Persistent, sub-clinical inflammation, as indicated by higher circulating levels of inflammatory mediators, is a prominent risk factor for several chronic diseases, as well as aging-related disability. As such, the inflammatory pathway is a potential therapeutic target for lifestyle interventions designed to reduce disease and disability. Physical exercise is well recognized as an important strategy for reducing the risk of chronic disease, and recent research has focused on its role in the improvement of the inflammatory profile. This review summarizes the evidence for and against the role of increasing physical activity in the reduction of chronic inflammation. Large population-based cohort studies consistently show an inverse association between markers of systemic inflammation and physical activity or fitness status, and data from several small-scale intervention studies support that exercise training diminishes inflammation. However, data from large, randomized, controlled trials designed to definitively test the effects of exercise training on inflammation are limited, and results are inconclusive. Future studies are needed to refine our understanding of the effects of exercise training on systemic low-grade inflammation, the magnitude of such an effect, and the amount of exercise necessary to elicit clinically meaningful changes in the deleterious association between inflammation and disease.
inflammation; exercise; cytokines; acute phase proteins; physical activity
Aging results in chronic low grade inflammation that is associated with increased risk for disease, poor physical functioning and mortality. Strategies that reduce age-related inflammation may improve the quality of life in older adults. Regular exercise is recommended for older people for a variety of reasons including increasing muscle mass and reducing risk for chronic diseases of the heart and metabolic systems. Only recently has exercise been examined in the context of inflammation. This review will highlight key randomized clinical trial evidence regarding the influence of exercise training on inflammatory biomarkers in the elderly. Potential mechanisms will be presented that might explain why exercise may exert an anti-inflammatory effect.
Aging; Exercise, Inflammation; Adipose; Elderly
Purpose of review
This review article focuses on the changes that occur in muscle with age, specifically the involuntary loss of muscle mass, strength and function, termed sarcopenia. Particular emphasis is given to the metabolic alterations that characterize sarcopenia, and to the potentially treatable causes of this condition, including age-related endocrine and nutritional changes, and inactivity.
Recent data reported include those regarding the potential role of insulin resistance in the development of sarcopenia, the potential role of androgens and growth hormone in the treatment of this condition, the usefulness of exercise including both resistance and aerobic training to improve muscle growth and function, and, finally, the possible use of nutritional manipulations to improve muscle mass.
Sarcopenia is likely a multifactorial condition that impairs physical function and predisposes to disability. It may be prevented or treated with lifestyle interventions and pharmacological treatment. Further long-term investigations are needed, however, to ascertain what type and combinations of interventions are the most efficacious in improving muscle mass and function in older people.
aging; muscle; sarcopenia; nutrition; exercise; hormones; metabolism
There is pressing need to understand the aging process to better cope with its associated physical and societal costs. The age-related muscle wasting known as sarcopenia is a major contributor to the problems faced by the elderly. By hindering mobility and reducing strength, it greatly diminishes independence and quality of life. In studying the factors that contribute to the development of sarcopenia, the focus is shifting to the study of disordered muscle anabolism. The abnormal response of muscle to previously well-established anabolic stimuli is known as anabolic resistance, and may be a key factor in the development and progression of sarcopenia. Factors such as age, obesity, inflammation, and lipotoxicity contribute to anabolic resistance, and have been studied either directly or indirectly in cell systems and whole animals. Understanding the physiologic and mechanistic basis of anabolic resistance could be the key to formulating new and targeted interventions that would ease the burden currently borne by the world’s aged population.
Sarcopenia; Anabolic resistance; Skeletal muscle
Sarcopenia is the progressive generalized loss of skeletal muscle mass, strength, and function which occurs as a consequence of aging. With a growing older population, there has been great interest in developing approaches to counteract the effects of sarcopenia, and thereby reduce the age-related decline and disability. This paper reviews (1) the mechanisms of sarcopenia, (2) the diagnosis of sarcopenia, and (3) the potential interventions for sarcopenia. Multiple factors appear to be involved in the development of sarcopenia including the loss of muscle mass and muscle fibers, increased inflammation, altered hormonal levels, poor nutritional status, and altered renin–angiotensin system. The lack of diagnostic criteria to identify patients with sarcopenia hinders potential management options. To date, pharmacological interventions have shown limited efficacy in counteracting the effects of sarcopenia. Recent evidence has shown benefits with angiotensin-converting enzyme inhibitors; however, further randomized controlled trials are required. Resistance training remains the most effective intervention for sarcopenia; however, older people maybe unable or unwilling to embark on strenuous exercise training programs.
aged; muscle function; sarcopenia
Exercise reduced tolerance and breathlessness are common in the elderly and can result in substantial loss in functionality and health related quality of life. Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are common underlying causes, but can be difficult to disentangle due to overlap in symptomatology. In addition, other potential causes such as obesity, anaemia, renal dysfunction and thyroid disorders may be involved.
