Identification of Novel Genes Involved in Sarcopenia Through RNAi Screening in Caenorhabditis elegansKashyap, Luv; Perera, Subashan; Fisher, Alfred L.
doi: 10.1093/gerona/glr072pmid: 21593014
Background.Aging in humans is characterized by a progressive loss of muscle mass and strength known as sarcopenia. Although considered to be a normal aspect of aging, the loss of strength can have significant effects on the health, functioning, and independence of elderly individuals. Although these aspects of sarcopenia have been well studied, the molecular mechanisms leading to its development are still unclear. The nematode Caenorhabditis elegans might be a novel animal model for sarcopenia as worms experience sarcopenia during aging and mutations affecting the daf-2/insulin-like signaling pathway are able to delay this process.Methods.Via the use of RNA interference, we screened a total of 43 genes, most of which have been shown to be required for the enhanced longevity of daf-2 mutants, to assess for the effects of these genes on muscle function and worm mobility during aging.Results.We identified 17 novel genes that are essential for the delay in the onset of sarcopenia in daf-2 mutants. The identified genes include splicing factors, vacuolar sorting proteins, transcription factors, and metabolic enzymes. Using a transgenic strain that only responds to RNA interference in the body wall muscle, we also found that most of the identified genes act in muscle to prevent the onset of sarcopenia.Conclusions.Our results demonstrate that at least in worms, specific genetic pathways that modify the development of sarcopenia can be identified. Interestingly, almost all the identified genes also have a known human homolog, and hence, our findings may offer significant leads toward the identification of genes involved in sarcopenia in people.
Dynapenia and Aging: An UpdateManini, Todd M.; Clark, Brian C.
doi: 10.1093/gerona/glr010pmid: 21444359
In 2008, we published an article arguing that the age-related loss of muscle strength is only partially explained by the reduction in muscle mass and that other physiologic factors explain muscle weakness in older adults (Clark BC, Manini TM. Sarcopenia / dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63:829834). Accordingly, we proposed that these events (strength and mass loss) be defined independently, leaving the term sarcopenia to be used in its original context to describe the age-related loss of muscle mass. We subsequently coined the term dynapenia to describe the age-related loss of muscle strength and power. This article will give an update on both the biological and clinical literature on dynapeniaserving to best synthesize this translational topic. Additionally, we propose a working decision algorithm for defining dynapenia. This algorithm is specific to screening for and defining dynapenia using age, presence or absence of risk factors, a grip strength screening, and if warranted a test for knee extension strength. A definition for a single risk factor such as dynapenia will provide information in building a risk profile for the complex etiology of physical disability. As such, this approach mimics the development of risk profiles for cardiovascular disease that include such factors as hypercholesterolemia, hypertension, hyperglycemia, etc. Because of a lack of data, the working decision algorithm remains to be fully developed and evaluated. However, these efforts are expected to provide a specific understanding of the role that dynapenia plays in the loss of physical function and increased risk for disability among older adults.
Prevalence and Predictors of Anemia in a Population-Based Study of Octogenarians and Centenarians in GeorgiaHaslam, Alyson; Hausman, Dorothy B.; Johnson, Mary Ann; Davey, Adam; Poon, Leonard W.; Allen, Robert H.; Stabler, Sally P.
doi: 10.1093/gerona/glr151pmid: 21896502
Background.Anemia has been associated with increased physical and financial costs and occurs more frequently in older individuals. Therefore, the primary objectives of this study were to examine the prevalence and possible predictors of anemia in the very old.Methods.Hemoglobin was used to identify those with anemia in a group of centenarians and near centenarians (98, n 185) and octogenarians (n 69), who were recruited as part of the population-based multidisciplinary Georgia Centenarian Study. Blood markers, including ferritin, vitamin B12, red blood cell folate, methylmalonic acid, creatinine, and C-reactive protein, demographic variables, and medication and/or supplement usage were used to determine possible predictors of anemia.Results.The prevalence of anemia was 26.2% in octogenarians and 52.1% in centenarians. Low serum albumin (<3.6 g/dL) and decreased estimated glomerular filtration rate (<45 mL/min/m2) were predictors of anemia in centenarians.Conclusions.Anemia is a major health issue, particularly as people age. Because of the high prevalence of anemia in older individuals, awareness of the predictors associated with anemia becomes increasingly important so as to reduce the negative consequences associated with it and allow for the identification of steps that can be taken to correct anemia, including managing chronic disease.
