scholarly journals Targeting Age-Dependent Functional and Metabolic Decline of Human Skeletal Muscle: The Geroprotective Role of Exercise, Myokine IL-6, and Vitamin D

2020 ◽  
Vol 21 (3) ◽  
pp. 1010 ◽  
Author(s):  
Clara Crescioli

In the elderly, whole-body health largely relies on healthy skeletal muscle, which controls body stability, locomotion, and metabolic homeostasis. Age-related skeletal muscle structural/functional deterioration is associated with a higher risk of severe comorbid conditions and poorer outcomes, demanding major socioeconomic costs. Thus, the need for efficient so-called geroprotective strategies to improve resilience and ensure a good quality of life in older subjects is urgent. Skeletal muscle senescence and metabolic dysregulation share common cellular/intracellular mechanisms, potentially representing targets for intervention to preserve muscle integrity. Many factors converge in aging, and multifaceted approaches have been proposed as interventions, although they have often been inconclusive. Physical exercise can counteract aging and metabolic deficits, not only in maintaining tissue mass, but also by preserving tissue secretory function. Indeed, skeletal muscle is currently considered a proper secretory organ controlling distant organ functions through immunoactive regulatory small peptides called myokines. This review provides a current perspective on the main biomolecular mechanisms underlying age-dependent and metabolic deterioration of skeletal muscle, herein discussed as a secretory organ, the functional integrity of which largely depends on exercise and myokine release. In particular, muscle-derived interleukin (IL)-6 is discussed as a nutrient-level biosensor. Overall, exercise and vitamin D are addressed as optimal geroprotective strategies in view of their multi-target effects.

2013 ◽  
Vol 73 (1) ◽  
pp. 16-33 ◽  
Author(s):  
Ailsa A. Welch

Age-related muscle loss impacts on whole-body metabolism and leads to frailty and sarcopenia, which are risk factors for fractures and mortality. Although nutrients are integral to muscle metabolism the relationship between nutrition and muscle loss has only been extensively investigated for protein and amino acids. The objective of the present paper is to describe other aspects of nutrition and their association with skeletal muscle mass. Mechanisms for muscle loss relate to imbalance in protein turnover with a number of anabolic pathways of which the mechanistic TOR pathway and the IGF-1–Akt–FoxO pathways are the most characterised. In terms of catabolism the ubiquitin proteasome system, apoptosis, autophagy, inflammation, oxidation and insulin resistance are among the major mechanisms proposed. The limited research associating vitamin D, alcohol, dietary acid–base load, dietary fat and anti-oxidant nutrients with age-related muscle loss is described. Vitamin D may be protective for muscle loss; a more alkalinogenic diet and diets higher in the anti-oxidant nutrients vitamin C and vitamin E may also prevent muscle loss. Although present recommendations for prevention of sarcopenia focus on protein, and to some extent on vitamin D, other aspects of the diet including fruits and vegetables should be considered. Clearly, more research into other aspects of nutrition and their role in prevention of muscle loss is required.


Author(s):  
Betsy Szeto ◽  
Chris Valentini ◽  
Anil K Lalwani

ABSTRACT Background The elderly are at increased risk of both hearing loss (HL) and osteoporosis. Bone mineral density (BMD) has been putatively linked to HL. However, the roles of serum calcium concentrations and vitamin D status have yet to be elucidated. Objectives The purpose of this study was to examine the relation between vitamin D status, parathyroid hormone (PTH), total calcium, BMD, and HL in a nationally representative sample of elderly adults. Methods Using the NHANES (2005–2010), audiometry and BMD data of 1123 participants aged ≥70 y were analyzed in a cross-sectional manner. HL was defined as pure tone averages >25 dB HL at 500, 1000, and 2000 Hz (low frequency); 500, 1000, 2000, and 4000 Hz (speech frequency); and 3000, 4000, 6000, and 8000 Hz (high frequency) in either ear. Multivariable logistic regression was used to examine the relation between HL and total 25-hydroxyvitamin D [25(OH)D], PTH, total calcium, and BMD, adjusting for covariates. Results In multivariable analyses, total 25(OH)D < 20 ng/mL was found to be associated with greater odds of low-frequency HL (OR: 2.02; 95% CI: 1.28, 3.19) and speech-frequency HL (OR: 1.96; 95% CI: 1.12, 3.44). A 1-unit decrease in femoral neck BMD (OR: 4.55; 95% CI: 1.28, 16.67) and a 1-unit decrease in total spine BMD (OR: 6.25; 95% CI: 1.33, 33.33) were found to be associated with greater odds of low-frequency HL. Serum PTH and total calcium were not found to be associated with HL. Conclusions In the elderly, low vitamin D status was associated with low-frequency and speech-frequency HL. Low vitamin D status may be a potential risk factor for age-related HL.


