Regulation of microRNAs in skeletal muscle adaptation in aging: Comparison
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Sarcopenia refers to a condition of progressive loss of skeletal muscle mass and function associated with a higher risk of falls and fractures in older adults. Musculoskeletal aging leads to reduced muscle mass and strength, affecting the quality of life in elderly people. In recent years, several studies contributed to improve the knowledge of the pathophysiological alterations that lead to skeletal muscle dysfunction; however, the molecular mechanisms underlying sarcopenia are still not fully understood. Muscle development and homeostasis require a fine gene expression modulation by mechanisms in which microRNAs (miRNAs) play a crucial role. miRNAs modulate key steps of skeletal myogenesis including satellite cells renewal, skeletal muscle plasticity, and regeneration.

  • miRNA
  • sarcopenia
  • skeletal muscle
  • exercise

1. Introduction

Sarcopenia is a pathophysiological process characterized by progressive loss of skeletal muscle mass and function that contributes to a higher risk of falls and fractures among older adults [1]. It often leads to frailty that impacts considerably on the quality of life in elderly people. After the age of 50, the rate of muscle loss is estimated to be 1–2% per year, being faster in men than women [2]. The advances in transcriptomics technologies and high throughput analyses allow for detection of a broad repertoire of cellular factors that participate to gene expression regulation during skeletal muscle aging changes and adaptations such as growth factors, transcription factors, cell signaling pathways activators, and non-coding RNA, including microRNAs (miRNAs) [3].miRNAs are a class of non-coding transcripts specifically involved in negatively modulated gene expression at the post-transcriptional levels by specifically targeting the 3′-untranslated regions (3′-UTR) of their target mRNAs. Several miRNAs have been demonstrated to participate in the molecular mechanisms that control skeletal muscle plasticity during aging. miRNAs that are preferentially expressed in striated muscle are termed as myomiRs, and they act as regulators of muscle development, homeostasis, and functionality [4][5]. Expression of skeletal myomiRs may be altered in old skeletal muscle, in age- and activity-related muscle changes (e.g., hypertrophy, atrophy), as well as in myopathies, such as muscular dystrophy [6][7][8][9]. Recent studies have demonstrated that muscle-specific miRNAs play a pivotal role in the control of sarcopenia, modulating key steps of skeletal myogenesis, including satellite cells senescence, cell proliferation, and differentiation [10][11].The reduction in force of skeletal muscle in older people is primarily due to the loss and weakening of muscle fibers. For instance, during aging, the locomotor skeletal muscles face a marked switch to slow type I myofibers, a process of atrophy of fast (type IIa and IIx) fibers, with a reduction in the myofiber count [12][13][14]. Similar changes have been associated with sedentary lifestyles, and reported in some neuromuscular disorders[6][15][16][17][18]. Thus, exercise is considered an effective intervention to delay the onset and progression of sarcopenia. Regular exercise training has been associated with an increase in skeletal muscle cross-sectional area, force, and resistance to fatigue [19], as well as improvements in cardiovascular fitness and quality of life [20]. Exercise training promotes positive adaptations in skeletal muscle, acting as an important stimulator of extra/intracellular signals, leading to changes in gene expression. Several studies have revealed that miRNA expression in skeletal muscle is modulated in response to physical exercise, see the exhaustive reviews [21][22][23], highlighting the relevance of the miRNAs role in the process of adaptation to exercise. More recently, circulating miRNAs have been investigated as possible biomarkers of exercise training [24].