Usefulness of Preclinical Models for Assessing the Efficacy of Late-Life Interventions for SarcopeniaCarter, Christy S.; Marzetti, Emanuele; Leeuwenburgh, Christiaan; Manini, Todd; Foster, Thomas C.; Groban, Leanne; Scarpace, Philip J.; Morgan, Drake
doi: 10.1093/gerona/glr042pmid: 21636833
Caloric restriction and physical exercise have proven beneficial against age-associated changes in body composition and declining physical performance; however, little is known regarding what benefit these interventions might have when initiated late in life. The study of mimetics of diet and exercise and the combination thereof may provide additional treatments for a vulnerable elderly population; however, how and when to initiate such interventions requires consideration in developing the most safe and efficacious treatment strategies. In this review, we focus on preclinical late-life intervention studies, which assess the relationship between physical function, sarcopenia, and body composition. We provide a conceptual framework for the ever-changing definition of sarcopenia and a rationale for the use of an appropriate rodent model of this condition. We finish by providing our perspective regarding the implications of this body of work and future areas of research that may also contribute to the ultimate goal of extending healthspan.
Glucose and Insulin Measurements From the Oral Glucose Tolerance Test and Relationship to Muscle MassKalyani, Rita R.; Metter, E. Jeffrey; Ramachandran, Ramona; Chia, Chee W.; Saudek, Christopher D.; Ferrucci, Luigi
doi: 10.1093/gerona/glr022pmid: 21350243
Background.Diabetes is associated with decreased muscle mass. The effect of higher levels of glucose and insulin on muscle mass has not been studied in individuals without diabetes. We sought to determine the relationship of insulin and glucose measurements from the oral glucose tolerance test (OGTT) with muscle mass in persons without diabetes.Methods.We analyzed data from 587 participants in the Baltimore Longitudinal Study of Aging (mean age 67.3 years, range 2695 years) without diabetes who underwent a 2-hour OGTT, including glucose and insulin measurements taken every 20 minutes and assessment of midthigh muscle cross-sectional area by computed tomography, taken as a proxy measure of muscle mass. Linear regression models and Bayesian model averaging were used to explore the independent cross-sectional association of various OGTT-derived measures and midthigh muscle cross-sectional area, independent of confounders.Results.Individually, fasting glucose, fasting insulin, OGTT glucose (40, 60, 80, 100, and 120 minutes), OGTT insulin (20, 60, 80, 100, and 120 minutes), homeostasis model assessment of insulin resistance, integrated glucose area, and integrated insulin area were inversely associated, and the Matsuda index was positively associated, with the midthigh muscle cross-sectional area (standardized to body weight) after adjustment for age, sex, race, height, physical activity, and peroneal motor nerve conduction velocity (all ps <.05). When considered together, the Matsuda index and fasting glucose were the strongest predictors of lower midthigh muscle cross-sectional area after covariate adjustment.Conclusions.Higher fasting and OGTT values of both glucose and insulin are associated with lower muscle mass. Longitudinal studies are needed to verify whether individuals free of diabetes that have higher glucose and insulin during an OGTT are at risk for accelerated muscle mass decline with aging.
Neuromuscular Contributions to Age-Related WeaknessClark, David J.; Fielding, Roger A.
doi: 10.1093/gerona/glr041pmid: 21415261
Background.Declines in skeletal muscle mass and quality are important factors contributing to age-related weakness. Neural activation of agonist and antagonist muscles may also be important contributing factors.Methods.We conducted a review of the scientific literature on older adults to determine (a) methodologies used to quantify activation, (b) the potential role of agonist and antagonist activation on weakness, and (c) some possible neurophysiological mechanisms that may underlie impaired activation.Results.The cumulative evidence indicates that agonist activation is impaired in some, but not all, older adults and that this impairment contributes to age-related weakness. It is possible that antagonist coactivation also plays a role in age-related weakness, though a definitive link has not been established.Conclusion.Future research should focus on improving quantitative measurement and mechanistic understanding of impaired activation with aging.