  skeletal muscle contractions power human body movements and are essential for maintaining stability . skeletal muscle tissue accounts for almost half of the human body mass and , in addition to its power - generating role , is a crucial factor in maintaining homeostasis .
given its central role in human mobility and metabolic function , any deterioration in the contractile , material , and metabolic properties of skeletal muscle has an extremely important effect on human health .
aging is associated with a progressive decline of muscle mass , quality , and strength , a condition known as sarcopenia .
the term sarcopenia , coined by i. h. rosenberg , originates from the greek words sarx ( flesh ) and penia ( loss ) .
although this term is applied clinically to denote loss of muscle mass , it is often used to describe both a set of cellular processes ( denervation , mitochondrial dysfunction , inflammatory , and hormonal changes ) and a set of outcomes such as decreased muscle strength , decreased mobility and function , increased fatigue , a greater risk of falls , and reduced energy needs . in addition , reduced muscle mass in aged individuals has been associated with decreased survival rates following critical illness . in most countries ,
there has been a rapid and continuing increase in life expectancy . by the year 2030
in the 27 member states of the eu , the percentage of people aged 65 years and older will rise from 17.1 in 2008 to 25.4 in 2035 and to 30 in 2060 .
the estimated direct healthcare costs attributable to sarcopenia in the usa in 2000 were $ 18.5 billion ( $ 10.8 billion in men and $ 7.7 billion in women ) , which represented about 1.5% of total healthcare expenditures for that year .
therefore , age - related losses in skeletal muscle mass and function present an extremely important current and future public health issue .   
lean muscle mass generally contributes up to ~50% of total body weight in young adults but declines with aging to be 25% at 7580  years  old [ 9 , 10 ] .
the loss of muscle mass is most notable in the lower limb muscle groups , with the cross - sectional area of the vastus lateralis being reduced by as much as 40% between the age of 20 and 80  years . on a muscle fiber level
, sarcopenia is characterized by specific type ii muscle fiber atrophy , fiber necrosis , and fiber - type grouping [ 1113 ] . in elderly men , verdijk et al
.   showed a reduction in type ii muscle fiber satellite cell content with aging .
although various investigators showed very contradicting results for age - dependent changes of satellite cell numbers [ 1316 ] , most studies point to an age - dependent reduction in muscle regenerative capacity due to reduced satellite cell proliferation and differentiation .   
another morphologic aspect of sarcopenia is the infiltration of muscle tissue components by lipids because of the increased frequency of adipocyte or lipid deposition [ 17 , 18 ] within muscle fibers . as with precursor cells in bone marrow , liver , and kidney , muscle satellite cells that can express an adipocytic phenotype increase with age ,
although this process is still relatively poorly understood in terms of its extent and spatial distribution .
lipid deposition , often referred to as intramyocellular lipid , may result from a net buildup of lipids due to the reduced oxidative capacity of muscle fibers with aging [ 17 , 20 ] .  
several possible mechanisms for age - related muscle atrophy have been described ; however , the precise contribution of each is unknown .
age - related muscle loss is a result of reductions in the size and number of muscle fibers   possibly due to a multifactorial process that involves physical activity , nutritional intake , oxidative stress , and hormonal changes [ 3 , 22 ] .
the specific contribution of each of these factors is unknown , but there is emerging evidence that the disruption of several positive regulators ( akt and serum response factor ) of muscle hypertrophy with age is an important feature in the progression of sarcopenia [ 23 , 24 ] .  
obesity is currently epidemic in the usa , with almost 70% of americans overweight and one of three obese .
obesity is associated with increased morbidity and mortality , and there is unchallenged evidence that obesity increases the risk for the development of hypertension , dyslipidemia , type 2 diabetes mellitus , sleep apnea , cancers of the breast , prostate , and colon , and all - cause mortality [ 2628 ] .
  aging is associated with important changes in body composition and metabolism [ 29 , 30 ] . between the age of 20 and 70 years
, there is a progressive decrease of fat - free mass ( mainly muscle ) of about 40% and a rise in fat mass .
there is a relatively greater decrease in peripheral compared to central fat - free mass .
after the age of 70 years , fat - free mass and fat mass decrease in parallel .
fat distribution changes with age such that there is an increase in visceral fat , which is more marked in women than in men . also , fat is increasingly deposited in skeletal muscle and in the liver .