2.  miRNA Biogenesis and Functional Role

miRNAs are small non-coding RNAs of 20 nucleotides in length, transcribed by about 2000 human genes, that regulate gene expression at the post-transcriptional level [25][26]. miRNAs play crucial roles in various biological processes such as cell proliferation, apoptosis, differentiation as well as epigenetic changes and metabolic homeostasis. miRNA genes are often found in clusters and may derive from intragenic or intergenic regions, both intronic and exonic [27]. miRNAs biogenesis begins with the synthesis of primary miRNAs (pri-miRNAs) by RNA polymerase II that are processed in the nucleus into precursor miRNAs of approximately 70 nt (pre-miRNAs) by a complex consisting of the RNA binding protein, DGCR8 microprocessor subunit, and the endoribonuclease, Drosha [28]. Pre-miRNAs are then exported to the cytoplasm via the nuclear transport protein Exportin 5, where the endoribonuclease Dicer cuts the stem loop region producing miRNAs duplexes. miRNAs duplexes harbor the mature miRNA strand that, once associated with the RNA induced silencing (RISC) complex, works as a gene modulator at the transcriptional level.miRNAs regulate transcripts expression generally by annealing to the 3′ untranslated region (3′UTR), leading to inhibition of mRNA translation and/or degradation of mRNA transcripts. miRNA may target mRNA not only at their 3′-UTR, but also at the 5′UTR, promoters and exon sequences, generally leading to downregulation of the expressed genes [29]. Each miRNA can target several mRNAs involved in different cell functions and in a crosstalk between cell signaling pathways. Deregulation of miRNA expression has been associated with several pathological processes, including cancer, neurodegenerative diseases, cardiovascular diseases, and host response to viral infections [30][31][32][33].

3.  Skeletal Myogenesis and Sarcopenia

Skeletal myogenesis refers to the process of muscle development, whereby myogenic precursor cells can differentiate and fuse to form myofibers. During development, most of the precursor cells undergo proliferation and differentiation, while a subset remains capable of regeneration, repairing tissue injuries in adulthood. Myogenesis involves an intricate regulatory network of gene expression that coordinates (i) activation and proliferation of stem cells that differentiate into myoblasts, (ii) early differentiation that consists in the fusion of myoblasts to form myocytes and (iii) terminal differentiation into myofibers (Figure 1). The skeletal myogenic process is finely regulated by transcription factors known as myogenic regulatory factors (MRFs), such as MyoD (myogenic differentiation), myogenin, Myf5 (myogenic factor 5), and MRF4 (myogenic regulatory factor 4) [34]. In adults, muscle stem cells, termed satellite cells, are characterized by the expression of the paired box transcription factor Pax7 and to a small extent of Pax3, whereas MyoD is not expressed. This pattern of expression allows the maintenance of satellite cells in a quiescent status. Activation of satellite cells from the quiescent status is first determined by a co-expression of Pax7, MyoD, and Myf5 [17]. At this step, Pax factors promote the expression of genes accountable for inducing a transient cell proliferation suppressing genes that induce differentiation. During myogenic differentiation, the expression of Pax proteins is suppressed, allowing the expression of MRFs. At this step, myogenin plays a key role in the terminal differentiation of myogenic progenitor cells, whereas MyoD undergoes to downregulation. In the aging muscle, the expression of the myogenic genes, MyoD, and myogenin, have been reported to be upregulated, suggesting a modification of the committed status of the muscle satellite cells [35].

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Figure 1. MicroRNAs (miRNAs) and target genes implicated in skeletal muscle myogenesis.

4.  The Role of miRNAs during Skeletal Myogenesis in Adults

MRFs expression can be regulated by miRNAs highlighting their involvement in modulating myogenesis. A set of miRNAs, referred to as myomiRs, such as miR-1, miR-133a, miR-133b, miR-206, miR-208, miR-208b, miR-486, and miR-499, are highly enriched in muscle fibers [18]. MyomiRs may modulate size and type transition of muscle fibers in structural adaptation to aging and exercise. Specifically, miR-499, miR-208 and miR-208b, encoded by intron sequences of myosin heavy chain genes, have been demonstrated in mice models to participate in a network of miRNAs that regulate not only myosin expression, but also fiber type genes expression and muscle performance [36]. Skeletal muscle-specific Dicer knockout in mice results in low expression of specific miRNAs, reduced skeletal muscle mass, and abnormal myofibers morphology, confirming that a correct maturation of miRNAs is necessary for muscle development and function [37]. In adult mice, depletion of Dicer has been demonstrated to reduce the expression of miR-1, miR-133a and miR-206 expression; however, this reduction had no effect on skeletal muscle mass and phenotype, even after a long-life reduction [38]. In contrast, the reduction of myomiRs after Dicer knockout affects skeletal muscle regeneration [39]. Unexpected results derived by Dicer depletion studies in adult mice skeletal muscle showed that, even if Dicer expression might be reduced of almost 80%, myomiRs expression was not as much significantly reduced. This finding opens interest for further studies that may investigate the effectiveness of Dicer function and myomiRs stability and function in adult muscle. Several reviews have extensively described the role of miRNAs during embryonal skeletal myogenesis [22][23][40]. Here we report and discuss the most recent evidence concerning miRNA regulatory network in adults. A selected list of myomiRs and miRNAs implicated in the different phases of skeletal myogenesis from quiescence to the proliferation of satellite cells and myofibers differentiation are represented in Figure 1.