We aim to assess whether screening of frail elderly with reduced exercise tolerance leads to high detection rates of HF, COPD, or alternative diagnoses, and whether detection of these diseases would result in changes in patient management and increase in both functionality and quality of life.
A cluster randomized diagnostic trial. Primary care practices are randomized to the diagnostic-treatment strategy (screening) or care as usual.
Patient population: Frail (defined as having three or more chronic or vitality threatening diseases and/or receiving five or more drugs chronically during the last year) community-dwelling persons aged 65 years and older selected from the electronic medical files of the participating general practitioners. Those with reduced exercise tolerance or moderate to severe dyspnoea (≥2 score on the Medical Research Counsel dyspnoea scale) are included in the study.
The diagnostic screening in the intervention group includes history taking, physical examination, electrocardiography, spirometry, blood tests, and echocardiography. Subsequently, participants with new diagnoses will be managed according to clinical guidelines. Participants in the control arm receive care as usual. All participants fill out health status and other relevant questionnaires at baseline and after 6 months of follow-up.
This study will generate information on the yield of screening for previously unrecognized HF, COPD and other chronic diseases in frail elderly with reduced exercise tolerance and/or exercise induced dyspnoea. The cluster randomized comparison will reveal whether this yield will result in subsequent improvements in functional health and/or health related quality of life.
Reduced exercise tolerance; Dyspnoea; Breathlessness; Heart failure; COPD; Frail; Elderly; Screening
Physical inactivity leads to the accumulation of visceral fat and, consequently, to the activation of a network of inflammatory pathways which may promote development of insulin resistance, atherosclerosis, neurodegeneration, and tumour growth. These conditions belong to the “diseasome of physical inactivity”. In contrast, the protective effect of regular exercise against diseases associated with chronic inflammation may to some extent be ascribed to an anti-inflammatory effect. The so called “acute exercise threshold”, the complex mixture of several variables involved in exercise, such as type, volume, frequency, and intensity range is capable of inducing positive physiological adaptations and has been specifically addressed in the recent literature. The major concern is related to the level of the threshold: “exercise training shifts from a therapeutic adaptive intervention to one with potential pathological consequences”. Nonetheless, if the mechanical stimulus is too weak to disrupt cellular homeostasis, training adaptations will not occur. Answering these questions could present practical applications, especially during inflammatory diseases associated with detrimental muscle effects and could theoretically constitute a “new” therapeutic approach to treat/improve an inflammatory state. This paper aims to describe specific data from the literature regarding the effects of exercise on inflammatory diseases in order to promote a more sophisticated perspective on the anti-inflammatory effects of exercise.
Sarcopenia, characterized as muscle loss that occurs with aging, is a major health problem in an aging population, due to its implications on mobility, quality of life, and fall risk. Protein supplementation could improve the physical fitness by increasing protein anabolism, and exercise has a documented evidence of positive effect on functional status among the elderly. However, the combined effect of both protein supplementation and exercise has not been investigated among sarcopenic elderly in the Asian population. Thus, this study aimed to determine the effectiveness of exercise intervention and protein supplementation either alone or in combination for 12 weeks, on body composition, functional fitness, and oxidative stress among elderly Malays with sarcopenia. Sixty five sarcopenic elderly Malays aged 60–74 years were assigned to the control group, exercise group (ExG), protein supplementation group (PrG), or the combination of exercise and protein supplementation group. A significant interaction effect between body weight and body mass index (BMI) was observed, with the PrG (−2.1% body weight, −1.8% BMI) showing the highest reductions. Further, there was a decrease in % body fat (−4.5%) and an increase in fat-free mass (kg) (+5.7%) in the ExG after 12 weeks (P < 0.05). The highest increments in lower and upper body strength were observed in the PrG (73.2%) and ExG (47.6%), respectively. In addition, the ExG showed a reduction in superoxide dismutase (SOD) levels, and both interventions did not alter either lipid or protein oxidation. In conclusion, the exercise program was found to improve muscle strength and body composition, while protein supplementation reduced body weight and increased upper body strength, among sarcopenic elderly in Malaysia.
