Dataset Information

MicroRNAs in Skeletal Muscle Aging: Current Issues and Perspectives.

ABSTRACT: Skeletal muscle is one of the major organs responsible for body movements and metabolism making up approximately 40% of the total body mass. During aging, skeletal muscle exhibits a degenerative age-associated decline in mass and function termed sarcopenia. This age-associated dysfunction of skeletal muscle is a major criterion of morbidity, mortality, and overall declines of quality of life in the elderly people. Therefore, researchers have focused on identifying modulators of muscle aging process including messenger RNAs, proteins, and recently small noncoding RNAs such as microRNAs (miRNAs). In particular, miRNAs have been demonstrated to play a critical role in skeletal muscle development and homeostasis. Recent studies revealed that miRNAs were also involved in muscle aging processes and the rejuvenation of aged muscle by regulating important molecules and pathways of aging including insulin-like growth factors, nicotine-adenine dinucleotide (+)-dependent protein deacetylase sirtuin-1, telomerase reverse transcriptase, and transforming growth factor-? signaling pathway. Over the years, miRNAs have emerged as promising candidates for biomarkers of sarcopenia and targets for interventions to slow muscle aging. Here, we comprehensively review the current knowledge on the role of miRNAs in skeletal muscle aging and highlight their potential as biomarkers or therapeutic targets for skeletal muscle health.

SUBMITTER: Jung HJ

PROVIDER: S-EPMC6580686 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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MicroRNAs in Skeletal Muscle Aging: Current Issues and Perspectives.

Jung Hwa Jin HJ Lee Kwang-Pyo KP Kwon Ki-Sun KS Suh Yousin Y

The journals of gerontology. Series A, Biological sciences and medical sciences 20190601 7

Skeletal muscle is one of the major organs responsible for body movements and metabolism making up approximately 40% of the total body mass. During aging, skeletal muscle exhibits a degenerative age-associated decline in mass and function termed sarcopenia. This age-associated dysfunction of skeletal muscle is a major criterion of morbidity, mortality, and overall declines of quality of life in the elderly people. Therefore, researchers have focused on identifying modulators of muscle aging proc ...[more]

PMID: 30215687

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Project description:With age, adult skeletal muscle (SkM) is known to decrease in muscle mass, strength, and functional capacity, a state known as sarcopenia. Here we developed an in vitro three-dimensional (3D) bioengineered senescent SkM tissue using primary human myoblasts. These tissues exhibited the characteristics of atrophied muscle, including expression of senescent genes, decreased number of satellite cells, reduced number and size of myofibers, and compromised metabolism and calcium flux. As a result, senescent SkM tissues showed impaired ability to generate force in response to electrical stimulation compared with young tissues. Furthermore, in contrast to young SkM tissues, senescent tissues failed to regenerate in response to injury, possibly as a result of persistent apoptosis and failure to initiate a proliferation program. Our findings suggest that 3D senescent SkM may provide a powerful model for studying aging and a platform for drug testing and discovery of therapeutic compounds to improve the function of sarcopenic muscle. Impact statement Skeletal muscle (SkM) plays important physiological roles and has significant regenerative capacity. However, aged SkM lose their functionality and regeneration ability. In this article, we present a senescent human bioengineering SkM tissue model that can be used to investigate senescence, metabolic or genetic diseases that inflict SkM, and to test various strategies including novel small molecules that restore muscle function and promote regeneration. One key limitation of two-dimensional cell culture system is the detachment of contractile myotubes from the surface over time, thereby limiting the evaluation of myogenic function. Here we use primary human myoblasts, which exhibit all major hallmarks of aging to mimic the organization and function of native muscle. Using this system, we were able to measure the contractile function, calcium transients, and regeneration capacity of SkM tissues. We also evaluated the response of senescent SkM tissues to injury and their ability to regenerate and recover, compared with "young" tissues. Our results suggest that three-dimensional constructs enable organization of contractile units including myosin and actin filaments, thereby providing a powerful platform for the quantitative assessment of muscle myotubes in response to injury, genetic or metabolic disorders, or pharmacological testing.

Dataset Information

MicroRNAs in Skeletal Muscle Aging: Current Issues and Perspectives.

Publications

MicroRNAs in Skeletal Muscle Aging: Current Issues and Perspectives.

Similar Datasets

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