5.  Role of miRNAs in Skeletal Muscle Aging and Sarcopenia

Several studies have demonstrated that miRNAs are implicated in the alteration of skeletal muscle homeostasis and function during aging. Comparative studies in young and old muscle tissues of rodents, monkeys and humans showed differential expression of several miRNAs involved in the control of the myogenic processes [41][42][43]. The differentially expressed miRNA during aging, target factors that regulate cell cycle progression, the insulin-like growth factors (IGFs), factors involved in the process of cell senescence such as SIRT1 and telomerase reverse transcriptase (TERT), and factors of the transforming growth factor-β (TGF-β) cell signaling pathways (Figure 2).

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Figure 2. miRNAs involved in the regulation of age-related pathways in skeletal muscle.

6.  miRNAs Are Regulated by Exercise in Sarcopenia

Skeletal muscle exhibits an extraordinary plasticity dictated by a fine balance between anabolic and catabolic processes [16]. Muscle composition is influenced by internal and external stimuli (e.g., the intrinsic cellular aging process or environmental factors) that can accelerate or temporize the functional muscle impairment associated with aging and the sedentary behavior [5][6][44]. Indeed, aging is associated with a decrease in muscle protein synthesis [45], mitochondrial dysfunction, as well as a loss of fast glycolytic fibers and reduced blood perfusion [46][47][48]. Therefore, older people show a characteristic weakening, deterioration, and muscle loss, accompanied by microvascular impaired perfusion and an underlying state of inflammation [49][50]. This turnover is detrimental for healthy aging but is partially reversible with physical activity [51][52]. To date, lifestyle interventions and exercise training represent the primary, most effective, and non-pharmacological approach to prevent and treat sarcopenia-related decline. Exercise is prescribed with different approaches, including customized type, frequency, intensity, and duration, to endorse positive outcomes. The most common and studied models of exercise can be distinguished in endurance and resistance: the latter is characterized by low intensity, long-duration aerobic activity, the former by higher intensities, short bouts with primary involvement of the anaerobic pathways. Endurance training is mainly known for its positive effects on the cardiovascular fitness (i.e., maximal oxygen consumption), but it also induces mitochondrial biogenesis, increases oxidative enzyme activity with a reduction in ROS generation, promotes muscle vascularization and regulates vascular tone [53][54]. The changes in muscle metabolism enhance the all-body aerobic fitness capacity (peak VO2 uptake) and attenuate the age-associated decline in the peripheral and central vasculature and cardiac functions [55][56]. Considering that the main feature of aging and sarcopenia is muscle atrophy, resistance exercise training is the most indicated, as it elicits the biosynthesis of contractile and structural proteins, resulting in muscle hypertrophy [57]. Specifically, resistance training significantly increases the number and cross-sectional area of type II fibers [53][54]. This improvement in muscle fibers results in a general improvement in functional capacity, muscular endurance, and quality of life [10]. miRNA expression may be adapted in response to exercise and altered miRNA profile may contribute to affect the plasticity of aged muscle [58][59]. Understanding the signaling pathways regulated by these miRNAs allows to shed light on the molecular mechanisms associated to improved muscle anatomy and function and may help establish specific protocols of training.