the higher visceral fat is the main determinant of impaired glucose tolerance in the elderly . increased intramuscular and intrahepatic fat contribute to impaired insulin action through locally released adipokines and fat - free fatty acids . increased pancreatic fat with declining -cell function
also plays a role .   due to the loss of skeletal muscle , the basal metabolic rate declines by 2%-3% per decade after the age of 20 years , by 4% per decade after the age of 50 years , equating approximately 150  kcal per day , and overall by 30% between the age of 20 and 70 years .
this , together with decreased intensity and duration of physical activity as well as decreased postprandial energy expenditure due to a decreased fat oxidation , accounts for the decreased energy expenditure seen with aging .
medical complications of obesity in the elderly are mainly concentrated around the metabolic syndrome ( with glucose intolerance , hypertension , dyslipidaemia , and cardiovascular disease ) .
the metabolic syndrome peaks at the age of 5070 years in males and of 6080 years .
the metabolic syndrome is a recognized risk factor for strole but is also related to subclinical ischaemic brain lesions , placing the subjects at risk for future cognitive impairment .
obesity also increases the risk of heart failure , and estimates suggest that having a body mass index ( bmi ) > 30  kg / m doubles the risk . other obesity - related disorders are osteoarthritis , pulmonary dysfunction such as the obstructive sleep apnoea syndrome , certain cancer types , reduced cognitive skills , and urinary incontinence [ 6 , 36 , 37 ] .   
the obesity elderly are also likely to have functional limitations because of the decreased muscle mass and strength and increased join dysfunction , disabilities of activities of daily living , frailty , chronic pain , and impaired quality of life [ 6 , 38 ] .
indeed , baumgartner   observed that men and women older than 60 years of age with sarcopenic obesity showed , respectively , an 8- and 11-fold higher risk of having three or more physical disabilities .
more importantly , it was observed that the association with functional status impairment was stronger for sarcopenic obesity than for either obesity or sarcopenia alone .
obesity is an important risk for frailty either through increased levels of inflammatory markers or through sarcopenia .  
interestingly , the proposed mechanism involved in sarcopenic obesity could be the increased production from adipose tissue of different substances , such as tumor necrosis factor- ( tnf- ) and leptin , which are known to influence insulin resistance and growth hormone ( gh ) secretion .
this hypothesis has been confirmed by schrager et al .   who observed in a large - scale sample of men and women that the degree of obesity , as evaluated by bmi and its distribution , and by waist circumference , directly affected inflammation which in turn contributed to the development and progression of sarcopenia .
further increases in leptin , at least partially depending on the age - related fat mass increase , may lead to leptin resistance and thus to a reduction of fatty acid oxidation in muscles , contributing to ectopic fat deposition in organs such as the liver , heart , and muscles   and , in turn , to the loss of muscle quality in obese older subjects .   
studies in both humans and animals demonstrate that obesity is a state of low - grade , chronic inflammation , characterized by elevated circulating proinflammatory molecules produced predominantly from enlarged adipocytes and activated macrophages in adipose tissue [ 45 , 46 ] .
lipocalin-2 would be a possible candidate regulating the amount of adipose tissue under chronic inflammation and insulin resistance .
expression of lipocalin-2 in adipose tissue is elevated in various experimental models of obesity and in obese humans [ 4951 ] .
its expression can be induced by various inflammatory stimuli , including lipopolysaccharides and interleukin ( il)-1 [ 52 , 53 ] .
intriguingly , lipocalin-2 deficiency in mice elicits marked decreases in the expression and the activity of 12-lipoxygenase , an enzyme responsible for metabolizing arachidonic acid , and the production of tnf- , a critical insulin resistance - inducing factor .
it remains to be elucidated whether lipocalin-2 levels increase with normal aging and further with sarcopenic obesity in mammals .
  testosterone increases muscle protein synthesis , and its effects on muscle are modulated by several factors including genetic background , nutrition , and exercise . in males , levels of testosterone decrease by 1% per year and those of bioavailable testosterone by 2% per year from age 30 [ 57 , 58 ] . in women ,
gh is a single - chain peptide of 191 amino acids produced and secreted mainly by the somatotrophs of the anterior pituitary gland .
gh secretion occurs in a pulsatile manner with a major surge at the onset of a slow - wave sleep and less conspicuous secretory episodes a few hours after meals .
the secretion of gh is maximal at puberty accompanied by very high circulating insulin - like growth factor - i ( igf - i ) levels , with a gradual decline during adulthood .
indeed , circulating gh levels decline progressively after 30 years of age at a rate of ~1% per year . in aged men ,
therefore , many researchers have indicated age - related endocrine defects such as decreases in anabolic hormones . although hormonal supplementation for the elderly has been conducted on a large scale , it was found not to be effective against sarcopenia and to have minor side effects [ 6467 ] .  
