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 = 76.4, 56.5% women, and 85.9% non-Hispanic White) by high-resolution respirometry of permeabilized muscle fibers. We estimated the proportional odds ratio (POR [95% CI]) for the likelihood of greater multimorbidity (4 levels: 0 conditions, N = 332; 1 condition, N = 299; 2 conditions, N = 98; or 3+ conditions, N = 35) from an index of 11 conditions, per SD decrement in muscle mitochondrial energetic parameters. Distribution of conditions allowed for testing the associations of maximal muscle energetics with some individual conditions.
RESULTS: Lower oxidative phosphorylation supported by fatty acids and/or complex I- and II-linked carbohydrates (eg, Max OXPHOSCI+CII) was associated with a greater multimorbidity index score (POR = 1.32 [1.13, 1.54]) and separately with diabetes mellitus (OR = 1.62 [1.26, 2.09]), depressive symptoms (OR = 1.45 [1.04, 2.00]) and possibly chronic kidney disease (OR = 1.57 [0.98, 2.52]) but not significantly with other conditions (eg, cardiac arrhythmia, chronic obstructive pulmonary disease).
CONCLUSIONS: Lower muscle mitochondrial bioenergetic capacities were associated with a worse composite multimorbidity index score. Our results suggest that decrements in muscle mitochondrial energetics may contribute to a greater global burden of disease and are more strongly related to some conditions than others.

Calcium research, since its pivotal discovery in the early 1800s through the heating of limestone, has led to the identification of its multi-functional roles. These include its functions as a reducing agent in chemical processes, structural properties in shells and bones, and significant role in cells relating to this review: cellular signaling. Calcium signaling involves the movement of calcium ions within or between cells, which can affect the electrochemical gradients between intra- and extracellular membranes, ligand binding, enzyme activity, and other mechanisms that determine cell fate. Calcium signaling in muscle, as elucidated by the sliding filament model, plays a significant role in muscle contraction. However, as organisms age, alterations occur within muscle tissue. These changes include sarcopenia, loss of neuromuscular junctions, and changes in mineral concentration, all of which have implications for calcium\'s role. Additionally, a field of study that has gained recent attention, cellular senescence, is associated with aging and disturbed calcium homeostasis, and is thought to affect sarcopenia progression. Changes seen in calcium upon aging may also be influenced by its crosstalk with other minerals such as iron and zinc. This review investigates the role of calcium signaling in aging muscle and cellular senescence. We also aim to elucidate the interactions among calcium, iron, and zinc across various cells and conditions, ultimately deepening our understanding of calcium signaling in muscle aging.

OBJECTIVE: Implement STEAM-DTI to model time-dependent diffusion eigenvalues using the random permeable barrier model (RPBM) to study age-related differences in the medial gastrocnemius (MG) muscle. Validate diffusion model-extracted fiber diameter for histological assessment.
METHODS: Diffusion imaging at different diffusion times (Δ) was performed on seven young and six senior participants. Time-dependent diffusion eigenvalues (λ2 (t), λ3 (t), and D⊥ (t); average of λ2 (t) and λ3 (t)) were fit to the RPBM to extract tissue microstructure parameters. Biopsy of the MG tissue for histological assessment was performed on a subset of participants (four young, six senior).
RESULTS: λ3 (t) was significantly higher in the senior cohort for the range of diffusion times. RPBM fits to λ2 (t) yielded fiber diameters in agreement to those from histology for both cohorts. The senior cohort had lower values of volume fraction of membranes, ζ, in fits to λ2 (t), λ3 (t), and D⊥ (t) (significant for fit to λ3 (t)). Fits of fiber diameter from RPBM to that from histology had the highest correlation for the fit to λ2 (t).
CONCLUSIONS: The age-related patterns in λ2 (t) and λ3 (t) could tentatively be explained from RPBM fits; these patterns may potentially arise from a decrease in fiber asymmetry and an increase in permeability with age.