7.  Conclusions

Sarcopenia-related muscle dysfunction significantly affects life quality of elderly people. Skeletal muscle development, homeostasis, and metabolism during aging undergo changes in terms of gene expression regulation in which miRNAs have been demonstrated to play a crucial role. With aging, the altered expression profile of miRNAs that regulate the central processes of muscle cell biology contributes to the loss of muscle mass. Further studies on the molecular mechanisms of regulation of miRNAs during the multiple steps of skeletal myogenesis, as well as in sarcopenic/atrophy conditions will shed light to our knowledge on the functionality of skeletal muscle and on the identification of potential targets for therapies.

References

  1. Wilkinson, D.J.; Piasecki, M.; Atherton, P.J. The Age-Related Loss of Skeletal Muscle Mass and Function: Measurement and Physiology of Muscle Fibre Atrophy and Muscle Fibre Loss in Humans. Ageing Res. Rev. 2018, 47, 123–132, doi:10.1016/j.arr.2018.07.005.
  2. Sannicandro, A.J.; Soriano-Arroquia, A.; Goljanek-Whysall, K. Micro(RNA)-Managing Muscle Wasting. J. Appl. Physiol. 2019, 127, 619–632, doi:10.1152/japplphysiol.00961.2018.
  3. Schmidt, M.; Schüler, S.C.; Hüttner, S.S.; von Eyss, B.; von Maltzahn, J. Adult Stem Cells at Work: Regenerating Skeletal Muscle. Cell Mol. Life Sci. 2019, 76, 2559–2570, doi:10.1007/s00018-019-03093-6.
  4. Horak, M.; Novak, J.; Bienertova-Vasku, J. Muscle-Specific MicroRNAs in Skeletal Muscle Development. Dev. Biol. 2016, 410, 1–13, doi:10.1016/j.ydbio.2015.12.013.
  5. Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297, doi:10.1016/s0092-867400045-5.
  6. Güller, I.; Russell, A.P. MicroRNAs in Skeletal Muscle: Their Role and Regulation in Development, Disease and Function. J. Physiol. 2010, 588, 4075–4087, doi:10.1113/jphysiol.2010.194175.
  7. Moresi, V.; Marroncelli, N.; Coletti, D.; Adamo, S. Regulation of Skeletal Muscle Development and Homeostasis by Gene Imprinting, Histone Acetylation and MicroRNA. Biochim. Biophys. Acta 2015, 1849, 309–316, doi:10.1016/j.bbagrm.2015.01.002.
  8. Nie, M.; Deng, Z.-L.; Liu, J.; Wang, D.-Z. Noncoding RNAs, Emerging Regulators of Skeletal Muscle Development and Diseases. Biomed Res. Int. 2015, 2015, 676575, doi:10.1155/2015/676575.
  9. Zhao, Y.; Chen, M.; Lian, D.; Li, Yan.; Li, Yao.; Wang, J.; Deng, S.; Yu, K.; Lian, Z. Non-Coding RNA Regulates the Myogenesis of Skeletal Muscle Satellite Cells, Injury Repair and Diseases. Cells 2019, 8, 988, doi:10.3390/cells8090988.
  10. Jung, H.J.; Lee, K.-P.; Milholland, B.; Shin, Y.J.; Kang, J.S.; Kwon, K.-S.; Suh, Y. Comprehensive MiRNA Profiling of Skeletal Muscle and Serum in Induced and Normal Mouse Muscle Atrophy During Aging. J. Gerontol A Biol. Sci. Med. Sci. 2017, 72, 1483–1491.doi:10.1093/gerona/glx025.
  11. Zheng, Y.; Kong, J.; Li, Q.; Wang, Y.; Li, J. Role of MiRNAs in Skeletal Muscle Aging. Clin. Interv. Aging 2018, 13, 2407–2419, doi:10.2147/CIA.S169202.