protein supplement; aging population; sarcopenic elderly; Malaysia; Asian
PERSISTENT LOW-GRADE INFLAMMATION, as indicated by higher circulating levels of inflammatory mediators such as C-reactive protein, interleukin-6 and tumour necrosis factor-α, is a strong risk factor for several chronic diseases. There are data indicating that decreasing energy intake and increasing physical activity may be effective therapies for reducing overall inflammation. Evidence is strong that circulating levels of inflammatory markers are elevated with total and abdominal obesity, possibly owing to a higher secretion rate of cytokines by adipose tissue in obese people. Moreover, very-low-energy dietary weight loss reduces both circulating markers of inflammation and adipose-tissue cytokine production. Data from several large population-based cohorts show an inverse association between markers of systemic inflammation and physical activity or fitness status; small-scale intervention studies support that exercise training diminishes inflammation. Dietary weight loss plus exercise is likely more effective than weight reduction alone in reducing inflammation. To date, data from randomized, controlled trails designed to definitively test the effects of weight loss or exercise training, or both, on inflammation are limited. Future studies are required to define the amount of weight loss needed for clinically meaningful reductions of inflammation; in addition, fully powered and controlled studies are necessary to clarify the effect of exercise training on chronic, systemic inflammation.
With increasing age and longevity, the rising number of frail elders with complex and numerous health-related needs demands a coordinated health care delivery system integrating cure, care and welfare. Studies on the effectiveness of such comprehensive chronic care models targeting frail elders show inconclusive results. The CareWell-primary care program is a complex intervention targeting community-dwelling frail elderly people, that aims to prevent functional decline, improve quality of life, and reduce or postpone hospital and nursing home admissions of community dwelling frail elderly.
The CareWell-primary care study includes a (cost-) effectiveness study and a comprehensive process evaluation. In a one-year pragmatic, cluster controlled trial, six general practices are non-randomly recruited to adopt the CareWell-primary care program and six control practices will deliver ‘care as usual’. Each practice includes a random sample of fifty frail elders aged 70 years or above in the cost-effectiveness study. A sample of patients and informal caregivers and all health care professionals participating in the CareWell-primary care program are included in the process evaluation. In the cost-effectiveness study, the primary outcome is the level of functional abilities as measured with the Katz-15 index. Hierarchical mixed-effects regression models / multilevel modeling approach will be used, since the study participants are nested within the general practices. Furthermore, incremental cost-effectiveness ratios will be calculated as costs per QALY gained and as costs weighed against functional abilities. In the process evaluation, mixed methods will be used to provide insight in the implementation degree of the program, patients’ and professionals’ approval of the program, and the barriers and facilitators to implementation.
The CareWell-primary care study will provide new insights into the (cost-) effectiveness, feasibility, and barriers and facilitators for implementation of this complex intervention in primary care.
The CareWell-primary care study is registered in the ClinicalTrials.gov Protocol Registration System: NCT01499797
Frail elderly; Complex intervention; Integrated care; Functional status; Cost-effectiveness; Implementation; Process evaluation; Primary care
Sarcopenia, the age associated loss of skeletal muscle mass and function, has considerable societal consequences for the development of frailty, disability and health care planning. A group of geriatricians and scientists from academia and industry met in Rome, Italy on November 18, 2009 to arrive at a consensus definition of sarcopenia. The current consensus definition was approved unanimously by the meeting participants and is as follows: Sarcopenia is defined as the age-associated loss of skeletal muscle mass and function. The causes of sarcopenia are multi-factorial and can include disuse, altered endocrine function, chronic diseases, inflammation, insulin resistance, and nutritional deficiencies. While cachexia may be a component of sarcopenia, the two conditions are not the same. The diagnosis of sarcopenia should be considered in all older patients who present with observed declines in physical function, strength, or overall health. Sarcopenia should specifically be considered in patients who are bedridden, cannot independently rise from a chair, or who have a measured gait speed less that 1.0 m·s−1. Patients who meet these criteria should further undergo body composition assessment using dual energy x-ray absorptiometry (DXA) with sarcopenia being defined using currently validated definitions. A diagnosis of sarcopenia is consistent with a gait speed of less than 1 m·s−1 and an objectively measured low muscle mass (eg: appendicular mass relative to ht2 that is ≤ 7.23 kg/ m2 in men ≤ 5.67 kg/ m2 in men). Sarcopenia is a highly prevalent condition in older persons that leads to disability, hospitalization and death.
