Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males
TL;DR: Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms to attenuate adverse metabolic and functional outcomes.
Abstract: Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes.
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TL;DR: There is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women.
Abstract: Women have less muscle than men but lose it more slowly during aging. To discover potential underlying mechanism(s) for this we evaluated the muscle protein synthesis process in postabsorptive conditions and during feeding in twenty-nine 65–80 year old men (n = 13) and women (n = 16). We discovered that the basal concentration of phosphorylated eEF2Thr56 was ∼40% less (P<0.05) and the basal rate of MPS was ∼30% greater (P = 0.02) in women than in men; the basal concentrations of muscle phosphorylated AktThr308, p70s6kThr389, eIF4ESer209, and eIF4E-BP1Thr37/46 were not different between the sexes. Feeding increased (P<0.05) AktThr308 and p70s6kThr389 phosphorylation to the same extent in men and women but increased (P<0.05) the phosphorylation of eIF4ESer209 and eIF4E-BP1Thr37/46 in men only. Accordingly, feeding increased MPS in men (P<0.01) but not in women. The postabsorptive muscle mRNA concentrations for myoD and myostatin were not different between sexes; feeding doubled myoD mRNA (P<0.05) and halved that of myostatin (P<0.05) in both sexes. Thus, there is sexual dimorphism in MPS and its control in older adults; a greater basal rate of MPS, operating over most of the day may partially explain the slower loss of muscle in older women.
129 citations
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TL;DR: Subjects with AD, even the early stages of AD, showed a high prevalence rate of sarcopenia and there were differences in muscle functions and physical performance between the stages of the female and male AD.
Abstract: Although sarcopenia is closely linked to dementia, particularly Alzheimer disease (AD), there are few studies examining the prevalence and associated factors of sarcopenia in subjects with AD. This study aimed to investigate the prevalence of sarcopenia, factors associated with sarcopenia in elderly subjects with AD, and differences in muscle functions of the upper and lower extremities and gait speed at various stages of AD. We evaluated handgrip and knee extension strength, muscle mass, and gait speed in 285 elderly outpatients with probable AD (mean age 82. 0 ± 5.3 years), including early AD (n = 82), mild AD (n = 90), and moderate AD (n = 113), and 67 elderly outpatients with normal cognition (NC) (mean age 81.1 ± 4.7 years). Sarcopenia was defined according to the consensus of the Asian Working Group for Sarcopenia. The prevalence rate of sarcopenia was significantly higher in early AD, mild AD, and moderate AD than in NC (11% in NC, 36% in early AD, 45% in mild AD, and 60% in moderate AD of the female group, and 13% in NC, 41% in early AD, 47% in mild AD, and 47% in moderate AD of the male group). Age, body mass index, and Mini-mental state examination score were associated with sarcopenia in female or male AD groups. Decreased muscle strength without loss of muscle mass of the upper and lower extremities in the female AD group and those of the lower extremity in the AD male group were found in early and mild stages. Both muscle strength and mass decreased in the moderate AD. Low gait speed was also found in the early female and male AD which progressed with advancing dementia. Subjects with AD, even the early stages of AD, showed a high prevalence rate of sarcopenia. Higher age, lower BMI, and lower MMSE score were associated with sarcopenia in the female or male AD. There were differences in muscle functions and physical performance between the stages of the female and male AD.
87 citations
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TL;DR: Cognitive factors modulate the representation of the reward value of taste, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex, which are important in the control of appetite and food intake.
Abstract: The taste cortex in the anterior insula provides separate and combined representations of the taste, temperature, and texture of food in the mouth independently of hunger and thus of reward value and pleasantness. One synapse on, in the orbitofrontal cortex, these sensory inputs are combined by associative learning with olfactory and visual inputs for some neurons, and these neurons encode food reward value in that they respond to food only when hunger is present and in that activations correlate linearly with subjective pleasantness. Cognitive factors, including word-level descriptions and selective attention to affective value, modulate the representation of the reward value of taste, olfactory, and flavor stimuli in the orbitofrontal cortex and a region to which it projects, the anterior cingulate cortex. These food reward representations are important in the control of appetite and food intake. Individual differences in reward representations may contribute to obesity, and there are age-related differences in these reward representations. Implications of how reward systems in the brain operate for understanding, preventing, and treating obesity are described.
67 citations
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TL;DR: The role for autophagy in particular mitochondrial selective autophagic namely mitophagy is summarized in the benefit versus risk of physical exercise on cardiovascular function.
Abstract: Physical exercise promotes cardiorespiratory fitness, and is considered the mainstream of non-pharmacological therapies along with lifestyle modification for various chronic diseases, in particular cardiovascular diseases. Physical exercise may positively affect various cardiovascular risk factors including body weight, blood pressure, insulin sensitivity, lipid and glucose metabolism, heart function, endothelial function, and body fat composition. With the ever-rising prevalence of obesity and other types of metabolic diseases, as well as sedentary lifestyle, regular exercise of moderate intensity has been indicated to benefit cardiovascular health and reduce overall disease mortality. Exercise offers a wide cadre of favorable responses in the cardiovascular system such as improved dynamics of the cardiovascular system, reduced prevalence of coronary heart diseases and cardiomyopathies, enhanced cardiac reserve capacity, and autonomic regulation. Ample clinical and experimental evidence has indicated an emerging role for autophagy, a conservative catabolism process to degrade and recycle cellular organelles and nutrients, in exercise training-offered cardiovascular benefits. Regular physical exercise as a unique form of physiological stress is capable of triggering adaptation while autophagy in particular selective autophagy seems to be permissive to such cardiovascular adaptation. Here in this mini-review, we will summarize the role for autophagy in particular mitochondrial selective autophagy namely mitophagy in the benefit versus risk of physical exercise on cardiovascular function.