2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Mariangela Marrone ◽  
Rita Maria Laura La Rovere ◽  
Simone Guarnieri ◽  
Ester Sara Di Filippo ◽  
Giovanni Monaco ◽  
...  

Sarcopenia is the age-related loss of skeletal muscle mass, strength, and function. It is associated with regenerative difficulties by satellite cells, adult muscle stem cells, and alteration of oxidative management, mainly the increase in superoxide anions (O2•−). We aimed to investigate the relation between regenerative deficit in elderly and increase in O2•− production along with mitochondrial alterations. Myoblasts and myotubes from skeletal muscle of young and elderly healthy subjects (27.8 ± 6 and 72.4 ± 6.5 years old) were measured: (1) superoxide dismutase activity and protein content, (2) mitochondrial O2•− production levels, (3) O2•− production variability, and (4) mitochondrial bioenergetic profile. Compared to young myoblasts, elderly myoblasts displayed decreased SOD2 protein expression, elevated mitochondrial O2•− baseline levels, and decreased oxidative phosphorylation and glycolysis. Additionally, elderly versus young myotubes showed elevated mitochondrial O2•− levels when stressed with N-acetyl cysteine or high glucose and higher glycolysis despite showing comparable oxidative phosphorylation levels. Altogether, the elderly may have less metabolic plasticity due to the impaired mitochondrial function caused by O2•−. However, the increased energy demand related to the differentiation process appears to activate compensatory mechanisms for the partial mitochondrial dysfunction.


Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984
Author(s):  
Galya Bigman

Smell and taste decline with aging, and markedly deteriorate when nutritional deficiencies occur. This study aims to examine the associations between Vitamin D (VD) deficiency and smell and taste impairments among adults. This paper details a cross-sectional study utilizing data from the US National Health and Nutrition Examination Survey (NHANES, 2013–2014.). Smell impairment was assessed by the Pocket Smell Test and defined as failing to correctly identify six or more of the eight odors. Taste impairment was defined as failing to correctly identify quinine or sodium chloride. VD was measured as serum 25-hydroxyvitamin. Multivariable weighted logistic regressions were utilized. Adjusted odds ratio (OR) and 95% confidence interval (CI) were presented. Overall, 2216 (smell sample) and 2636 (taste sample) participants were included, aged between 40 and 80 years old. Of those, 18.3% had taste impairment, 12.2% had smell impairment, and 20% had VD deficiency (<20 ng/mL). Compared to participants with sufficient VD (>30 ng/mL), those with VD deficiency were more likely by 39% to report a higher prevalence of smell impairment (OR = 1.39, 95%CI: 1.02–1.89); and only participants aged 70–80 years with VD inadequacy (20–30 ng/mL) were more likely by 96% to report a higher prevalence of taste impairment (OR = 1.96, 95%CI: 1.35–1.85). VD may have a significant role in age-related smell impairment in adults aged 40 years or older, and in age-related taste impairment in the elderly aged 70–80 years.


2019 ◽  
Vol 97 (4) ◽  
pp. 328-334 ◽  
Author(s):  
Mirna N. Chahine ◽  
Simon Toupance ◽  
Sandy El-Hakim ◽  
Carlos Labat ◽  
Sylvie Gautier ◽  
...  

Short telomere length (TL) is associated with atherosclerotic cardiovascular disease (ACVD) and other age-related diseases. It is unclear whether these associations originate from having inherently short TL or a faster TL attrition before or during disease development. We proposed the blood-and-muscle model to assess TL dynamics throughout life course. Our objective was to measure TL in leukocytes (LTL) and in skeletal muscle (MTL), which served as a proxy of TL at birth. The delta (MTL–LTL) represented life-long telomere attrition. Blood draws and skeletal muscle biopsies were performed on 35 Lebanese individuals undergoing surgery. Following DNA extraction, LTL and MTL were measured by Southern blot. In every individual aged between 30 and 85 years, MTL was longer than LTL. With age, MTL and LTL decreased, but the delta (MTL–LTL) increased by 14 bp/year. We validated the blood-and-muscle model that allowed us to identify TL, TL at birth, and lifelong TL attrition in a cross-sectional study. This model can be used in larger cross-sectional studies to evaluate the association of telomere dynamics with age-related diseases onset and progression.


