scholarly journals Nutritional Strategies to Counteract Mitochondrial Dysfunction and NAD+ Deficiency in Human Sarcopenia

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 764-765
Author(s):  
Jerome Feige
Keyword(s):  
Skeletal Muscle ◽  
Nicotinamide Riboside ◽  
Transcriptional Signature ◽  
Mitochondrial Homeostasis ◽  
Muscle Aging ◽  
Age Related ◽  
Genome Wide ◽  
Transcriptional Changes ◽  
Physical Autonomy ◽  
And Performance

Abstract The causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. We compared genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men of different ethnicity. Individuals with sarcopenia demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced bioenergetic activity, and NAD+ deficiency in sarcopenic muscle. Our results point to mitochondrial homeostasis as a key mediator of pathological muscle aging. Novel nutritional solutions enhancing muscle strength and performance by enhancing mitochondrial function are being tested clinically and will be reviewed. These include activating mitophagy with Urolithin A or restoring NAD+ levels via tryptophane/kynurenine or with nicotinamide riboside.

scholarly journals Mitochondrial oxidative capacity and NAD+ biosynthesis are reduced in human sarcopenia across ethnicities

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Eugenia Migliavacca ◽  
Stacey K. H. Tay ◽  
Harnish P. Patel ◽  
Tanja Sonntag ◽  
Gabriele Civiletto ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Oxidative Capacity ◽  
Molecular Profile ◽  
Transcriptional Signature ◽  
Age Related ◽  
Transcriptional Changes ◽  
Physical Autonomy ◽  
And Function

AbstractThe causes of impaired skeletal muscle mass and strength during aging are well-studied in healthy populations. Less is known on pathological age-related muscle wasting and weakness termed sarcopenia, which directly impacts physical autonomy and survival. Here, we compare genome-wide transcriptional changes of sarcopenia versus age-matched controls in muscle biopsies from 119 older men from Singapore, Hertfordshire UK and Jamaica. Individuals with sarcopenia reproducibly demonstrate a prominent transcriptional signature of mitochondrial bioenergetic dysfunction in skeletal muscle, with low PGC-1α/ERRα signalling, and downregulation of oxidative phosphorylation and mitochondrial proteostasis genes. These changes translate functionally into fewer mitochondria, reduced mitochondrial respiratory complex expression and activity, and low NAD+ levels through perturbed NAD+ biosynthesis and salvage in sarcopenic muscle. We provide an integrated molecular profile of human sarcopenia across ethnicities, demonstrating a fundamental role of altered mitochondrial metabolism in the pathological loss of skeletal muscle mass and function in older people.

scholarly journals Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

2020 ◽  
Vol 21 (15) ◽  
pp. 5236 ◽  
Author(s):  
Evelyn Ferri ◽  
Emanuele Marzetti ◽  
Riccardo Calvani ◽  
Anna Picca ◽  
Matteo Cesari ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cellular Senescence ◽  
Significant Loss ◽  
Muscle Aging ◽  
Age Related ◽  
Mitochondrial Functions ◽  
Health Quality ◽  
Skeletal Muscle Aging ◽  
And Function

Skeletal muscle aging is associated with a significant loss of skeletal muscle strength and power (i.e., dynapenia), muscle mass and quality of life, a phenomenon known as sarcopenia. This condition affects nearly one-third of the older population and is one of the main factors leading to negative health outcomes in geriatric patients. Notwithstanding the exact mechanisms responsible for sarcopenia are not fully understood, mitochondria have emerged as one of the central regulators of sarcopenia. In fact, there is a wide consensus on the assumption that the loss of mitochondrial integrity in myocytes is the main factor leading to muscle degeneration. Mitochondria are also key players in senescence. It has been largely proven that the modulation of mitochondrial functions can induce the death of senescent cells and that removal of senescent cells improves musculoskeletal health, quality, and function. In this review, the crosstalk among mitochondria, cellular senescence, and sarcopenia will be discussed with the aim to elucidate the role that the musculoskeletal cellular senescence may play in the onset of sarcopenia through the mediation of mitochondria.