muscle; aging; body composition; function; disability
The prevention and treatment of late-life dysfunction are the goals of most geriatricians and should be the primary target for discovery and development of new medicines for elderly people. However, the development of new medicines for elderly people will face a number of challenges that are not seen for other patient populations. The burdens of multiple chronic diseases, low physiological reserve and polypharmacy must result in new clinical trials in frail older people with a high expectation of safety and efficacy. The etiology of functional limitations in elderly people is complex and often ascribed to conditions that escape the traditional definition of disease. While our society urgently needs new treatments that can reduce the burden of physical decline among older persons, guidelines on how these treatments should be developed and tested are currently lacking, in part because a consensus has not yet been achieved regarding the identifiable target diseases. New potential indications included sarcopaenia, anorexia of ageing, frailty, mobility disability and reduced functional capacity secondary to hospitalization. The challenges to conducting clinical trials in the elderly should not offset the great opportunity for the development of new medicines to prevent or reverse age-associated changes in body composition and poor functional capacity in the elderly.
sarcopaenia; functional capacity; elderly; geriatrics
Disability in Activities of Daily Living (ADL) is an adverse outcome of frailty that places a burden on frail elderly people, care providers and the care system. Knowing which physical frailty indicators predict ADL disability is useful in identifying elderly people who might benefit from an intervention that prevents disability or increases functioning in daily life. The objective of this study was to systematically review the literature on the predictive value of physical frailty indicators on ADL disability in community-dwelling elderly people.
A systematic search was performed in 3 databases (PubMed, CINAHL, EMBASE) from January 1975 until April 2010. Prospective, longitudinal studies that assessed the predictive value of individual physical frailty indicators on ADL disability in community-dwelling elderly people aged 65 years and older were eligible for inclusion. Articles were reviewed by two independent reviewers who also assessed the quality of the included studies.
After initial screening of 3081 titles, 360 abstracts were scrutinized, leaving 64 full text articles for final review. Eventually, 28 studies were included in the review. The methodological quality of these studies was rated by both reviewers on a scale from 0 to 27. All included studies were of high quality with a mean quality score of 22.5 (SD 1.6). Findings indicated that individual physical frailty indicators, such as weight loss, gait speed, grip strength, physical activity, balance, and lower extremity function are predictors of future ADL disability in community-dwelling elderly people.
This review shows that physical frailty indicators can predict ADL disability in community-dwelling elderly people. Slow gait speed and low physical activity/exercise seem to be the most powerful predictors followed by weight loss, lower extremity function, balance, muscle strength, and other indicators. These findings should be interpreted with caution because the data of the different studies could not be pooled due to large variations in operationalization of the indicators and ADL disability across the included studies. Nevertheless, our study suggests that monitoring physical frailty indicators in community-dwelling elderly people might be useful to identify elderly people who could benefit from disability prevention programs.
This paper aims to highlight the importance of exercise in patients with rheumatoid arthritis (RA) and to demonstrate the multitude of beneficial effects that properly designed exercise training has in this population. RA is a chronic, systemic, autoimmune disease characterised by decrements to joint health including joint pain and inflammation, fatigue, increased incidence and progression of cardiovascular disease, and accelerated loss of muscle mass, that is, “rheumatoid cachexia”. These factors contribute to functional limitation, disability, comorbidities, and reduced quality of life. Exercise training for RA patients has been shown to be efficacious in reversing cachexia and substantially improving function without exacerbating disease activity and is likely to reduce cardiovascular risk. Thus, all RA patients should be encouraged to include aerobic and resistance exercise training as part of routine care. Understanding the perceptions of RA patients and health professionals to exercise is key to patients initiating and adhering to effective exercise training.