65 citations
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Mahsa Eskian1, Mahsa Eskian2, Abass Alavi3, MirHojjat Khorasanizadeh2, MirHojjat Khorasanizadeh1, Benjamin L. Viglianti4, Hans Jacobsson5, Tara Barwick6, Tara Barwick7, Alipasha Meysamie1, Sun K. Yi8, Shingo Iwano9, Bohdan Bybel10, Federico Caobelli11, Filippo Lococo, Joaquim Gea, Antonio Sancho-Muñoz, Jukka Schildt12, Ebru Tatcı, Constantin Lapa, Georgia Keramida13, Mike Peters14, Raef R. Boktor15, Joemon John, Alexander G Pitman16, Tomasz Mazurek17, Nima Rezaei1, Nima Rezaei2 •
Tehran University of Medical Sciences1, Education and Research Network2, University of Pennsylvania3, University of Michigan4, Karolinska Institutet5, Imperial College London6, Imperial College Healthcare7, University of Arizona8, Nagoya University9, University of Manitoba10, University Hospital of Basel11, Helsinki University Central Hospital12, Harefield Hospital13, Brighton and Sussex University Hospitals NHS Trust14, St John of God Health Care15, University of Notre Dame16, Medical University of Warsaw17
TL;DR: If BGL is lower than 200 mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest, and future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.
Abstract: To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in 18F-FDG-PET scan. A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, 18F-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups ( 200 mg/dl). Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p 200 mg/dl had significantly lower SUVmax. If BGL is lower than 200 mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.
57 citations
References
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TL;DR: A molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1, is demonstrated and a signalling mechanism for UlK1 regulation and autophagic induction in response to nutrient signalling is revealed.
Abstract: Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.
5,314 citations
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TL;DR: This work has shown that abdominal obesity — the most prevalent manifestation of metabolic syndrome — is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis.
Abstract: Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.
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TL;DR: To establish the prevalence of sarc Openia in older Americans and to test the hypothesis that sarcopenia is related to functional impairment and physical disability in older persons is established.
Abstract: OBJECTIVES: To establish the prevalence of sarcopenia in older Americans and to test the hypothesis that sarcope- nia is related to functional impairment and physical dis- ability in older persons. DESIGN: Cross-sectional survey. SETTING: Nationally representative cross-sectional sur- vey using data from the Third National Health and Nutri- tion Examination Survey (NHANES III). PARTICIPANTS: Fourteen thousand eight hundred eigh- teen adult NHANES III participants aged 18 and older. MEASUREMENTS: The presence of sarcopenia and the relationship between sarcopenia and functional impairment and disability were examined in 4,504 adults aged 60 and older. Skeletal muscle mass was estimated from bioimped- ance analysis measurements and expressed as skeletal mus- cle mass index (SMIskeletal muscle mass/body mass � 100). Subjects were considered to have a normal SMI if their SMI was greater than -one standard deviation above the sex-specific mean for young adults (aged 18-39). Class I sarcopenia was considered present in subjects whose SMI was within -one to -two standard deviations of young adult values, and class II sarcopenia was present in subjects whose SMI was below -two standard deviations of young adult values. RESULTS: The prevalence of class I and class II sarcope- nia increased from the third to sixth decades but remained relatively constant thereafter. The prevalence of class I (59% vs 45%) and class II (10% vs 7%) sarcopenia was greater in the older ( � 60 years) women than in the older men ( P � .001). The likelihood of functional impairment and disability was approximately two times greater in the older men and three times greater in the older women with class II sarcopenia than in the older men and women with a normal SMI, respectively. Some of the associations be- tween class II sarcopenia and functional impairment re- mained significant after adjustment for age, race, body mass index, health behaviors, and comorbidity. CONCLUSIONS: Reduced relative skeletal muscle mass in older Americans is a common occurrence that is signifi- cantly and independently associated with functional im- pairment and disability, particularly in older women. These observations provide strong support for the prevailing view that sarcopenia may be an important and potentially re- versible cause of morbidity and mortality in older persons. J Am Geriatr Soc 50:889-896, 2002.
2,710 citations
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Roger A. Fielding1, Bruno Vellas2, William J. Evans3, Shalender Bhasin4, John E. Morley5, Anne B. Newman6, Gabor Abellan van Kan, Sandrine Andrieu2, Juergen M. Bauer7, Denis Breuille8, Tommy Cederholm9, Julie Chandler10, Capucine De Meynard, Lorenzo M. Donini11, Tamara B. Harris12, Aimo Kannt, Florence Keime Guibert, Graziano Onder, Dimitris Papanicolaou10, Yves Rolland, Daniel Rooks13, Cornel C. Sieber, Elisabeth Souhami, Sjors Verlaan, Mauro Zamboni14 •
United States Department of Agriculture1, French Institute of Health and Medical Research2, Research Triangle Park3, Boston University4, Saint Louis University5, University of Pittsburgh6, University of Erlangen-Nuremberg7, Nestlé8, Uppsala University9, Merck & Co.10, Sapienza University of Rome11, National Institutes of Health12, Novartis13, University of Verona14
TL;DR: Sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health, and patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry with sarcopenia being defined using currently validated definitions.
2,378 citations
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TL;DR: It is indicated that men have more SM than women and that these gender differences are greater in the upper body.
Abstract: We employed a whole body magnetic resonance imaging protocol to examine the influence of age, gender, body weight, and height on skeletal muscle (SM) mass and distribution in a large and heterogene...
2,361 citations