increased adiposity is often associated with high circulating levels of free fatty acids [ 68 , 69 ] , which inhibit gh production and decrease plasma levels of igf - i [ 70 , 71 ] .
a recent study showed that sarcopenic obese persons had depressed gh secretion compared to obese persons .
low levels of these anabolic hormones have been reported to be positively associated with low muscle strength [ 74 , 75 ] and may therefore contribute to muscle impairment in obese individuals .   
insulin was infused directly into the femoral artery to increase the leg insulin levels to approximate postprandial values while avoiding systemic hypoaminoacidemia .
there was no significant change in muscle protein breakdown as measured by two- and three - pool modeling .
the increase in synthesis in young subjects resulted in a shift from a negative to positive protein net balance across the leg - indicating overall net protein accretion during the clamp in young subjects . in the older subjects ,
insulin resistance has been long recognized as a characteristic of aging in humans and rodents .
blood flow was lower in older as compared to younger subjects at baseline and during the clamp and tended to increase from baseline in young adults only during the clamp .
as hypothesized by  timmerman and volpi , this effect was likely mediated through insulin - induced vasodilation .
insulin is a potent stimulator of the endothelial - derived vasodilator and nitric oxide . in a subsequent study
, they reported that this age - related insulin resistance of muscle protein synthesis could be overcome by increasing insulin levels to approximately double the postprandial levels via improvements in mammalian target of rapamycin signaling .   
available experimental evidence points to the development of adiposity as the main cause of the decreased insulin action in old rats   and elderly humans [ 83 , 84 ] .
studies in rats have demonstrated that fat mass accretion occurs at early aging and is paralleled by a marked decrease of insulin action in visceral fat tissue .   
inflammation may negatively influence skeletal muscle through direct catabolic effects or through indirect mechanisms ( i.e. , decreases in gh and igf - i concentrations , induction of anorexia , etc . ) .
there is growing evidence that higher levels of inflammatory markers are associated with physical decline in older individuals , possibly through the catabolic effects of these markers on muscle . in an observational study of more than 2000 men and women
the impact of inflammation on the development of sarcopenia is further supported by a recently published animal study showing that a reduction in low - grade inflammation by ibuprofen in old ( 20 months ) animals resulted in a significant decrease in muscle mass loss .
an age - related disruption of the intracellular redox balance appears to be a primary causal factor for a chronic state of low - grade inflammation .
more recently , chung et al .   hypothesized that abundant nuclear factor-b ( nf-b ) protein - induced age - related increases in il-6 and tnf-. moreover , reactive oxygen species ( ros ) also appear to function as second messengers for tnf- in skeletal muscle , activating nf-b either directly or indirectly .
indeed , marked production of ros has been documented in muscle of the elderly [ 90 , 91 ] .
however , it is not clear whether nf-b signaling is enhanced with age . despite some evidence supporting enhanced nf-b signaling in type i fibers of aged skeletal muscle , direct evidence for increased activation and dna binding of nf-b is lacking [ 92 , 93 ] .
for example , philips and leeuwenburgh   found that neither p65 protein expression nor the binding activity of nf-b was significantly altered in the vastus lateralis muscles of 26-month - old rats despite the marked upregulation of tnf- expression in both blood and muscle .
upregulated tnf- expression in serum and muscle seems to enhance apoptosis in mitochondria resulting in a loss of muscle fibers [ 9395 ] .
it has been shown that tnf- is one of the primary signals inducing apoptosis in muscle .   
il-6 and crp , known as  geriatric cytokines  , are multifunctional cytokine produced in situations of trauma , stress , and infection . during the aging process , levels of
the natural production of cytokines is likely beneficial during inflammation , but the overproduction and the maintaining of an inflammatory state for long periods of time , as seen in elderly individuals , is detrimental [ 96 , 97 ] .
a number of authors have demonstrated that a rise in plasma levels of proinflammatory cytokines , especially il-6 , and proteins under acute conditions is associated with a reduction in mobility as well as a reduced capacity to perform daily activities , the development of fragility syndrome , and increased mortality rates [ 9698 ] . in older men and women , higher levels of il-6 and crp were associated with a two- to three - fold greater risk of losing more than 40% of grip strength over 3 years .
in contrast , there were no longitudinal associations between inflammatory markers and changes in grip strength among high functioning elderly participants from the macarthur study of successful aging .