Low-grade inflammation and oxidative stress underlie chronic osteoarthritis. Although best-practice guidelines for osteoarthritis emphasize self-management including weight control and exercise, the role of lifestyle behavior change to address chronic low-grade inflammation has not been a focus of first-line management. This paper synthesizes the literature that supports the idea in which the Western diet and inactivity are proinflammatory, whereas a plant-based diet and activity are anti-inflammatory, and that low-grade inflammation and oxidative stress underlying osteoarthritis often coexist with lifestyle-related risk factors and conditions. We provide evidence-informed recommendations on how lifestyle behavior change can be integrated into “first-line” osteoarthritis management through teamwork and targeted evidence-based interventions. Healthy living can be exploited to reduce inflammation, oxidative stress, and related pain and disability and improve patients' overall health. This approach aligns with evidence-based best practice and holds the promise of eliminating or reducing chronic low-grade inflammation, attenuating disease progression, reducing weight, maximizing health by minimizing a patient's risk or manifestations of other lifestyle-related conditions hallmarked by chronic low-grade inflammation, and reducing the need for medications and surgery. This approach provides an informed cost effective basis for prevention, potential reversal, and management of signs and symptoms of chronic osteoarthritis and has implications for research paradigms in osteoarthritis.
Chronic gastro-oesophageal reflux disease and excessive body fat are considered principal causes of Barrett's oesophagus (a metaplastic change in the cells lining the oesophagus) and its neoplastic progression, oesophageal adenocarcinoma. Metabolic disturbances including altered levels of obesity-related cytokines, chronic inflammation and insulin resistance have also been associated with oesophageal cancer development, especially in males. Physical activity may have the potential to abrogate metabolic disturbances in males with Barrett's oesophagus and elicit beneficial reductions in body fat and gastro-oesophageal reflux symptoms. Thus, exercise may be an effective intervention in reducing oesophageal adenocarcinoma risk. However, to date this hypothesis remains untested.
The 'Exercise and the Prevention of Oesophageal Cancer Study' will determine whether 24 weeks of exercise training will lead to alterations in risk factors or biomarkers for oesophageal adenocarcinoma in males with Barrett's oesophagus. Our primary outcomes are serum concentrations of leptin, adiponectin, tumour necrosis factor-alpha, C-reactive protein and interleukin-6 as well as insulin resistance. Body composition, gastro-oesophageal reflux disease symptoms, cardiovascular fitness and muscular strength will also be assessed as secondary outcomes.
A randomized controlled trial of 80 overweight or obese, inactive males with Barrett's oesophagus will be conducted in Brisbane, Australia. Participants will be randomized to an intervention arm (60 minutes of moderate-intensity aerobic and resistance training, five days per week) or a control arm (45 minutes of stretching, five days per week) for 24 weeks. Primary and secondary endpoints will be measured at baseline (week 0), midpoint (week 12) and at the end of the intervention (week 24).
Due to the increasing incidence and very high mortality associated with oesophageal adenocarcinoma, interventions effective in preventing the progression of Barrett's oesophagus are urgently needed. We propose that exercise may be successful in reducing oesophageal adenocarcinoma risk. This primary prevention trial will also provide information on whether the protective association between physical activity and cancer is causal.
Purpose of review
The economic burden due to the sequela of sarcopenia (muscle wasting in the elderly) are staggering and rank similarly to the costs associated with osteoporotic fractures. In this article we discuss the societal burden and determinants of the loss of physical function with advancing age, the physiologic mechanisms underlying dynapenia (muscle weakness in the elderly), and provide perspectives on related critical issues to be addressed.
Recent epidemiological findings from longitudinal aging studies suggest that dynapenia is highly associated with both mortality and physical disability even when adjusting for sarcopenia, indicating that sarcopenia may be secondary to the effects of dynapenia. These findings are consistent with the physiologic underpinnings of muscle strength, as recent evidence demonstrates that alterations in muscle quantity, contractile quality and neural activation all collectively contribute to dynapenia.
While muscle mass is essential for regulation of whole body metabolic balance, overall neuromuscular function seems to be a critical factor for maintaining muscle strength and physical independence in the elderly. The relative contribution of physiologic factors contributing to muscle weakness are not fully understood, and further research is needed to better elucidate these mechanisms between muscle groups and across populations.
