Role of microRNAs in the age-related changes in skeletal muscle and diet or exercise interventions to promote healthy aging in humans

During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, the age-related changes in rates of synthetic and degradative processes are less well understood. In the present study we measured rates of collagen synthesis in vivo using a flooding dose of unlabelled proline given with [14C]proline and determining production of hydroxy[14C]proline. Degradation of newly synthesized collagen was estimated from the amount of free hydroxy [14C]proline in tissues 30 min after injection. Collagen fractional synthesis rates ranged from about 5%/day in skeletal muscle to 20%/day in hearts of rats aged 1 month. At 15 months of age, collagen fractional synthesis rates had decreased markedly in lung and skin, but in skeletal muscle and heart, rates were unchanged. At 24 months of age, synthesis rates had decreased by at least 10-fold in all tissues, compared with rates at 1 month. The proportion of newly synthesized collagen degraded ranged from 6.4 +/- 0.4% in skin to 61.6 +/- 5.0% in heart at 1 month of age. During aging the proportion degraded increased in all tissues to maximal values at 15 months, ranging from 56 +/- 7% in skin to 96 +/- 1% in heart. These data suggest that there are marked age-related changes in rates of collagen metabolism. They also indicate that synthesis is active even in old animals, where the bulk of collagens produced are destined to be degraded.

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Age-Related Changes in Hormone Action: The Role of Hormone Receptors

Endocrine and Neuroendocrine Mechanisms of Aging ◽

10.1201/9781315150956-4 ◽

2017 ◽

pp. 51-75

Author(s):

George S. Roth

Keyword(s):

Hormone Receptors ◽

Hormone Action ◽

Age Related ◽

Age Related Changes

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Advances in the Role of Leucine-Sensing in the Regulation of Protein Synthesis in Aging Skeletal Muscle

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.646482 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yan Zhao ◽

Jason Cholewa ◽

Huayu Shang ◽

Yueqin Yang ◽

Xiaomin Ding ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Therapeutic Potential ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Trna Synthetase ◽

Limiting Factor ◽

Anabolic Resistance ◽

Age Related

Skeletal muscle anabolic resistance (i.e., the decrease in muscle protein synthesis (MPS) in response to anabolic stimuli such as amino acids and exercise) has been identified as a major cause of age-related sarcopenia, to which blunted nutrition-sensing contributes. In recent years, it has been suggested that a leucine sensor may function as a rate-limiting factor in skeletal MPS via small-molecule GTPase. Leucine-sensing and response may therefore have important therapeutic potential in the steady regulation of protein metabolism in aging skeletal muscle. This paper systematically summarizes the three critical processes involved in the leucine-sensing and response process: (1) How the coincidence detector mammalian target of rapamycin complex 1 localizes on the surface of lysosome and how its crucial upstream regulators Rheb and RagB/RagD interact to modulate the leucine response; (2) how complexes such as Ragulator, GATOR, FLCN, and TSC control the nucleotide loading state of Rheb and RagB/RagD to modulate their functional activity; and (3) how the identified leucine sensor leucyl-tRNA synthetase (LARS) and stress response protein 2 (Sestrin2) participate in the leucine-sensing process and the activation of RagB/RagD. Finally, we discuss the potential mechanistic role of exercise and its interactions with leucine-sensing and anabolic responses.

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Role of Age-Related Mitochondrial Dysfunction in Sarcopenia

International Journal of Molecular Sciences ◽

10.3390/ijms21155236 ◽

2020 ◽

Vol 21 (15) ◽

pp. 5236 ◽

Cited By ~ 1

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.

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