  12. Kosek, D.J.; Kim, J.S.; Petrella, J.K.; Cross, J.M.; Bamman, M.M. Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. J. Appl. Physiol. 2006, 101, 531–544, doi:10.1152/japplphysiol.01474.2005.
  13. Nilwik, R.; Snijders, T.; Leenders, M.; Groen, B.B.; van Kranenburg, J.; Verdijk, L.B.; van Loon, L.J. The decline in skeletal muscle mass with aging is mainly attributed to a reduction in type II muscle fiber size. Exp. Gerontol. 2013, 48, 492–498, doi:10.1016/j.exger.2013.02.012.
  14. Lexell, J.; Downham, D.; Sjöström, M. Distribution of different fibre types in human skeletal muscles. Fibre type arrangement in m. vastuslateralis from three groups of healthy men between 15 and 83 years. J. Neurol. Sci. 1986, 72, 211–222, doi:10.1016/0022-510X(86)90009-2.
  15. Cavedon, V.; Milanese, C.; Laginestra, F.G.; Giuriato, G.; Pedrinolla, A.; Ruzzante, F.; Schena, F.; Venturelli, M. Bone and skeletalmusclechanges in oldest-oldwomen: The role of physicalinactivity. Aging Clin. Exp. Res. 2020, 32, 207–214, doi:10.1007/s40520-019-01352-x.
  16. Naro, F.; Venturelli, M.; Monaco, L.; Toniolo, L.; Muti, E.; Milanese, C.; Zhao, J.; Richardson, R.S.; Schena, F.; Reggiani, C. Skeletal Muscle Fiber Size and Gene Expression in the Oldest-Old With Differing Degrees of Mobility. Front. Physiol. 2019, 10, 313, doi:10.3389/fphys.2019.00313.
  17. Venturelli, M.; Saggin, P.; Muti, E.; Naro, F.; Cancellara, L.; Toniolo, L.; Tarperi, C.; Calabria, E.; Richardson, R.S.; Reggiani, C.; et al. In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse in oldest-old humans. Acta Physiol. 2015, 215, 58–71, doi:10.1111/apha.12524.
  18. Venturelli, M.; Reggiani, C.; Richardson, R.S.; Schena, F. Skeletal Muscle Function in the Oldest-Old: The Role of Intrinsic and Extrinsic Factors. Exerc. Sport Sci. Rev. 2018, 46, 188–194, doi:10.1249/JES.0000000000000155.
  19. Bogdanis, G.C. Effects of Physical Activity and Inactivity on Muscle Fatigue. Front. Physiol. 2012, 3, 142, doi:10.3389/fphys.2012.00142.
  20. Borst, S.E. Interventions for sarcopenia and muscle weakness in older people. Age Ageing 2004, 33, 548–555, doi:10.1093/ageing/afh201.
  21. Zacharewicz, E.; Lamon, S.; Russell, A.P. MicroRNAs in Skeletal Muscle and Their Regulation with Exercise, Ageing, and Disease. Front. Physiol. 2013, 4, 266, doi:10.3389/fphys.2013.00266.
  22. Domańska-Senderowska, D.; Laguette, M.-J. N.; Jegier, A.; Cięszczyk, P.; September, A.V.; Brzeziańska-Lasota, E. MicroRNA Profile and Adaptive Response to Exercise Training: A Review. Int. J. Sports Med. 2019, 40, 227–235, doi:10.1055/a-0824-4813.
  23. Da Silva, F.C.; da Rosa Iop, R.; Andrade, A.; Costa, V.P.; Filho, P.J.B.G.; da Silva, R. Effects of Physical Exercise on the Expression of MicroRNAs: A Systematic Review. J. Strength. Cond. Res. 2020, 34, 270–280, doi:10.1519/JSC.0000000000003103.
  24. Zhou, Q.; Shi, C.; Lv, Y.; Zhao, C.; Jiao, Z.; Wang, T. Circulating MicroRNAs in Response to Exercise Training in Healthy Adults. Front. Genet. 2020, 11, 256, doi:10.3389/fgene.2020.00256.
