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.

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 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 Basis for the Therapeutic Effects of Exercise on Mitochondrial Defects

2021 ◽  
Vol 11 ◽  
Author(s):  
Jonathan M. Memme ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dysfunction ◽  
Muscle Pathology ◽  
Therapeutic Effects ◽  
Atp Production ◽  
Muscle Aging ◽  
Mitochondrial Defects ◽  
Aging Muscle ◽  
Skeletal Muscle Aging ◽  
And Function

Mitochondrial dysfunction is common to many organ system disorders, including skeletal muscle. Aging muscle and diseases of muscle are often accompanied by defective mitochondrial ATP production. This manuscript will focus on the pre-clinical evidence supporting the use of regular exercise to improve defective mitochondrial metabolism and function in skeletal muscle, through the stimulation of mitochondrial turnover. Examples from aging muscle, muscle-specific mutations and cancer cachexia will be discussed. We will also examine the effects of exercise on the important mitochondrial regulators PGC-1α, and Parkin, and summarize the effects of exercise to reverse mitochondrial dysfunction (e.g., ROS production, apoptotic susceptibility, cardiolipin synthesis) in muscle pathology. This paper will illustrate the breadth and benefits of exercise to serve as “mitochondrial medicine” with age and disease.

scholarly journals Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius Furzeri Skeletal Muscle

2019 ◽  
Author(s):  
Chiara Cencioni ◽  
Johanna Heid ◽  
Anna Keprelova ◽  
Seyed Mohammad Mahdi Rasa ◽  
Carsten Kuenne ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Function ◽  
Muscle Aging ◽  
Aging Studies ◽  
Nothobranchius Furzeri ◽  
Landscape Alteration ◽  
Epigenetic Analysis ◽  
Skeletal Muscle Aging ◽  
Polycomb Complex

Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.

scholarly journals Maintenance of type 2 glycolytic myofibers with age by Mib1-Actn3 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Yun Seo ◽  
Jong-Seol Kang ◽  
Ye Lynne Kim ◽  
Young-Woo Jo ◽  
Ji-Hoon Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Function ◽  
Therapeutic Potential ◽  
Chronic Exercise ◽  
Skeletal Muscle Function ◽  
Age Related ◽  
Underlying Mechanisms ◽  
Exercise Induced

AbstractAge-associated muscle atrophy is a debilitating condition associated with loss of muscle mass and function with age that contributes to limitation of mobility and locomotion. However, the underlying mechanisms of how intrinsic muscle changes with age are largely unknown. Here we report that, with age, Mind bomb-1 (Mib1) plays important role in skeletal muscle maintenance via proteasomal degradation-dependent regulation of α-actinin 3 (Actn3). The disruption of Mib1 in myofibers (Mib1ΔMF) results in alteration of type 2 glycolytic myofibers, muscle atrophy, impaired muscle function, and Actn3 accumulation. After chronic exercise, Mib1ΔMF mice show muscle atrophy even at young age. However, when Actn3 level is downregulated, chronic exercise-induced muscle atrophy is ameliorated. Importantly, the Mib1 and Actn3 levels show clinical relevance in human skeletal muscles accompanied by decrease in skeletal muscle function with age. Together, these findings reveal the significance of the Mib1-Actn3 axis in skeletal muscle maintenance with age and suggest the therapeutic potential for the treatment or amelioration of age-related muscle atrophy.

Skeletal muscle aging

2007 ◽  
Vol 17 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Graeme L Close ◽  
Philippa Haggan ◽  
Anne McArdle
Keyword(s):  
Skeletal Muscle ◽  
Life Expectancy ◽  
Muscle Function ◽  
Active Life Expectancy ◽  
Active Life ◽  
Muscle Aging ◽  
Age Related ◽  
Dramatic Rise ◽  
Skeletal Muscle Aging

Average world life expectancy has seen a dramatic rise over the last two centuries although active life expectancy remains relatively unchanged. One reason for this is that aging results in skeletal muscle becoming smaller, weaker and more susceptible to contraction-induced injury. By the age of 70, muscle strength is reduced by around 30–40% and this can have catastrophic effects on quality of life. Despite a vast amount of research into age-related changes in skeletal muscle, the exact mechanisms responsible for this is still unclear and thus treatments to preserve muscle function with aging remain elusive.

scholarly journals Lifelong Ulk1-mediated autophagy deficiency in muscle induces mitochondrial dysfunction and contractile weakness

2020 ◽  
Author(s):  
Anna S. Nichenko ◽  
Jacob R. Sorensen ◽  
W. Michael Southern ◽  
Anita E. Qualls ◽  
Albino G. Schifino ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Tibialis Anterior Muscle ◽  
Metabolic Function ◽  
Metabolic Dysfunction ◽  
Cross Sectional ◽  
Mouse Muscle ◽  
Muscle Aging ◽  
Age Related ◽  
Skeletal Muscle Aging