scholarly journals The interaction between nutrition and exercise for promoting health and performance

2017 ◽  
Vol 77 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Oliver C. Witard ◽  
Derek Ball
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Metabolic Response ◽  
Healthy Ageing ◽  
Human Model ◽  
Health Issues ◽  
The Public ◽  
Non Invasive ◽  
Age Related ◽  
And Performance

The theme of The Nutrition Society Spring Conference 2017 was on the interaction between nutrition and exercise for promoting healthy ageing, maintaining cognitive function and improving the metabolic health of the population. The importance of this theme is highlighted by the public health issues surrounding obesity, diabetes and the age-related loss of skeletal muscle mass (sarcopenia). The opening symposium provided a historical perspective of both invasive and non-invasive methodologies for measuring exercise energetics and energy balance. Data derived from these techniques underpin current understanding regarding the metabolic response to nutrition and exercise. Further symposia examined the importance of skeletal muscle for healthy ageing in older men and postmenopausal women. From a nutritional perspective, the potential for animal- v. plant-based protein sources to offset the age-related decline in muscle mass was discussed. The day concluded by discussing the link(s) between nutrition, exercise and brain function. Day 2 commenced with examples of applied equine research illustrating the link between nutrition/exercise and insulin resistance to those of a human model. The final symposium examined the combined role of nutrition and exercise in reducing risk of type 2 diabetes and dyslipidaemia. The overall conclusion from the meeting was that the interaction between diet and physical activity confers greater benefits to human health and performance than either component alone.

scholarly journals Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

2021 ◽  
Author(s):  
Daniel J Ham ◽  
Anastasiya Boersch ◽  
Kathrin Chojnowska ◽  
Shuo Lin ◽  
Aurel B Leuchtmann ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calorie Restriction ◽  
Expression Profiles ◽  
Life Quality ◽  
Gene Expression Profiles ◽  
Nutrient Sensing ◽  
Skeletal Muscle Function ◽  
Muscle Gene Expression ◽  
Muscle Aging ◽  
Age Related

As global life expectancy continues to climb, maintaining skeletal muscle function is increasingly essential to ensure a good life quality for aging populations. Calorie restriction (CR) is the most potent and reproducible intervention to extend health and lifespan, but is largely unachievable in humans. Therefore, identification of 'CR mimetics' has received much attention. CR targets nutrient-sensing pathways centering on mTORC1. The mTORC1 inhibitor, rapamycin, has been proposed as a potential CR mimetic and is proven to counteract age-related muscle loss. Therefore, we tested whether rapamycin acts via similar mechanisms as CR to slow muscle aging. Contrary to our expectation, long-term CR and rapamycin-treated geriatric mice display distinct skeletal muscle gene expression profiles despite both conferring benefits to aging skeletal muscle. Furthermore, CR improved muscle integrity in a mouse with nutrient-insensitive sustained muscle mTORC1 activity and rapamycin provided additive benefits to CR in aging mouse muscles. Therefore, RM and CR exert distinct, compounding effects in aging skeletal muscle, opening the possibility of parallel interventions to counteract muscle aging.

scholarly journals Molecular Regulation and Rejuvenation of Muscle Stem (Satellite) Cell Aging

2015 ◽  
Vol 7 (2) ◽  
pp. 73
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Skeletal Muscle ◽  
Stem Cells ◽  
Stem Cell ◽  
Satellite Cell ◽  
Muscle Mass ◽  
Satellite Cells ◽  
Cell Function ◽  
Muscle Stem Cell ◽  
Muscle Aging ◽  
Age Related

