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RE: Hirsch C, Anderson ML, Newman A, Kop W, Jackson S, Gottdiener J, et al, for the Cardiovascular Health Study Research Group. The association of race with frailty: The Cardiovascular Health Study. Ann Epidemiol. 2006;16:545-553.
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Skeletal muscle apoptosis, sarcopenia and frailty at old age.
The loss of muscle mass and strength with aging, also referred to as sarcopenia of aging, is a highly prevalent condition among older adults and predicts several adverse outcomes, including disability, institutionalization and mortality. Although the exact mechanisms underlying sarcopenia are far to be unveiled, accumulating preclinical evidence suggests that an age-related acceleration of myocytes loss via apoptosis might represent a key mechanism driving the onset and progression of muscle loss. Furthermore, increased levels of apoptosis have also been reported in old rats undergoing acute muscle atrophy subsequent to muscle unloading, a condition that mimics the muscle loss observed during prolonged bed rest. Notably, preliminary evidence seems to confirm a causative role for apoptosis in age-related muscle loss in human subjects. Several signaling pathways of skeletal muscle apoptosis are currently under intense investigation, with a particular focus on the role played by mitochondria. Here, we will review the most recent evidence regarding various pathways of muscle apoptosis and their modulation by several interventions (caloric restriction, physical exercise, muscle unloading).
Taking musculoskeletal aging out of the bench: do we finally understand frailty?
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Cognitive frailty: Predementia syndrome and vascular risk factors.
With increasing emphasis on early diagnosis of Alzheimer disease (AD), clinical research has focused on the identification of risk factors that may be modified at a preclinical and early clinical stage of dementing disorders. Prevalence and incidence of different predementia syndromes vary as a result of different diagnostic criteria, as well as different sampling and assessment procedures. Particular interest in mild cognitive impairment (MCI) arises from the fact that MCI is thought to be a prodromal phase and therefore highly predictive of subsequent AD. Furthermore, many of the risk factors for cerebrovascular disease (CVD) and vascular dementia (VaD), including serum total cholesterol, hypertension, atherosclerosis, and apolipoprotein E (APOE) genotype have also been shown to increase the risk of AD. Both vascular factors and APOE epsilon4 allele have been associated with higher risk of AD. Some recent studies suggested further that CVD or vascular factors increased the risk of conversion of MCI to dementia. This review will focus on the possible role of vascular risk factors in modulating the risk of age-related cognitive decline, and the progression of predementia syndrome such as MCI to dementia.
Synaptic frailty and clathrin-mediated synaptic vesicle trafficking in Alzheimer's disease.
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Health-care system frailties and public health control of communicable disease on the European Union's new eastern border.
In May, 2004, the border of the European Union (EU) will shift eastward such that the new frontier will be made up by Ukraine, Belarus, and a considerably longer Russian border. Here, we discuss three issues: first, the factors that have contributed to the growth of communicable disease in Russia, Ukraine, and Belarus; second, how public health systems have responded to these challenges; and third, the implications for the EU as a whole. Since the break-up of the Soviet Union, Russia, Ukraine, and Belarus have witnessed substantial political, social, and economic changes. These events have been reflected in changes in the epidemiology of communicable diseases, including tuberculosis and HIV (ie, HIV-1). Moreover, public health systems, rooted in Soviet traditions, are struggling to respond effectively to the challenges of resurgent infectious diseases, such as tuberculosis, and newly emergent challenges such as HIV. The changing patterns of communicable diseases east of the EU's new border has implications for how the EU aids the strengthening of public health systems east of the new frontier. Transborder spread of communicable diseases also challenges communicable disease control systems within the EU. Concerted action is needed by member states and the EU, building on models of cooperation between institutions that have been successful in areas beyond health, if public health systems are to meet the emerging challenges to communicable disease control.
Frailty in elderly Japanese.
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Frailty selection and HIV.
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A brief clinical instrument to classify frailty in elderly people.
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The frailty hypothesis revisited: mainly weak children die of measles.