  25. Alles, J.; Fehlmann, T.; Fischer, U.; Backes, C.; Galata, V.; Minet, M.; Hart, M.; Abu-Halima, M.; Grässer, F.A.; Lenhof, H.P.; et al. An estimate of the total number of true human miRNAs. Nucleic. Acids Res. 2019, 47, 3353–3364, doi:10.1093/nar/gkz097.
  26. O'Brien, J.; Hayder, H.; Zayed, Y.; Peng, C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front. Endocrinol. (Lausanne) 2018, 9, 402, doi:10.3389/fendo.2018.00402.
  27. Rodriguez, A.; Griffiths-Jones, S.; Ashurst, J.L.; Bradley, A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004, 14, 1902–1910, doi:10.1101/gr.2722704.
  28. Ha, M.; Kim, V.N. Regulation of microRNA biogenesis. Nat. Rev. Mol. Cell Biol. 2014, 15, 509–524, doi:10.1038/nrm3838.
  29. Broughton, J.P.; Lovci, M.T.; Huang, J.L.; Yeo, G.W.; Pasquinelli, A.E. Pairing beyond the Seed Supports MicroRNA Targeting Specificity. Cell 2016, 64, 320–333, doi:10.1016/j.molcel.2016.09.004.
  30. Slack, F.J.; Chinnaiyan, A.M. The Role of Non-coding RNAs in Oncology. Cell 2019, 179, 1033–1055, doi:10.1016/j.cell.2019.10.017.
  31. Juźwik, C.A.; Drake, S.; Zhang, Y.; Paradis-Isler, N.; Sylvester, A.; Amar-Zifkin, A.; Douglas, C.; Morquette, B.; Moore, C.S.; Fournier, A.E. microRNA dysregulation in neurodegenerative diseases: A systematic review. Prog. Neurobiol. 2019, 182, 101664, doi:10.1016/j.pneurobio.2019.101664.
  32. Fochi, S.; Ciminale, V.; Trabetti, E.; Bertazzoni, U.; D’Agostino, D.M.; Zipeto, D.; Romanelli, M.G. NF-κB and MicroRNA Deregulation Mediated by HTLV-1 Tax and HBZ. Pathogens 2019, 8, 290, doi:10.3390/pathogens8040290.
  33. Calderon-Dominguez, M.; Belmonte, T.; Quezada-Feijoo, M.; Ramos-Sánchez, M.; Fernández-Armenta, J.; Pérez-Navarro, A.; Cesar, S.; Peña-Peña, L.; Vea, À.; Llorente-Cortés, V.; Mangas, A.; et al. Emerging role of microRNAs in dilated cardiomyopathy: Evidence regarding etiology. Transl. Res. 2020, 215, 86–101, doi:10.1016/j.trsl.2019.08.007.
  34. Asfour, H.A.; Mohammed, Z.A.; Raed, S.S. Myogenic Regulatory Factors: The Orchestrators of Myogenesis after 30 Years of Discovery. Exp. Biol. Med. (Maywood) 2018, 243, 118–128, doi:10.1177/1535370217749494.
  35. Musarò, A.; Cusella De Angelis, M.G.; Germani, A.; Ciccarelli, C.; Molinaro, M.; Zani, B.M. Enhanced expression of myogenic regulatory genes in aging skeletal muscle. Exp. Cell Res. 1995, 221, 241–248, doi:10.1006/excr.1995.1372.
  36. Van Rooij, E.; Quiat, D.; Johnson, B.A.; Sutherland, L.B.; Qi, X.; Richardson, J.A.; Kelm, R.J.; Olson, E.N.; Jr. A family of microRNAs encoded by myosin genes governs myosin expression and muscle performance. Dev. Cell 2009, 17, 662–673, doi:10.1016/j.devcel.2009.10.013.
  37. O'Rourke, J.R.; Georges, S.A.; Seay, H.R.; Tapscott, S.J.; McManus, M.T.; Goldhamer, D.J.; Swanson, M.S.; Harfe, B.D. Essential Role for Dicer during Skeletal Muscle Development. Dev. Biol. 2007, 311, 359–368, doi:10.1016/j.ydbio.2007.08.032.