BACKGROUND: Age-related muscle loss leads to lack of muscle strength, resulting in reduced posture and mobility and an increased risk of falls, all of which contribute to a decrease in quality of life. Skeletal muscle regeneration is a complex process, which is not yet completely understood.CONTENT: Skeletal muscle undergoes a progressive age-related loss in mass and function. Preservation of muscle mass depends in part on satellite cells, the resident stem cells of skeletal muscle. Reduced satellite cell function may contribute to the age-associated decrease in muscle mass. Recent studies have delineated that the aging process in organ stem cells is largely caused by age-specific changes in the differentiated niches, and that regenerative outcomes often depend on the age of the niche, rather than on stem cell age. It is likely that epigenetic states will be better define such key satellite cell features as prolonged quiescence and lineage fidelity. It is also likely that DNA and histone modifications will underlie many of the changes in aged satellite cells that account for age-related declines in functionality and rejuvenation through exposure to the systemic environment.SUMMARY: Skeletal muscle aging results in a gradual loss of skeletal muscle mass, skeletal muscle function and regenerative capacity, which can lead to sarcopenia and increased mortality. Although the mechanisms underlying sarcopenia remain unclear, the skeletal muscle stem cell, or satellite cell, is required for muscle regeneration. Decreased muscle stem cell function in aging has long been shown to depend on altered environmental cues, whereas the contribution of intrinsic mechanisms remained less clear. Signals in the aged niche were shown to cause permanent defects in the ability of satellite cells to return to quiescence, ultimately also impairing the maintenance of self-renewing satellite cells. Therefore, only anti-aging strategies taking both factors, the stem cell niche and the stem cells per se, into consideration may ultimately be successful.KEYWORDS: satellite cell, muscle, aging, niche, regenerations

scholarly journals Novel Intriguing Strategies Attenuating to Sarcopenia

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Kunihiro Sakuma ◽  
Akihiko Yamaguchi
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Ursolic Acid ◽  
Proteasome Inhibition ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Homeostasis ◽  
Age Related ◽  
Increased Risk ◽  
Risk Of Fall

Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA) or ursolic acid, etc.) for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptorγcoactivator 1α(PGC-1α) in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant.

scholarly journals Mitochondrial Impairment in Sarcopenia

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 31
Author(s):  
Francesco Bellanti ◽  
Aurelio Lo Buglio ◽  
Gianluigi Vendemiale
Keyword(s):  
Skeletal Muscle ◽  
Muscle Quality ◽  
Protein Homeostasis ◽  
Related Condition ◽  
Selective Autophagy ◽  
Mitochondrial Homeostasis ◽  
Mitochondrial Alterations ◽  
Mitochondrial Impairment ◽  
Age Related ◽  
And Function

Sarcopenia is defined by the age-related loss of skeletal muscle quality, which relies on mitochondrial homeostasis. During aging, several mitochondrial features such as bioenergetics, dynamics, biogenesis, and selective autophagy (mitophagy) are altered and impinge on protein homeostasis, resulting in loss of muscle mass and function. Thus, mitochondrial dysfunction contributes significantly to the complex pathogenesis of sarcopenia, and mitochondria are indicated as potential targets to prevent and treat this age-related condition. After a concise presentation of the age-related modifications in skeletal muscle quality and mitochondrial homeostasis, the present review summarizes the most relevant findings related to mitochondrial alterations in sarcopenia.

scholarly journals High Resolution Genome Wide Expression Analysis of Single Myofibers Using SMART-Seq

2019 ◽  
Author(s):  
Darren M. Blackburn ◽  
Felicia Lazure ◽  
Aldo H. Corchado ◽  
Theodore J. Perkins ◽  
Hamed S. Najafabadi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
High Resolution ◽  
Expression Analysis ◽  
Expression Profiles ◽  
Age Related ◽  
Genome Wide ◽  
Heterogeneous Tissue ◽  
Whole Transcriptome ◽  
Old Mice ◽  
Genome Wide Expression

ABSTRACTSkeletal muscle is a heterogeneous tissue. Individual myofibers that make up muscle tissue exhibit variation in their metabolic and contractile properties. Although there are biochemical and histological assays to study myofiber heterogeneity, efficient methods to analyze the whole transcriptome of individual myofibers are lacking. We have developed single myofiber RNA-Seq (smfRNA-Seq) to analyze the whole transcriptome of individual myofibers by combining single fiber isolation with Switching Mechanisms at 5’ end of RNA Template (SMART) technology. Our method provides high-resolution genome wide expression profiles of single myofibers. Using smfRNA-Seq, we have analyzed the differences in the transcriptome of young and old myofibers to validate the effectiveness of this new method. Using smfRNA-Seq, we performed comparative gene expression analysis between single myofibers from young and old mice. Our data suggests that aging leads to significant changes in the expression of metabolic and structural genes in myofibers. Our data suggests that smfRNA-Seq is a powerful tool to study developmental, disease and age-related dynamics in the composition of skeletal muscle.