It has been suggested that measles infection mainly kills frail children who are likely to die anyhow of other infections. If that were true, the proportion of frail children should increase after the introduction of measles vaccination and post-measles mortality compared with mortality in uninfected children should increase when the case fatality declines and frail children are no longer dying of measles. The latter deduction was investigated in Niakhar, Senegal, where the measles case fatality has declined markedly. Measles has been studied in Niakhar during 12 years from 1983 to 1994. We compared long-term mortality after measles infection in periods with both high and low case fatality. The acute measles case fatality rate (CFR) declined from 6.5% in 1983-1986 to 1.5% in 1987-1994, an age-adjusted decline of 66% (RR=0.34 (0.19-0.58)). Between 1983-1986 and 1987-1994, mortality in the first year after measles infection declined by 35% (RR=0.65 (0.37-1.16)), the pattern being the same in the second and third year after infection (RR=0.63 (0.33-1.21)). This reduction could not be related to introduction of immunization, treatment of measles with Vitamin A, or prophylactic use of antibiotics. Controlling for age, immunization, and season, the decline in post-measles mortality was similar to the fall in non-measles-related mortality between the two periods (mortality rate ratio=0.72 (0.64-0.80)). Since the mortality decline in survivors of measles was as large as the decline in mortality among uninfected children, reduction in acute measles mortality did not lead to accumulation of frail children. We doubt measles infection ever eliminated mainly weak children; it always killed a broad spectrum of children, most of whom were "fit to survive". Hence, it seems unlikely that measles vaccination has contributed to the survival of more frail children.
An allele of HRAS1 3'variable number of tandem repeats is a frailty allele: implication for an evolutionarily-conserved pathway involved in longevity.
The human HRAS1 belongs to an evolutionarily-conserved family of genes which enrolls among its members the yeast RAS2, a gene which regulates stress response and longevity in the Saccharomyces cerevisiae. In this paper we report that the frequency of the a3 allele of HRAS1 3'variable number tandem repeat (HRAS1 3'VNTR) decreases in centenarians in respect to young people, and we estimate that during aging a3 carriers have a relative mortality risk of 1.126 (95% CI=1.044-1.213). We propose that the germ-line variability at the HRAS1 locus impacts on the individual's capacity to reach the extreme limits of human life-span. Furthermore, we provide suggestive evidence that a3 HRAS1 3'VNTR allele and inherited variants of the mitochondrial genome (mtDNA haplogroups) do not affect independently human longevity, thus recalling the nucleus-mitochondrion interaction which regulates stress response and life-span in the yeast.
Nuclear chiefs scotch story on frailty of ageing warheads.
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Screening for frailty among seniors in clinical practice.
The normal course of aging is associated with gradual declines in a number of functional abilities. Patients who are at high risk of functional decline are described as frail or vulnerable. A screening tool to identify such patients is needed, as it has been shown that intervention can delay the onset and/or slow the progression of functional decline. This Review describes the methods currently available for nonspecialist evaluation of aging individuals, including behavioral, interview and questionnaire assessments. Such assessments can be undertaken during routine physician visits. In recognition of the time pressures on physicians, this article focuses on those measurements that are fairly comprehensive yet concise, easy to administer in an office setting, and available in English.
Depressed albumin and high-density lipoprotein cholesterol: signposts along the final common pathway of frailty.
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A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS).
OBJECTIVES: To determine the effectiveness of vitamin D and home-based quadriceps resistance exercise on reducing falls and improving the physical health of frail older people after hospital discharge. DESIGN: Multicenter, randomized, controlled trial with a factorial design. SETTING: Five hospitals in Auckland, New Zealand, and Sydney, Australia. PARTICIPANTS: Two hundred forty-three frail older people. INTERVENTIONS: Patients were randomized to receive a single dose of vitamin D (calciferol, 300,000 IU) or placebo tablets and 10 weeks of high-intensity home-based quadriceps resistance exercise or frequency-matched visits. MEASUREMENTS: The primary endpoints were physical health according to the short-form health survey at 3 months and falls over 6 months. Physical performance and self-rated function were secondary endpoints. Assessments took place in the participants' homes at 3 and 6 months after randomization and were performed by blinded assessors. RESULTS: There was no effect of either intervention on physical health or falls, but patients in the exercise group were at increased risk of musculoskeletal injury (risk ratio = 3.6, 95% confidence interval = 1.5-8.0). Vitamin D supplementation did not improve physical performance, even in those who were vitamin D deficient (<12 ng/mL) at baseline. CONCLUSION: Neither vitamin D supplementation nor a home-based program of high-intensity quadriceps resistance exercise improved rehabilitation outcomes in frail older people after hospitalization. There was no effect of vitamin D on physical performance, and the exercises increased the risk of musculoskeletal injury. These findings do not support the routine use of these interventions at these dosages in the rehabilitation of frail older people.