AbstractThe accumulation of damaged mitochondria due to insufficient autophagy has been implicated in the pathophysiology of sarcopenia resulting in reduced contractile and metabolic function. Ulk1 is an autophagy-related kinase that initiates autophagosome assembly and may also play a role in autophagosome degradation (i.e., autophagy flux), but the contribution of Ulk1 to healthy muscle aging is unclear. We found that Ulk1 phosphorylation declines in both human and mouse muscle tissue with age, therefore the purpose of this study was to investigate the role of Ulk1-mediated autophagy in skeletal muscle aging. At age 22 months (80% survival rate), muscle contractile and metabolic function were assessed using electrophysiology in muscle specific Ulk1 knockout mice (MKO) and their littermate controls (LM). Specific peak-isometric torque of the ankle dorsiflexors (normalized by tibialis anterior muscle cross-sectional area) and specific force of the fast-twitch extensor digitorum longus muscles were reduced in MKO mice compared to LM mice (p<0.03). Permeabilized muscle fibers from MKO mice had greater mitochondrial content, yet lower mitochondrial oxygen consumption and greater reactive oxygen species production compared to fibers from LM mice (p≤ 0.04). Altered neuromuscular junction innervation patterns and changes in autophagosome numbers and/or flux in muscles from MKO may have contributed to decrements in contractile and metabolic function. Results from this study support an important role of Ulk1-mediated autophagy in skeletal muscle with age, reflecting Ulk1’s dual role in maintaining mitochondrial integrity through autophagosome assembly and degradation. A lifetime of insufficient Ulk-1-mediated autophagy in skeletal muscle exacerbates age-related contractile and metabolic dysfunction.

Resistance training, sarcopenia, and the mitochondrial theory of aging

2008 ◽  
Vol 33 (1) ◽  
pp. 191-199 ◽  
Author(s):  
Adam P.W. Johnston ◽  
Michael De Lisio ◽  
Gianni Parise
Keyword(s):  
Skeletal Muscle ◽  
Resistance Training ◽  
Resistance Exercise ◽  
Strength Function ◽  
Significant Loss ◽  
Muscle Aging ◽  
Age Related ◽  
Dna Deletions ◽  
Theory Of Aging ◽  
Skeletal Muscle Aging

Skeletal muscle aging is associated with a significant loss of muscle mass, strength, function, and quality of life. In addition, the healthcare cost of aging and age-related disease is growing, and will continue to grow as a larger proportion of our population reaches retirement age and beyond. The mitochondrial theory of aging has been identified as a leading explanation of the aging process and describes a path leading to cellular senescence that includes electron transport chain deficiency, reactive oxygen species production, and the accumulation of mitochondrial DNA deletions and mutations. It is also quite clear that regular resistance exercise is a potent and effective countermeasure for skeletal muscle aging. In this review, we discuss age-related sarcopenia, the mitochondrial theory of aging, and how resistance exercise may directly affect key components of the mitochondrial theory. It is clear from the data discussed that regular resistance training can effectively disturb processes that contribute to the progression of aging as it pertains to the mitochondrial theory.

scholarly journals Age-Related DNA Methylation Changes: Potential Impact on Skeletal Muscle Aging in Humans

2019 ◽  
Vol 10 ◽  
Author(s):  
Noémie Gensous ◽  
Maria Giulia Bacalini ◽  
Claudio Franceschi ◽  
Carel G. M. Meskers ◽  
Andrea B. Maier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Muscle Aging ◽  
Age Related ◽  
Potential Impact ◽  
Skeletal Muscle Aging

scholarly journals Aging Triggers H3K27 Trimethylation Hoarding in the Chromatin of Nothobranchius furzeri Skeletal Muscle

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1169 ◽  
Author(s):  
Chiara Cencioni ◽  
Johanna Heid ◽  
Anna Krepelova ◽  
Seyed Mohammad Mahdi Rasa ◽  
Carsten Kuenne ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Function ◽  
Muscle Aging ◽  
Aging Studies ◽  
Nothobranchius Furzeri ◽  
Landscape Alteration ◽  
Epigenetic Analysis ◽  
Skeletal Muscle Aging ◽  
Reduced Mobility

Aging associates with progressive loss of skeletal muscle function, sometimes leading to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated alteration in skeletal muscle. This study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as a consequence of increased levels of H3K27me3, HP1α, polycomb complex subunits, and senescence-associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, were significantly reduced. In this context, integrated bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation, and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms; however, our approach enlightened unprecedented features of Nfu skeletal muscle aging, potentially associated with swimming impairment and reduced mobility typical of old Nfu.

Sign in / Sign up

Export Citation Format

Share Document