Author(s):  
Chen He ◽  
Wenzhen He ◽  
Jing Hou ◽  
Kaixuan Chen ◽  
Mei Huang ◽  
...  

Osteoporosis and sarcopenia are two age-related diseases that affect the quality of life in the elderly. Initially, they were thought to be two independent diseases; however, recently, increasing basic and clinical data suggest that skeletal muscle and bone are both spatially and metabolically connected. The term “osteosarcopenia” is used to define a condition of synergy of low bone mineral density with muscle atrophy and hypofunction. Bone and muscle cells secrete several factors, such as cytokines, myokines, and osteokines, into the circulation to influence the biological and pathological activities in local and distant organs and cells. Recent studies reveal that extracellular vesicles containing microRNAs derived from senescent skeletal muscle and bone cells can also be transported and aid in regulating bone-muscle crosstalk. In this review, we summarize the age-related changes in the secretome and extracellular vesicle-microRNAs secreted by the muscle and bone, and discuss their interactions between muscle and bone cells during aging.


1993 ◽  
Vol 18 (4) ◽  
pp. 331-358 ◽  
Author(s):  
Timothy J. Doherty ◽  
Anthony A. Vandervoort ◽  
William F. Brown

This review briefly summarizes the current state of knowledge regarding age related changes in skeletal muscle, followed by a more in-depth review of ageing effects on animal and human motor units (MUs). Ageing in humans is generally associated with reductions in muscle mass (atrophy), leading to reduced voluntary and electrically evoked contractile strength by the 7th decade for most muscle groups studied. As well, contraction and one-half relaxation times are typically prolonged in muscles of the elderly. Evidence from animal and human studies points toward age associated MU loss as the primary mechanism for muscle atrophy, and such losses may be greatest among the largest and fastest MUs. However, based on studies in animals and humans, it appears that at least some of the surviving MUs are able to partially compensate for MU losses, as indicated by an increase in the average MU size with age. The fact that muscles in the elderly have fewer, but on average larger and slower, MUs has important implications for motor control and function in this population. Key words: skeletal muscle, motor neuron, motor axon, contractile properties, adaptation


2003 ◽  
Vol 88 (1) ◽  
pp. 185-191 ◽  
Author(s):  
Reinhold Vieth ◽  
Yasmin Ladak ◽  
Paul G. Walfish

Vitamin D requirements are thought to vary with age, but there is little comparative evidence for this. One goal in establishing a vitamin D requirement is to avoid secondary hyperparathyroidism. We studied 1741 euthyroid, thyroid clinic outpatients without evidence of calcium abnormalities, ranging in age from 19 to 97 yr, whose serum and urine had been analyzed for calcium, vitamin D, and parathyroid status. We found no effect of age on the 25-hydroxyvitamin D [25(OH)D] concentration associated with specific vitamin D intakes, and there was no relationship between 25(OH)D and 1,25hydroxyvitamin D [1,25(OH)2D]. In every age group, serum 1,25(OH)2D declined with increasing creatinine (P &lt; 0.001). What changed with age included creatinine, which correlated with 25(OH)D (r = 0.146, P &lt; 0.001) only in the youngest age group (19–50 yr) but not in the older age groups (P &gt; 0.1). Creatinine did not correlate with PTH in the youngest age group, but the relationship became significant as age increased (e.g. for the elderly, r = 0.365, P &lt; 0.001). Linear regression of log PTH vs. log 25(OH)D agreed with the natural shape of the relationship observed with scatterplot smoothing, and this showed no plateau in PTH as 25(OH)D increased. We compared PTH concentrations among age groups, based on 20 nmol/liter increments in 25(OH)D. Mean PTH in adults older than 70 yr was consistently higher than in adults younger than 50 yr (P &lt; 0.05 by ANOVA and Dunnett’s t test). PTH levels of the elderly who had 25(OH)D concentrations greater than 100 nmol/liter matched PTH of younger adults having 25(OH)D concentrations near 70 nmol/liter. This study shows that all age groups exhibit a high prevalence of 25(OH)D insufficiency and secondary hyperparathyroidism. Older adults are just as efficient in maintaining 25(OH)D, but they need more vitamin D to produce the higher 25(OH)D concentrations required to overcome the hyperparathyroidism associated with their diminishing renal function.