more recently , hamer and molloy   demonstrated , in a large representative community - based cohort of older adults ( 1,926 men and 2,260 women ( aged 65.3  9.0 years ) ) , that crp was associated with poorer hand grip strength and chair stand performance in women but only chair stand performance in men .
in addition , haddad et al .   demonstrated atrophy in the tibialis anterior muscle of mice following the injection of relatively low doses of il-6 . in a recent randomized trial that employed aerobic and strength training in a group of elderly participants , significant reductions in various inflammatory markers
( il-6 , crp , and il-18 ) were observed for aerobic but not strength training .
in contrast , combined resistance and aerobic training that increased strength by 38% resulted in significant reductions in crp .   
myostatin was first discovered during screening for novel members of the transforming growth factor- superfamily and shown to be a potent negative regulator of muscle growth .
mutations in myostatin can lead to massive hypertrophy and/or hyperplasia in developing animals , as evidenced by knockout experiments in mice .
myostatin levels increase with muscle atrophy due to unloading in mice and humans [ 106 , 107 ] and with severe muscle wasting in hiv patients .
administration of myostatin in vivo to adult mice induces profound muscle loss analogous to that seen in human cachexia syndromes .
.    many researchers have conducted experiments to inhibit myostatin in models of muscle disorders such as duchenne muscular dystrophy , als , and cancer cachexia .
in addition , several investigators examined the effect of inhibiting myostatin to counteract sarcopenia using animals [ 110 , 111 ] .
more recently , murphy et al .   showed , by way of one - weekly injections , that a lower dose of pf-354 ( 10  mg / kg ) significantly increased the fiber cross - sectional area ( by 12% ) and in situ muscle force ( by 35% ) of aged mice .  
skeletal muscle is the primary site of insulin - mediated glucose disposal , the largest reservoir of glycogen in the human body , and a key determinant of energy expenditure .
hence , several recent studies have also investigated the effects of genetic and pharmacological inhibition of myostatin , and the resultant resistance - trained phenotype , on the prevention and treatment of obesity and type 2 diabetes mellitus [ 112 , 113 ] . similar to these results , zhang et al .   demonstrated that the inhibition of myostatin increased skeletal muscle mass and reduced body weight , fat mass , and circulating concentrations of triacylglycerol caused by a high - fat diet
postnatal blockade of myostatin with a neutralizing antibody in obese insulin - resistant mice significantly improved glucose homeostasis , lowered circulating triacylglycerols , and increased circulating concentrations of the adipose tissue - derived cytokine and adiponectin [ 115 , 116 ] .
these findings highlight the therapeutic potential of antibody - directed myostatin inhibition for sarcopenic obesity .
although many researchers expect myostatin levels to be increased not only in muscle but also in serum , blood myostatin levels have not been shown to increase with age .  
adipose tissue itself generates a myriad of hormones and other bioactive proteins , including leptin ( in normal concentrations induces satiety and regulates body composition ) and adiponectin ( anti - inflammatory and antiatherogenic ) .
structurally , adiponectin contains a carboxyl - terminal globular domain and an amino - terminal collagenous domain and also shares extensive sequence homology with collagen viii and x .
adiponectin circulates in serum as a range of multimers from low - molecular weight trimers to high - molecular weight dodecamers . with the exception of severe cases of undernutrition   and in the newborn ,
there is a strong negative correlation between plasma adiponectin concentrations in humans and fat mass , with obesity reducing adiponectin levels and weight reduction increasing them [ 45 , 123 ] .   
adiponectin has been shown to improve a whole - body insulin sensitivity in models of genetic and diet - induced obesity [ 124 , 125 ] .
adiponectin stimulates fatty acid oxidation and glucose uptake in skeletal muscle   and adipose tissue , effects which are dependent on amp - activated protein kinase ( ampk ) signaling .
a study in human skeletal muscle   and in primary myotubes   suggested that skeletal muscle contains abundant levels of both adipor1 and adipor2 but that liver primarily expresses adipor2 .
adiponectin 's activation of ampk signaling is blunted in obesity , despite similar adipor1 and adipor2 expression .
adiponectin activates ampk and inhibits nf-b signaling , decreasing monocyte , macrophage , and dendritic cell production of tnf- and interferon ( ifn)- while increasing the production of anti - inflammatory cytokines , il-10 , and il-1r .
adiponectin directly inhibits natural killer ( nk ) cells by preventing il-2-stimulated cytotoxicity and ifn- production .  