UNASSIGNED: Identify contributors to differences in the muscle size and strength of sedentary and active young and middle-aged adults.
UNASSIGNED: This cross-sectional study included 98 participants aged 20-65 years. Participants were categorized based on age and self-reported physical activity (PA) habits. Participants completed a strength assessment of knee extensors (KEPT), knee flexors (KFPT), plantar flexors (PFPT), and dorsiflexors (DFPT), a 3-day dietary intake log, 7-day accelerometry, and a magnetic resonance imaging (MRI) scan for muscle cross-sectional area analysis of the right quadriceps (CSAq).
UNASSIGNED: There were significant age and activity-related group effects for relative protein intake (p<0.001), relative energy intake (p=0.04), KEPT (p=0.01), CSAq (p=0.002), PFPT (p=0.004) and DFPT (p=0.003). Moderate, moderate-to-vigorous, and vigorous PA were positively associated with CSAq (R2=0.69- 0.71; p<0.05), KEPT (R2=0.61-0.63; p<0.05), and PFPT (R2=0.31-0.36; p<0.05). Relative protein intake and daily leucine intake were significantly and positively associated with CSAq (R2=0.70 and 0.67 respectively; p<0.05), KEPT (R2=0.62 and 0.65 respectively; p<0.05), and PFPT (R2=0.29 and 0.28 respectively; p<0.05).
UNASSIGNED: Muscle size and strength were lower in middle age relative to younger age, but increased PA, protein intake, and leucine intake was associated with the preservation of muscle size and strength in larger muscle groups of the lower body.

BACKGROUND: Aging leads to loss of skeletal muscle, diminished muscle strength, and decline in physical functions.
OBJECTIVE: This study evaluates Withania somnifera and some dietary interventions to combat muscle weakness in aging rats.
METHODS: Rats (12-13 months old) corresponding to a human age of 60-65 years were assigned to various groups and given orally a standardized W. somnifera extract (WSE, 500 mg/kg) or a protein cocktail comprising soybean (1.5 g/kg) and quinoa (1 g/kg) or a combination of WSE and the protein cocktail or whey protein (1 g/kg) as a reference standard or only resistance exercise for 60 days. Grip strength and blood glucose levels were monitored weekly. At the end of the treatment, total protein, inflammatory markers (CRP, IL-6 and TNF-α), AMPK, malondialdehyde, glutathione, antioxidant enzymes and apoptotic regulator genes (Bax and Bcl-2) were assayed. The biceps brachii muscle of all animals was subjected to histomorphological study.
RESULTS: All treatments successfully attenuated aging-elevated glucose, CRP, IL-6, TNF-α, AMPK, malondialdehyde, and Bax levels. A significant restoration of the aging-depleted total protein levels, glutathione, superoxide dismutase, catalase, and Bcl-2 was noted in the treatment groups. An increase in grip strength and greater biceps mass with all treatments indicated regaining of the frail aging muscle\'s strength and functionality. The WSE + protein treatment elicited the best results among all treatment groups to optimize muscle strength.
CONCLUSIONS: All the interventions curbed muscle loss and strengthened the skeletal muscle by reducing inflammation, oxidative stress and apoptosis, and increasing ATP availability to the muscle.

Studying aging is important to further understand the molecular mechanisms underlying this physiological process and, ideally, to identify a panel of aging biomarkers. Animals, in particular mice, are often used in aging studies, since they mimic important features of human aging, age quickly, and are easy to manipulate. The present work describes the use of Fourier Transform Infrared (FTIR) spectroscopy to identify an age-related spectroscopic profile of the cardiac and skeletal muscle tissues of C57BL/6J female mice. We acquired ATR-FTIR spectra of cardiac and skeletal muscle at four different ages: 6; 12; 17 and 24 months (10 samples at each age) and analyzed the data using multivariate statistical tools (PCA and PLS) and peak intensity analyses. The results suggest deep changes in protein secondary structure in 24-month-old mice compared to both tissues in 6-month-old mice. Oligomeric structures decreased with age in both tissues, while intermolecular β-sheet structures increased with aging in cardiac muscle but not in skeletal muscle. Despite FTIR spectroscopy being unable to identify the proteins responsible for these conformational changes, this study gives insights into the potential of FTIR to monitor the aging process and identify an age-specific spectroscopic signature.