2009 ◽  
Vol 94 (8) ◽  
pp. 2880-2886 ◽  
Author(s):  
Pamela U. Freda ◽  
Wei Shen ◽  
Carlos M. Reyes-Vidal ◽  
Eliza B. Geer ◽  
Fernando Arias-Mendoza ◽  
...  

Context: GH and IGF-I are nitrogen retaining and anabolic, but the impact of long-term exposure to supraphysiological GH and IGF-I, either from endogenous overproduction in acromegaly or exogenous sources, on skeletal muscle (SM) mass is not clear. Objectives: The objectives of the study were to assess SM mass by whole-body magnetic resonance imaging (MRI) in acromegaly and test the hypothesis that dual-energy x-ray absorptiometry (DXA) lean tissue mass-derived estimates of SM accurately estimate true SM mass. Design, Setting, and Patients: The design was a cross-sectional study in 27 acromegaly patients compared with predicted models developed in 315 nonacromegaly subjects and to matched controls. Outcome Measures: Mass of SM from whole-body MRI and lean tissue from DXA were measured. Results: SM mass did not differ from predicted or control values in active acromegaly: 31.75 ± 8.6 kg (acromegaly) vs. 33.06 ± 8.9 kg (predicted); SM was 95.6 ± 12.8% of predicted (range 66.7–122%) (P = 0.088). Lean tissue mass (DXA) was higher in acromegaly than controls: 65.91 ± 15.2 vs. 58.73 ± 13.5 kg (P &lt; 0.0001). The difference between lean tissue mass (DXA) and SM in acromegaly patients was higher than that in controls (P &lt; 0.0001) consistent with an enlarged non-SM lean compartment in acromegaly. SM mass predicted by DXA correlated highly with SM mass by MRI (r = 0.97, P &lt; 0.0001). SM (MRI) to SM (DXA predicted) ratio was 1.018 (range 0.896–1.159), indicating high agreement of these measures of SM. Conclusions: SM mass in active acromegaly patients did not differ from predicted values. SM mass estimated from DXA agreed highly with SM by MRI, supporting the validity of the DXA model in assessing SM in acromegaly and other disorders of GH/IGF-I secretion.


2006 ◽  
Vol 291 (6) ◽  
pp. F1177-F1183 ◽  
Author(s):  
Monique van Abel ◽  
Sylvie Huybers ◽  
Joost G. J. Hoenderop ◽  
Annemiete W. C. M. van der Kemp ◽  
Johannes P. T. M. van Leeuwen ◽  
...  

Aging is associated with alterations in Ca2+ homeostasis, which predisposes elder people to hyperparathyroidism and osteoporosis. Intestinal Ca2+ absorption decreases with aging and, in particular, active transport of Ca2+ by the duodenum. In addition, there are age-related changes in renal Ca2+ handling. To examine age-related changes in expression of the renal and intestinal epithelial Ca2+ channels, control (TRPV5+/+) and TRPV5 knockout (TRPV5−/−) mice aged 10, 30, and 52 wk were studied. Aging of TRPV5+/+ mice resulted in a tendency toward increased renal Ca2+ excretion and significantly decreased intestinal Ca2+ absorption, which was accompanied by reduced expression of TRPV5 and TRPV6, respectively, despite increased serum 1,25(OH)2D3 levels. Similarly, in TRPV5−/− mice the existing renal Ca2+ loss was more pronounced in elder animals, whereas the compensatory intestinal Ca2+ absorption and TRPV6 expression declined with aging. In both mice strains, aging resulted in a resistance to 1,25(OH)2D3 and diminished renal vitamin D receptor mRNA levels, whereas serum Ca2+ levels remained constant. Furthermore, 52-wk-old TRPV5−/− mice showed severe hyperparathyroidism, whereas PTH levels in elder TRPV5+/+ mice remained normal. In 52-wk-old TRPV5−/− mice, serum osteocalcin levels were increased in accordance with the elevated PTH levels, suggesting an increased bone turnover in these mice. In conclusion, downregulation of TRPV5 and TRPV6 is likely involved in the impaired Ca2+ (re)absorption during aging. Moreover, TRPV5−/− mice likely develop age-related hyperparathyroidism and osteoporotic characteristics before TRPV5+/+ mice, demonstrating the importance of the epithelial Ca2+ channels in Ca2+ homeostasis.


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