Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats.

Mitochondrial genomic integrity is a key element of physiological processes and health. Changes in the half-life of the mitochondrial genome are implicated in the generation and accumulation of age-induced mitochondrial DNA (mtDNA) mutations, which are implicated in skeletal muscle aging and sarcopenia. There are conflicting data on the half-life of mtDNA, and there is limited information on how aging affects half-life in skeletal muscle.

Running Economy Changes Alter Predicted Running Speed and Performance in Collegiate Runners.

The goal of the study was to determine the effect of altering running strategy on predicted running performance in distance runners through application of a novel prediction model. Fifteen male ( = 10; Age: 22.2 ± 4.

Non-transgenic guinea pig strains exhibit divergent age-related changes in hippocampal mitochondrial respiration.

Aim: Alzheimer's disease (AD) is the most common form of dementia. However, while 150+ animal models of AD exist, drug translation from preclinical models to humans for treatment usually fails. One factor contributing to low translation is likely the absence of neurodegenerative models that also encompass the multi-morbidities of human aging.

Three-dimensional imaging studies in mice identify cellular dynamics of skeletal muscle regeneration.

The function of many organs, including skeletal muscle, depends on their three-dimensional structure. Muscle regeneration therefore requires not only reestablishment of myofibers but also restoration of tissue architecture. Resident muscle stem cells (SCs) are essential for regeneration, but how SCs regenerate muscle architecture is largely unknown.

A practical perspective on how to develop, implement, execute, and reproduce high-resolution respirometry experiments: The physiologist's guide to an Oroboros O2k.

The development of high-resolution respirometry (HRR) has greatly expanded the analytical scope to study mitochondrial respiratory control relative to specific tissue/cell types across various metabolic states. Specifically, the Oroboros Oxygraph 2000 (O2k) is a common tool for measuring rates of mitochondrial respiration and is the focus of this perspective. The O2k platform is amenable for answering numerous bioenergetic questions.

Phytochemical compound PB125 attenuates skeletal muscle mitochondrial dysfunction and impaired proteostasis in a model of musculoskeletal decline.

Impaired mitochondrial function and disrupted proteostasis contribute to musculoskeletal dysfunction. However, few interventions simultaneously target these two drivers to prevent musculoskeletal decline. Nuclear factor erythroid 2-related factor 2 (Nrf2) activates a transcriptional programme promoting cytoprotection, metabolism, and proteostasis.

Nontransgenic Guinea Pig Strains Exhibit Hallmarks of Human Brain Aging and Alzheimer's Disease.

Older age is the primary risk factor for most chronic diseases, including Alzheimer's disease (AD). Current preclinical models to study brain aging and AD are mainly transgenic and harbor mutations intended to mirror brain pathologies associated with human brain aging/AD (eg, by increasing production of the amyloid precursor protein, amyloid beta [Aβ], and/or phosphorylated tau, all of which are key pathological mediators of AD). Although these models may provide insight on pathophysiological processes in AD, none completely recapitulate the disease and its strong age-dependence, and there has been limited success in translating preclinical results and treatments to humans.

The Dunkin Hartley Guinea Pig Is a Model of Primary Osteoarthritis That Also Exhibits Early Onset Myofiber Remodeling That Resembles Human Musculoskeletal Aging.

Skeletal muscle dysfunction, articular cartilage degeneration, and bone loss occur essentially in parallel during aging. Mechanisms contributing to this systemic musculoskeletal decline remain incompletely understood, limiting progress toward developing effective therapeutics. Because the progression of human musculoskeletal aging is slow, researchers rely on rodent models to identify mechanisms and test interventions.

Sex differences in changes of protein synthesis with rapamycin treatment are minimized when metformin is added to rapamycin.

Loss of protein homeostasis is a hallmark of the aging process. We and others have previously shown that maintenance of proteostasis is a shared characteristic of slowed-aging models. Rapamycin (Rap) exerts sex-specific effects on murine lifespan, but the combination of Rap with the anti-hyperglycemic drug metformin (Rap + Met) equally increases male and female mouse median lifespan.

Exercise-Induced Mitohormesis for the Maintenance of Skeletal Muscle and Healthspan Extension.