Skeletal muscle atrophy in an inevitable occurrence with advancing age, and a consequence of disease including cancer. Muscle atrophy in the elderly is managed by a regimen of resistance exercise and increased protein intake. Understanding the signaling that regulates muscle mass may identify potential therapeutic targets for the prevention and reversal of muscle atrophy in metabolic and neuromuscular diseases. This review covers the major anabolic and catabolic pathways that regulate skeletal muscle mass, with a focus on recent progress and potential new players.

3D strain or strain rate tensor mapping comprehensively captures regional muscle deformation. While compressive strain along the muscle fiber is a potential measure of the force generated, radial strains in the fiber cross-section may provide information on the material properties of the extracellular matrix. Additionally, shear strain may potentially inform on the shearing of the extracellular matrix; the latter has been hypothesized as the mechanism of lateral transmission of force. Here, we implement a novel fast MR method for velocity mapping to acquire multi-slice images at different % maximum voluntary contraction (MVC) for 3D strain mapping to explore deformation in the plantar-flexors under isometric contraction in a cohort of young and senior subjects. 3D strain rate and strain tensors were computed and eigenvalues and two invariants (maximum shear and volumetric strain) were extracted. Strain and strain rate indices (contractile and in-plane strain/strain rate, shear strain/strain rate) changed significantly with %MVC (30 and 60% MVC) and contractile and shear strain with age in the medial gastrocnemius. In the soleus, significant differences with age in contractile and shear strain were seen. Univariate regression revealed weak but significant correlation of in-plane and shear strain and shear strain rate indices to %MVC and correlation of contractile and shear strain indices to force. The ability to map strain tensor components provides unique insights into muscle physiology: with contractile strain providing an index of the force generated by the muscle fibers while the shear strain could potentially be a marker of lateral transmission of force.

Fortetropin is a proteo-lipid complex made from fertilized egg yolk and, in young men, has been shown to increase lean body mass.
The purpose of this study was to examine the effects of 21 days of Fortetropin supplementation on the fractional synthetic rate (FSR) of muscle protein in 10 healthy, older men and 10 women (66.4 ± 4.5 y). We used 2H2O labeling to measure FSR of multiple muscle protein ontologies. D3-creatine dilution was used to determine muscle mass at baseline. Subjects ingested 70% 2H2O for 21 day and saliva samples were collected to determine body 2H2O enrichment. A microbiopsy was obtained from the m. vastus lateralis on Day 21. Subjects were randomly assigned to Fortetropin (19.8 g/d) or placebo (cheese powder, 19.8 g/d).
Restricting kinetic data to proteins with ≥2 peptides measured in at least 4 subjects per group resulted in 117 proteins meeting these criteria. The mean FSR for a majority of proteins in several muscle gene ontologies was higher in the Fortetropin group compared to placebo (32/38 myofibril proteins, 33/44 sarcoplasmic proteins, and 12/17 mitochondrial proteins) and this proportion was significantly different between groups using a binomial test and were independent of sex or baseline muscle mass.
The overall magnitude of the difference in muscle protein FSR of Fortetropin from placebo was 18%, with multiple gene ontologies affected. While these results should be confirmed in larger cohorts, they suggest that Fortetropin supplementation is effective for promoting muscle protein synthesis in older people.

More than half a century of skeletal muscle research is continuing at Padua University (Italy) under the auspices of the Interdepartmental Research Centre of Myology (CIR-Myo), the European Journal of Translational Myology (EJTM) and recently also with the support of the A&CM-C Foundation for Translational Myology, Padova, Italy. The Volume 30(1), 2020 of the EJTM opens with the collection of abstracts for the conference \"2020 Padua Muscle Days: Mobility Medicine 30 years of Translational Research\". This is an international conference that will be held between March 18-21, 2020 in Euganei Hills and Padova in Italy. The abstracts are excellent examples of translational research and of the multidimensional approaches that are needed to classify and manage (in both the acute and chronic phases) diseases of Mobility that span from neurologic, metabolic and traumatic syndromes to the biological process of aging. One of the typical aim of Physical Medicine and Rehabilitation is indeed to reduce pain and increase mobility enough to enable impaired persons to walk freely, garden, and drive again. The excellent contents of this Collection of Abstracts reflect the high scientific caliber of researchers and clinicians who are eager to present their results at the PaduaMuscleDays. A series of EJTM Communications will also add to this preliminary evidence.