Francisco Jose Tarazona-Santabalbina

Exercise: the lifelong supplement for healthy ageing and slowing down the onset of frailty.

The beneficial effects of exercise have been well recognized for over half a century. Dr Jeremy Morriss pioneering studies in the fifties showed a striking difference in cardiovascular disease between the drivers and conductors on the double‐decker buses in London. These studies sparked off a vast amount of research on the effects of exercise in health, and the general consensus is that exercise contributes to improved outcomes and treatment for several diseases including osteoporosis, diabetes, depression and atherosclerosis. Evidence of the beneficial effects of exercise is reviewed here. One way of highlighting the impact of exercise on disease is to consider it from the perspective of good practice. However, the intensity, duration, frequency (dosage) and counter indications of the exercise should be taken into consideration to individually tailor the exercise programme. An important case of the beneficial effect of exercise is that of ageing. Ageing is characterized by a loss of homeostatic mechanisms, on many occasions leading to the development of frailty, and hence frailty is one of the major geriatric syndromes and exercise is very useful to mitigate, or at least delay, it. Since exercise is so effective in reducing frailty, we would like to propose that exercise be considered as a supplement to other treatments. People all over the world have been taking nutritional supplements in the hopes of improving their health. We would like to think of exercise as a physiological supplement not only for treating diseases, but also for improving healthy ageing.

Biology of frailty: Modulation of ageing genes and its importance to prevent age-associated loss of function

Frailty is associated with loss of functional reserve as well as with the prediction of adverse events in the old population. The traditional criteria of frailty are based on five physical determinations described in the Cardiovascular Health Study. We propose that biological and genetic markers of frailty should be used to increase the predictive capacity of the established clinical indeces. In recent times, research for biological markers of frailty has gained impetus. Finding a biological markers with diagnostic and prognostic capacity would be a major milestone to identify frailty risk, and also pre-frailty status. In the first section of the manuscript, we review the available biomarkers that help to monitor and prevent the evolution and the efficacy of interventions to delay the onset of frailty and to prevent its progression to incapacity. We also discuss the contribution of genetics to frailty. There are scientific bases that support that genetics influences frailty, although environmental factors probably will have the highest contribution. We review the known SNPs of the genes associated with frailty and classify them, taking into account the pathway in which they are involved. We also highlight the importance of longevity genes and their possible relation with frailty, citing centenarians who reach a very old age as an example of successful ageing. Finally, the reversibility of frailty is discussed. It can potentially be treated with nutritional or pharmacological interventions. However, physical exercise seems to be the most effective strategy to treat and prevent frailty. The last section of the manuscript is devoted to explaining the recommendations on the appropriate design of an exercise protocol to maximize its beneficial effects in a population of frail individuals.

A New Frailty Score for Experimental Animals Based on the Clinical Phenotype: Inactivity as a Model of Frailty

The development of animal models to study human frailty is important to test interventions to be translated to the clinical practice. The aim of this work was to develop a score for frailty in experimental animals based in the human frailty phenotype. We also tested the effect of physical inactivity in the development of frailty as determined by our score. Male C57Bl/6J mice, individually caged, were randomly assigned to one of two groups: sedentary (inactive) or spontaneous wheel-runners. We compared the sedentary versus the active lifestyle in terms of frailty by evaluating the clinical criteria used in humans: unintentional weight loss; poor endurance (running time); slowness (running speed); weakness (grip strength), and low activity level (motor coordination) at five different ages: 17, 20, 23, 26 and 28 months of age. Each criterion had a designated cut-off point to identify the mice with the lowest performance. Lifelong spontaneous exercise significantly retards frailty. On the contrary sedentary animals become frail as they age. Thus, physical inactivity is a model of frailty in experimental animals. Our frailty score provides a tool to evaluate interventions in mice prior to translating them to clinical practice.

Exercise training as a drug to treat age associated frailty

Exercise causes an increase in the production of free radicals [1]. As a result of a hormetic mechanism antioxidant enzymes are synthesised and the cells are protected against further oxidative stress. Thus, exercise can be considered as an antioxidant [2]. Age-associated frailty is a major medical and social concern as it can easily lead to dependency. In this review we describe that oxidative stress is associated with frailty and the mechanism by which exercise prevents age-associated frailty. We propose that individually tailored multicomponent exercise programmes are one of the best ways to prevent and to treat age-associated frailty.

A predictive model of the prevalence of delirium in elderly subjects admitted to nursing homes

INTRODUCTION Delirium is common in geriatric patients admitted to nursing homes, with an incidence of 22-79% among long-term residents. AIM To establish a predictive model of the risk of delirium episodes in a sample of elderly people living in nursing homes. MATERIAL AND METHODS A retrospective, cross-sectional case-control study covering a period of 12 consecutive months (April 2014 - March 2015) was carried out. The included cases had suffered at least one episode of delirium during the study period. Sociodemographic and clinical variables as well as risk factors predisposing to or triggering episodes of delirium were recorded. RESULTS A total of 193 cases and 123 controls were recruited. The mean age of the cases was 89.6 years (SD 6.9), and 75.1% were women. The mean age of the controls was 84.7 years (SD 7.42), and 75.6% were women. The prevalence of delirium was 60.7%. The presence of infections (with the exception of urinary tract infections) was the variable offering the best predictive capacity (OR=7.08; 95% CI: 3.30-15.02; p<0.001). Other predictors of delirium were also identified, such as a previous diagnosis of dementia (OR=3.14; 95% CI: 1.81-5.45; p<0.001), the use of anticholinergic drugs (OR=2.98; 95% CI: 1.34-6.60; p=0.007), a diagnosis of depression (OR=1.92; 95% CI: 1.03-3.56; p=0.039), and urinary incontinence (OR=1.73; 95% CI: 0.97-3.08; p=0.065). The area under the curve (AUC) was 0.794 (95% CI: 0.74-0.84; p<0.001). CONCLUSIONS The prevalence of delirium among elderly subjects admitted to nursing homes was 60.7%. Infections (with the exception of urinary tract infections), dementia, anticholinergic drug use, depression and urinary incontinence were predictive of the presence of delirium.