  38. Vechetti, I.J.; Wen, Y., Jr.; Chaillou, T.; Murach, K.A.; Alimov, A.P.; Figueiredo, V.C.; Dal-Pai-Silva, M.; McCarthy, J.J. Life-long reduction in myomiR expression does not adversely affect skeletal muscle morphology. Sci. Rep. 2019, 9, 5483, doi:10.1038/s41598-019-41476-8.
  39. Oikawa, S.; Lee, M.; Akimoto, T. Conditional Deletion of Dicer in Adult Mice Impairs Skeletal Muscle Regeneration. Int. J. Mol. Sci. 2019, 20, 5686, doi:10.3390/ijms20225686.
  40. Kirby, T.J.; Chaillou, T.; McCarthy, J.J. The Role of MicroRNAs in Skeletal Muscle Health and Disease. Front. Biosci. 2015, 20, 37–77, doi:10.2741/4298.
  41. Drummond, M.J.; McCarthy, J.J.; Fry, C.S.; Esser, K.A.; Rasmussen, B.B. Aging Differentially Affects Human Skeletal Muscle MicroRNA Expression at Rest and after an Anabolic Stimulus of Resistance Exercise and Essential Amino Acids. Am. J. Physiol. Endocrinol. Metab. 2008, 295, E1333–E1340, doi:10.1152/ajpendo.90562.2008.
  42. Hamrick, M.W.; Herberg, S.; Arounleut, P.; He, H.Z.; Shiver, A.; Qi, R.Q.; Zhou, L.; Isales, C.M.; Mi, Q.S. The Adipokine Leptin Increases Skeletal Muscle Mass and Significantly Alters Skeletal Muscle MiRNA Expression Profile in Aged Mice. Biochem. Biophys. Res. Commun. 2010, 400, 379–383, doi:10.1016/j.bbrc.2010.08.079.
  43. Mercken, E.M.; Majounie, E.; Ding, J.; Guo, R.; Kim, J.; Bernier, M.; Mattison, J.; Cookson, M.R.; Gorospe, M.; de Cabo, R.; et al. Age-Associated MiRNA Alterations in Skeletal Muscle from Rhesus Monkeys Reversed by Caloric Restriction. Aging 2013, 5, 692–703, doi:10.18632/aging.100598.
  44. Venturelli, M.; Morgan, G.R.; Donato, A.J.; Reese, V.; Bottura, R.; Tarperi, C.; Milanese, C.; Schena, F.; Reggiani, C.; Naro, F.; et al. Cellular aging of skeletal muscle: Telomeric and free radical evidence that physical inactivity is responsible and not age. Clin. Sci. 2014, 127, 415–421, doi:10.1042/CS20140051.
  45. Kumar, V.; Selby, A.; Rankin, D.; Patel, R.; Atherton, P.; Hildebrandt, W.; Williams, J.; Smith, K.; Seynnes, O.; Hiscock, N.; et al. Age-Related Differences in the Dose-Response Relationship of Muscle Protein Synthesis to Resistance Exercise in Young and Old Men. J. Physiol. 2009, 587, 211–217, doi:10.1113/jphysiol.2008.164483.
  46. Iannuzzi-Sucich, M.; Prestwood, K.M.; Kenny, A.M. Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women . J. Gerontol A Biol. Sci. Med. Sci. 2002, 57, M772–M777, doi:10.1093/gerona/57.12.M772.
  47. Marzetti, E.; Calvani, R.; Cesari, M.; Buford, T.W.; Lorenzi, M.; Behnke, B.J.; Leeuwenburgh, C. Mitochondrial dysfunction and sarcopenia of aging: From signaling pathways to clinical trials. Int. J. Biochem. Cell Biol. 2013, 45, 2288–2301, doi:10.1016/j.biocel.2013.06.024.
  48. Prior, S.J.; Ryan, A.S.; Blumenthal, J.B.; Watson, J.M.; Katzel, L.I.; Goldberg, A.P. Sarcopenia Is Associated With Lower Skeletal Muscle Capillarization and Exercise Capacity in Older Adults. J. Gerontol A Biol. Sci. Med. Sci. 2016, 71, 1096–1101, doi:10.1093/gerona/glw017.