Aging; atrophy; cachexia; muscle wasting; weakness
Frailty among older people is related to an increased risk of adverse health outcomes such as acute and chronic diseases, disability and mortality. Although many intervention studies for frail older people have been reported, only a few have shown positive effects regarding disability prevention. This article presents the design of a two-arm cluster randomized controlled trial on the effectiveness, cost-effectiveness and feasibility of a primary care intervention that combines the most promising elements of disability prevention in community-dwelling frail older people.
In this study twelve general practitioner practices were randomly allocated to the intervention group (6 practices) or to the control group (6 practices). Three thousand four hundred ninety-eight screening questionnaires including the Groningen Frailty Indicator (GFI) were sent out to identify frail older people. Based on their GFI score (≥5), 360 participants will be included in the study. The intervention will receive an interdisciplinary primary care intervention. After a comprehensive assessment by a practice nurse and additional assessments by other professionals, if needed, an individual action plan will be defined. The action plan is related to a flexible toolbox of interventions, which will be conducted by an interdisciplinary team. Effects of the intervention, both for the frail older people and their informal caregivers, will be measured after 6, 12 and 24 months using postal questionnaires and telephone interviews. Data for the process evaluation and economic evaluation will be gathered continuously over a 24-month period.
The proposed study will provide information about the usefulness of an interdisciplinary primary care intervention. The postal screening procedure was conducted in two cycles between December 2009 and April 2010 and turned out to be a feasible method. The response rate was 79.7%. According to GFI scores 29.3% of the respondents can be considered as frail (GFI ≥ 5). Nearly half of them (48.1%) were willing to participate. The baseline measurements started in January 2010. In February 2010 the first older people were approached by the practice nurse for a comprehensive assessment. Data on the effect, process, and economic evaluation will be available in 2012.
Tropism and efficiency of skeletal muscle depend on the complex balance between anabolic and catabolic factors. This balance gradually deteriorates with aging, leading to an age-related decline in muscle quantity and quality, called sarcopenia: this condition plays a central role in physical and functional impairment in late life. The knowledge of the mechanisms that induce sarcopenia and the ability to prevent or counteract them, therefore, can greatly contribute to the prevention of disability and probably also mortality in the elderly. It is well known that skeletal muscle is the target of numerous hormones, but only in recent years studies have shown a role of skeletal muscle as a secretory organ of cytokines and other peptides, denominated myokines (IL6, IL8, IL15, Brain-derived neurotrophic factor, and leukaemia inhibitory factor), which have autocrine, paracrine, or endocrine actions and are deeply involved in inflammatory processes. Physical inactivity promotes an unbalance between these substances towards a pro-inflammatory status, thus favoring the vicious circle of sarcopenia, accumulation of fat – especially visceral – and development of cardiovascular diseases, type 2 diabetes mellitus, cancer, dementia and depression, according to what has been called “the diseasome of physical inactivity”.
skeletal muscle; sarcopenia; aging; myokine
It has become clear in recent years that periodontitis is an inflammatory disease initiated by oral microbial biofilm. This distinction implies that it is the host response to the biofilm that destroys the periodontium in the pathogenesis of the disease. As our understanding of pathways of inflammation has matured, a better understanding of the molecular basis of resolution of inflammation has emerged. Resolution of inflammation is an active, agonist-mediated, well-orchestrated return of tissue homeostasis. There is an important distinction between anti-inflammation and resolution; anti-inflammation is pharmacologic intervention in inflammatory pathways, whereas resolution is biologic pathways restoring homeostasis. A growing body of research suggests that chronic inflammatory periodontal disease involves a failure of resolution pathways to restore homeostasis. This article reviews the resolution of inflammation in the context of periodontal disease and the potential for the modification of resolution pathways for the prevention and treatment of periodontal diseases. Proof-of-concept studies in the 1980s demonstrated that pharmacologic anti-inflammation prevented and slowed the progression of periodontal diseases in animals and man. However, the side-effect profile of such therapies precluded the use of non-steroidal anti-inflammatory drugs or other enzyme inhibitors or receptor antagonists in periodontal therapy. The isolation and characterization of resolving agonist molecules has opened a new area of research using endogenous lipid mediators of resolution as potential therapeutic agents for the management of inflammatory periodontitis. Work in animal models of periodontitis has revealed the potential of this therapeutic approach for its prevention and treatment and forced the reconsideration of our understanding of the pathogenesis of human periodontal diseases.