leptin acts mainly through the central nervous system , binding to specific hypothalamic receptors and regulating appetite , neuroendocrine pathways , and the autonomic nerves which bring about effects on peripheral tissues .
nevertheless , leptin receptor expression has been reported to occur in pancreatic -cells , muscle , liver , and fat , among other peripheral tissues , suggesting the existence of a direct effect of leptin in addition to its central action . with the exception of fat tissue [ 136 , 137 ] , in vivo treatment with leptin
, chronic peripheral leptin administration induces an increase of glucose uptake under euglycemic- hyperinsulinemic conditions [ 137 , 138 ] , and the same has been observed after the microinjection of leptin into the ventromedial hypothalamus . in addition , leptin is largely proinflammatory because leptin increases tnf- , il-6 , and il-12 production by monocytes [ 45 , 118 ] .
interestingly , in obese but not in lean rats , leptin administration has been proven to decrease insulin signaling in liver .
since obese rats show central leptin resistance and hyperleptinemia similar to aged rats , it can be speculated that during aging , the direct effects of leptin on peripheral tissues could prevail over its central action and contribute to the development and maintaining of a state of insulin resistance .  
two recent studies showed marked increase in serum il-10 in elderly humans , although an earlier study did not show a significant difference between middle - aged and very old humans .
il-10 is broadly anti - inflammatory , inhibiting antigen presentation and suppressing release of tnf- , il-2 , ifn- , il-4 , and other cytokines .
indeed , mice homozygous for targeted deletion of the il-10 gene had elevated levels of tnf- , il-6 , ifn- , and il-1 in serum particularly at a later age ( between 72 and 90 weeks ) .
in addition , these mice had higher mortality rates when compared to age and sex - matched b6 control mice . on the other hand , il-10 stimulated nk cell proliferation , cytotoxicity , and cytokine secretion in vitro when combined with il-1 .
in murine cytomegalovirus - infected mice , il-10 promoted nk cell cytotoxic granule release but increased nk cell activation - induced cell death . in the elderly cohort , bmi correlated inversely with the percentage of nk cells and correlated directly with the nk cell apoptosis rate .
therefore , serum il-10 levels may regulate the amount of adipose tissue by modulating several inflammatory cytokines and/or recruiting immune cells ( e.g. , nk cells ) .  
il-15 mrna is expressed in many tissues , but il-15 biosynthesis is very complex , and rna levels do not necessarily indicate protein secretion .
importantly , il-15 requires the presence of il-15r for efficient biosynthesis and secretion [ 154 , 155 ] .
il-15 levels are reported to increase transiently immediately following resistance   and aerobic   exercise , suggesting that il-15 is indeed released from muscle tissue . in mice , muscle and serum
a study of aging rats showed that a longevity - promoting regimen of calorie restriction prevented age - related declines in muscle il-15 expression observed in ad libitum - fed rats . in an intriguing brief report involving human subjects , gangemi et al .  
observed significantly elevated serum il-15 levels in centenarians living independently , suggesting high expression of il-15 conferred protection from both frailty and age - related disease .
il-15 inhibits adipocyte differentiation in culture and obese people have low - blood il-15 levels [ 156 , 161 , 162 ] .
il-15-deficient mice become obese despite unaltered food consumption ; il-15 injections reversed both this obesity and diet - induced obesity , lowered glucose levels and increased insulin sensitivity [ 161 , 163 ] .  
figure 1 provides an overview of the action of dysregulated adipokines to various organs ( e.g. , hypothalamus and skeletal muscle ) in sarcopenic obesity .
  adipose tissue infiltration of skeletal muscle increases with age [ 164 , 165 ] .
recent studies have demonstrated that mitochondrial damage occurs in obese individuals due to enhanced ros and chronic inflammation caused by increased fatty acid load .
specifically , in skeletal muscle , the expression of pgc-1 drives not only mitochondrial biogenesis and the establishment of oxidative myofibers but also vascularization .
it was found that a high - fat diet or fatty acid treatment caused a reduction in the expression of pgc-1 and other mitochondrial genes in skeletal muscle .
a recent study has also demonstrated that transgenic overexpression of pgc-1 in skeletal muscle improved sarcopenia and obesity associated with aging in mice .
therefore , the well - known sarcopenia - attenuating effects of endurance training may be attributable to the protection against mitochondrial disorders ( apoptosis , oxidative damage , etc . ) caused by an increase in the production of pgc-1 .  
the american college of sports medicine recommends a multicomponent training exercise programme ( strength , endurance , balance , and flexibility ) to improve and maintain physical function in older adults .
