical factors that may be associated with walk time have been studied.