scholarly journals Depletion of the miR-34a “sponge” MALAT1 in aging skeletal muscle: Implications for age-related muscle loss

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 689-689
Author(s):  
Ling Ruan ◽  
Mark Hamrick ◽  
Bharati Mendhe ◽  
Carlos Isales ◽  
William Hill ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Hydrogen Peroxide ◽  
C2c12 Cells ◽  
Therapeutic Interventions ◽  
Myoblast Differentiation ◽  
H2o2 Treatment ◽  
Muscle Aging ◽  
Age Related ◽  
Competing Endogenous Rnas ◽  
P53 Activation

Abstract We have recently shown that increased levels of reactive oxygen species (ROS) in aging skeletal muscle are associated with increased expression of the senescence-associated microRNA miR-34a-5p (miR-34a). The histone deacetylase Sirt1 is a validated target of miR-34a, and miR-34a expression is induced by the tumor suppressor p53 which is itself stimulated by ROS. Long noncoding RNAs (lncRNAs) are known to function as “sponges” for microRNAs, but the role of such competing endogenous RNAs (ceRNA) in muscle aging is not well understood. We therefore examined in skeletal muscles of young (4-6 mos) and aged (22-24) male and female mice the expression of several lncRNAs that are predicted to bind miR-34a-5p in silico and whose predicted binding has been validated experimentally. Results indicate a significant decrease in lncRNA MALAT1 expression with aging. MALAT1 is known to be highly expressed during the later stages of myoblast differentiation and myotube maturation. We therefore treated C2C12 cells at 48 hrs with hydrogen peroxide (10 uM) and examined changes in MALAT1 expression. MALAT1 was significantly decreased with H2O2 treatment, whereas miR-34a is increased in C2C12 cells after hydrogen peroxide exposure. Age-related muscle atrophy mediated by ROS may therefore result in part from related mechanisms involving miR-34a activity: an increase in miR-34a targeting Sirt1 resulting from p53 activation and an increase in miR-34a bioavailability resulting from a decline in miR-34a “sponging” due to ceRNA MALAT1 depletion. These findings suggest that therapeutic interventions increasing MALAT1 expression in muscle may potentially enhance the preservation of muscle mass with aging.

scholarly journals Exercise rescues mitochondrial coupling in aged skeletal muscle: a comparison of different modalities in preventing sarcopenia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Colin Harper ◽  
Venkatesh Gopalan ◽  
Jorming Goh
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Fiber Type ◽  
Skeletal Muscle Function ◽  
Atp Production ◽  
Muscle Aging ◽  
Age Related ◽  
Key Factor ◽  
Underlying Mechanisms ◽  
Skeletal Muscle Aging

AbstractSkeletal muscle aging is associated with a decline in motor function and loss of muscle mass- a condition known as sarcopenia. The underlying mechanisms that drive this pathology are associated with a failure in energy generation in skeletal muscle, either from age-related decline in mitochondrial function, or from disuse. To an extent, lifelong exercise is efficacious in preserving the energetic properties of skeletal muscle and thus may delay the onset of sarcopenia. This review discusses the cellular and molecular changes in skeletal muscle mitochondria during the aging process and how different exercise modalities work to reverse these changes. A key factor that will be described is the efficiency of mitochondrial coupling—ATP production relative to O2 uptake in myocytes and how that efficiency is a main driver for age-associated decline in skeletal muscle function. With that, we postulate the most effective exercise modality and protocol for reversing the molecular hallmarks of skeletal muscle aging and staving off sarcopenia. Two other concepts pertinent to mitochondrial efficiency in exercise-trained skeletal muscle will be integrated in this review, including- mitophagy, the removal of dysfunctional mitochondrial via autophagy, as well as the implications of muscle fiber type changes with sarcopenia on mitochondrial function.

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