Oxidative damage is one mechanism linking aging with chronic diseases including the progressive loss of skeletal muscle mass and function called sarcopenia. Thus, mitigating oxidative damage is a potential avenue to prevent or delay the onset of chronic disease and/or extend healthspan. Mitochondrial hormesis (mitohormesis) occurs when acute exposure to stress stimulates adaptive mitochondrial responses that improve mitochondrial function and resistance to stress.

Muscle-specific changes in protein synthesis with aging and reloading after disuse atrophy.

Background: Successful strategies to halt or reverse sarcopenia require a basic understanding of the factors that cause muscle loss with age. Acute periods of muscle loss in older individuals have an incomplete recovery of muscle mass and strength, thus accelerating sarcopenic progression. The purpose of the current study was to further understand the mechanisms underlying the failure of old animals to completely recover muscle mass and function after a period of hindlimb unloading.

Six Weeks of Low-Load Blood Flow Restricted and High-Load Resistance Exercise Training Produce Similar Increases in Cumulative Myofibrillar Protein Synthesis and Ribosomal Biogenesis in Healthy Males.

High-load resistance exercise contributes to maintenance of muscle mass, muscle protein quality, and contractile function by stimulation of muscle protein synthesis (MPS), hypertrophy, and strength gains. However, high loading may not be feasible in several clinical populations. Low-load blood flow restricted resistance exercise (BFRRE) may provide an alternative approach.

Differential Effects of Rapamycin and Metformin in Combination With Rapamycin on Mechanisms of Proteostasis in Cultured Skeletal Myotubes.

mTOR inhibition extends life span in multiple organisms. In mice, when metformin treatment (Met) is added to the mTOR inhibitor rapamycin (Rap), median and maximal life span is extended to a greater degree than with Rap or Met alone. Treatments that extend life span often maintain proteostasis.

Mitochondria as a Target for Mitigating Sarcopenia.

Sarcopenia is the loss of muscle mass, strength, and physical function that is characteristic of aging. The progression of sarcopenia is gradual but may be accelerated by periods of muscle loss during physical inactivity secondary to illness or injury. The loss of mobility and independence and increased comorbidities associated with sarcopenia represent a major healthcare challenge for older adults.

Skeletal Muscle Mitochondrial Protein Synthesis and Respiration Increase With Low-Load Blood Flow Restricted as Well as High-Load Resistance Training.

It is well established that high-load resistance exercise (HLRE) can stimulate myofibrillar accretion. Additionally, recent studies suggest that HLRE can also stimulate mitochondrial biogenesis and respiratory function. However, in several clinical situations, the use of resistance exercise with high loading may not constitute a viable approach.

Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults.

Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and cardiorespiratory fitness.

Targeting mitochondrial function and proteostasis to mitigate dynapenia.

Traditionally, interventions to treat skeletal muscle aging have largely targeted sarcopenia-the age-related loss of skeletal muscle mass. Dynapenia refers to the age-related loss in skeletal muscle function due to factors outside of muscle mass, which helps to inform treatment strategies for aging skeletal muscle. There is evidence that mechanisms to maintain protein homeostasis and proteostasis, deteriorate with age.

Skeletal muscle mitochondrial protein synthesis and respiration in response to the energetic stress of an ultra-endurance race.

The 2016 Colorado Trail Race (CTR) was an ultra-endurance mountain bike race in which competitors cycled for up to 24 h/day between altitudes of 1,675 and 4,025 m to complete 800 km and 21,000 m of elevation gain. In one athlete, we had the unique opportunity to characterize skeletal muscle protein synthesis and mitochondrial respiration in response to a normal activity control period (CON) and the CTR. We hypothesized that mitochondrial protein synthesis would be elevated and mitochondrial respiration would be maintained during the extreme stresses of the CTR.

Influence of Nrf2 activators on subcellular skeletal muscle protein and DNA synthesis rates after 6 weeks of milk protein feeding in older adults.

In older adults, chronic oxidative and inflammatory stresses are associated with an impaired increase in skeletal muscle protein synthesis after acute anabolic stimuli. Conjugated linoleic acid (CLA) and Protandim have been shown to activate nuclear factor erythroid-derived 2-like 2 (Nrf2), a transcription factor for the antioxidant response element and anti-inflammatory pathways. This study tested the hypothesis that compared to a placebo control (CON), CLA and Protandim would increase skeletal muscle subcellular protein (myofibrillar, mitochondrial, cytoplasmic) and DNA synthesis in older adults after 6 weeks of milk protein feeding.