Anti-inflammatory; lipoxins; Porphyromonas gingivalis; periodontal disease; resolvin E1
Association between chronic inflammation and cancer development is exemplified by inflammatory bowel disease (IBD) where patients with chronic uncontrolled colitis have a significantly increased risk of developing colitis-associated colorectal cancer (CACC). CACC appears to progresses through the inflammation-dysplasia-carcinoma sequence. This highlights the need to identify targets and interventions that reduce inflammation and prevent development of dysplasia in the context of IBD. Using the dextran sulfate sodium (DSS) mouse model of chronic colitis and CACC, we show that an important target of intervention in human disease would be the epithelial cell molecule MUC1 that is aberrantly expressed on inflamed colonocytes and promotes inflammation and progression to CACC. We show that a MUC1 vaccine can ameliorate chronic colitis and prevent development of dysplasia in the colon and thus extend survival in human MUC1 transgenic mice. This study supports the potential of prophylactic vaccines to target antigens that become aberrantly expressed in chronic inflammation (e.g., IBD) and continue to be expressed on the associated cancers (e.g., colon cancer), to prevent and/or treat both diseases.
Inflammatory Bowel Disease; MUC1; cancer vaccine; colon cancer; inflammation
Sarcopenia, the loss of muscle mass and function with ageing, is a multifactorial condition that slowly develops over decades and becomes a significant contributor to disability in the older population. Malnutrition and alterations in the muscle anabolic response to nutritional stimuli have been identified as potentially preventable factors that may significantly contribute to sarcopenia. In the present article we review the most recent findings regarding the role of nutritional factors in the development, prevention and treatment of sarcopenia. Specifically, we focus on the nutritional needs of the elderly; the age-related changes in the response of muscle protein metabolism to feeding and to the endogenous hormones released during feeding; and the role played by the splanchnic tissues in the response of muscle proteins to feeding. Finally, we review the issues relative to the potential use of nutritional therapies, including supplementation, for the prevention and treatment of sarcopenia.
Ageing; Sarcopenia; Protein metabolism
Inflammatory bowel disease (IBD) is a common and lifelong disabling gastrointestinal disease. Emerging treatments are being developed to target inflammatory cytokines which initiate and perpetuate the immune response. Adenosine is an important modulator of inflammation and its anti-inflammatory effects have been well established in humans as well as in animal models. High extracellular adenosine suppresses and resolves chronic inflammation in IBD models. High extracellular adenosine levels could be achieved by enhanced adenosine absorption and increased de novo synthesis. Increased adenosine concentration leads to activation of the A2a receptor on the cell surface of immune and epithelial cells that would be a potential therapeutic target for chronic intestinal inflammation. Adenosine is transported via concentrative nucleoside transporter and equilibrative nucleoside transporter transporters that are localized in apical and basolateral membranes of intestinal epithelial cells, respectively. Increased extracellular adenosine levels activate the A2a receptor, which would reduce cytokines responsible for chronic inflammation.
Crohn’s disease; Ulcerative colitis; Inflammatory bowel diseases; Epithelial cells; Membrane transporters; Immuno-modulator
The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation in Age-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified.
Sarcopenia, the age-related decline in skeletal muscle mass and function, is a relatively poorly understood process which may play an important role in the incidence of physical disability and falls in older adults. Evidence demonstrates that both genetic and environmental factors contribute to increased susceptibility for sarcopenia development, yet some of these factors may represent unavoidable consequences of ageing.
A review of literature, generally from epidemiological research, was performed to examine the influence that potentially modifiable lifestyle factors (general physical activity, dietary nutrient intake and sun exposure), as well as chronic disease and medication use, may have on sarcopenia progression.
The review demonstrated that while physical activity, nutrient intake and sun exposure often decline during ageing, each may have important but differing benefits for the prevention of muscle mass and functional declines in older adults. Conversely, age-related increases in the prevalence of chronic diseases and the subsequent prescription of pharmacotherapy may exacerbate sarcopenia progression.
The prevalence of poor physical activity, diet and sun exposure, as well as chronic disease and medication use, within older adult populations may be modifiable through simple lifestyle and health care interventions. As such, these factors may represent the most effective targets for sarcopenia prevention during the ageing process.
Sarcopenia; Epidemiology; Physical activity; Diet; Vitamin D; Chronic disease