  49. Merritt, E.K.; Stec, M.J.; Thalacker-Mercer, A.; Windham, S.T.; Cross, J.M.; Shelley, D.P.; Craig Tuggle, S.; Kosek, D.J.; Kim, J.S.; Bamman, M.M. Heightened muscle inflammation susceptibility may impair regenerative capacity in aging humans. J. Appl. Physiol. 2013, 115, 937–948, doi:10.1152/japplphysiol.00019.2013.
  50. Beyer, I. , Mets, T.; Ivan Bautmans, I. Chronic low-grade inflammation and age-related sarcopenia. Curr. Opin. Clin. Nutr. Metab. Care 2012, 5, 12–22, doi:10.1097/MCO.0b013e32834dd297.
  51. Layec, G.; Trinity, J.D.; Hart, C.R.; Le Fur, Y.; Zhao, J.; Reese, V.; Jeong, E.K.; Richardson, R.S. Impaired Muscle Efficiency but Preserved Peripheral Hemodynamics and Mitochondrial Function With Advancing Age: Evidence From Exercise in the Young, Old, and Oldest-Old. J. Gerontol A Biol. Sci. Med. Sci. 2018, 73, 1303–1312, doi:10.1093/gerona/gly050.
  52. Gopinath, B.; Kifley, A.; Flood, V.M.; Mitchell, P. Physical Activity as a Determinant of Successful Aging over Ten Years. Sci. Rep. 2018, 8, 10522, doi:10.1038/s41598-018-28526-3.
  53. Bickel, C.S.; Cross, J.M.; Bamman, M.M. Exercise dosing to retain resistance training adaptations in young and older adults. Med. Sci. Sports Exerc. 2011, 43, 1177–1187, doi:10.1249/MSS.0b013e318207c15d.
  54. Stec, M.J.; Thalacker-Mercer, A.; Mayhew, D.L.; Kelly, N.A.; Tuggle, S.C.; Merritt, E.K.; Brown, C.J.; Windham, S.T.; Dell’Italia, L.J.; Bickel, C.S.; et al. Randomized, four-arm, dose-response clinical trial to optimize resistance exercise training for older adults with age-related muscle atrophy. Exp. Gerontol. 2017, 99, 98–109, doi:10.1016/j.exger.2017.09.018.
  55. Groennebaek, T.; Vissing, K. Impact of Resistance Training on Skeletal Muscle Mitochondrial Biogenesis, Content, and Function. Front. Physiol. 2017, 8, 713, doi:10.3389/fphys.2017.00713.
  56. Adelnia, F.; Cameron, D.; Bergeron, C.M.; Fishbein, K.W.; Spencer, R.G.; Reiter, D.A.; Ferrucci, L. The Role of Muscle Perfusion in the Age-Associated Decline of Mitochondrial Function in Healthy Individuals. Front. Physiol. 2019, 10, 427, doi:10.3389/fphys.2019.00427.
  57. Petriz, B.A.; Gomes, C.P.; Almeida, J.A.; de Oliveira, G.P.; Ribeiro, F.M., Jr.; Pereira, R.W.; Franco, O.L. The Effects of Acute and Chronic Exercise on Skeletal Muscle Proteome. J. Cell Physiol. 2017, 232, 257–269, doi:10.1002/jcp.25477.
  58. Danese, E.; Benati, M.; Sanchis-Gomar, F.; Tarperi, C.; Salvagno, G.L.; Paviati, E.; Montagnana, M.; Schena, F.; Lippi, G. Influence of Middle-Distance Running on Muscular Micro RNAs. Scand. J. Clin. Lab. Investig. 2018, 78, 165–170, doi:10.1080/00365513.2018.1426104.
  59. Ultimo, S.; Zauli, G.; Martelli, A.M.; Vitale, M.; McCubrey, J.A.; Capitani, S.; Neri, L.M. Influence of Physical Exercise on MicroRNAs in Skeletal Muscle Regeneration, Aging and Diseases. Oncotarget 2018, 9, 17220–17237, doi:10.18632/oncotarget.24991.
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