resistance exercise has been investigated as an approach to counteract sarcopenia by stimulating protein synthesis and cause muscle hypertrophy with increased muscle strength and with improved physical performance .
most of the studies had a multicomponent program of 90-min sessions per week , consisting of 15  min of balance training , 15  min of flexibility , 30  min of aerobic exercise , and 30  min of high - intensity resistance training .   to study the impact of each exercise modality in more detail , davidson et al .  
randomized 60- to 80-year - old obese subjects into 4 groups : a control group , a group that had progressive resistance training , a group that performed aerobic exercise , and a group that combined progressive resistance training with aerobic exercise .
after 6 months , body weight decreased by 0.6  kg in the resistance , by 2.8  kg in the aerobic , and by 2.3  kg in the combined exercise group .
abdominal fat and visceral fat decreased and endurance capacity improved significantly in the aerobic and combined exercise group .
skeletal muscle mass and muscle strength increased in the resistance and combined exercise groups only .
insulin resistance improved by 31% in the aerobic group and by 45% in the combined exercise group , whereas it did not change in the resistance training group .
the combination of progressive resistance training and aerobic exercise is the optimal exercise strategy for simultaneous improvement of insulin resistance and functional limitations in the elderly .
diet - induced weight loss results in a decrease in both fat mass and fat - free mass and so could exacerbate the age - related loss of muscle mass and further impair physical function . based on intensive research concerning sarcopenia and sarcopenic obesity , dietary guidelines
were adjusted to prevent sarcopenic obesity and to guide the medical profession in managing weight loss in the presence of sarcopenic obesity [ 173 , 174 ] .   in the treatment of subjects with , or at risk of ,
sarcopenic obesity , the energy deficit should be more moderate than usual ( range of 200750  kcal ) with emphasis on a higher intake of proteins ( up to 1.5  g / kg ) of high biological quality , ensuring adequate renal function . when restricting energy intake , protein intake must be maintained or even increased as dietary protein , and amino acids are the most effective means to slow down or prevent muscle protein catabolism .
it increases muscle protein synthesis by modulating the activation of mammalian target of rapamycin complex 1 and signaling components of translation initiation . in order to optimize the anabolic response to ingested high - quality proteins ,
in contrast to younger people , the elderly have a diminished anabolic response to proteins when they are coingested with carbohydrates .
the population is growing older , and the prevalence of obesity in the elderly is rising . aging and obesity are two conditions that present an important part of health costs .
the impact of sarcopenic obesity on physical , metabolic , and cardiovascular functions is becoming a primary concern amongst nutritionists , geriatricians , and public health officers .
the etiopathogenesis of sarcopenic obesity is complex and multiple factors can interplay , including lifestyle , endocrine , and immunological factors [ 176 , 177 ] . decreased physical activity and energy expenditure with aging predispose to fat accumulation and fat redistribution but muscle loss .
sarcopenic obesity seems to be modulated by an age - related decrease in serum il-15 and adiponectin and/or chronic inflammation ( upregulation of tnf- , il-6 , and myostatin ) .  
lifestyle intervention should be the first step , and its effects have been extensively in the obese elderly .
obesity and specifically sarcopenic obesity , in the elderly , are potentially preventable , and should be tackled from younger ages and also during major later - life transitions such as retirement .
 in normal aging , changes in the body composition occur that result in a shift toward decreased muscle mass and increased fat mass . 
 the loss of muscle mass that occurs with aging is termed sarcopenia and is an important cause of frailty , disability , and loss of independence in older adults . 
 age - related changes in the body composition as well as the increased prevalence of obesity determine a combination of excess weight and reduced muscle mass or strength , recently defined as sarcopenic obesity . 
 weight gain increases total / abdominal fat , which , in turn , elicits inflammation and fatty infiltration in muscle . 
 sarcopenic obesity appears to be linked with the upregulation of tnf- , interleukin ( il)-6 , leptin , and myostatin and the downregulation of adiponectin and il-15 . 
 multiple combined exercise and mild caloric restriction markedly attenuate the symptoms of sarcopenic obesity . 
 intriguingly , the inhibition of myostatin induced by gene manipulation or neutralizing antibody ameliorates sarcopenic obesity via increased skeletal muscle mass and improved glucose homeostasis . in this review , 
 we describe the possible influence of endocrinal changes with age on sarcopenic obesity . 
1. Introduction 
2. Sarcopenic Obesity
3. Endocrinal Adaptation with Age
4. Therapeutic Application
5. Conclusions and Perspectives