Sarcopenia, the age-related skeletal muscle decline, is associated with relevant clinical and socioeconomic negative outcomes in older persons. The study of this phenomenon and the development of preventive/therapeutic strategies represent public health priorities. The present document reports the results of a recent meeting of the International Working Group on Sarcopenia (a task force consisting of geriatricians and scientists from academia and industry) held on June 7–8, 2011 in Toulouse (France). The meeting was specifically focused at gaining knowledge on the currently available biomarkers (functional, biological, or imaging-related) that could be utilized in clinical trials of sarcopenia and considered the most reliable and promising to evaluate age-related modifications of skeletal muscle. Specific recommendations about the assessment of aging skeletal muscle in older people and the optimal methodological design of studies on sarcopenia were also discussed and finalized. Although the study of skeletal muscle decline is still in a very preliminary phase, the potential great benefits derived from a better understanding and treatment of this condition should encourage research on sarcopenia. However, the reasonable uncertainties (derived from exploring a novel field and the exponential acceleration of scientific progress) require the adoption of a cautious and comprehensive approach to the subject.

Sarcopenia is an age-related clinical condition characterized by the progressive loss of motor units and wasting of muscle fibers resulting in decreased muscle function. The molecular mechanisms leading to sarcopenia are not completely identified, but the increased oxidative damage occurring in muscle cells during the course of aging represents one of the most accepted underlying pathways. In fact, skeletal muscle is a highly oxygenated tissue and the generation of reactive oxygen species is particularly enhanced in both contracting and at rest conditions. It has been suggested that oral antioxidant supplementation may contribute at reducing indices of oxidative stress both in animal and human models by reinforcing the natural endogenous defenses. Aim of the present paper is to discuss present evidence related to possible benefits of oral antioxidants in the prevention and treatment of sarcopenia.

The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a pro-thrombotic imbalance in the fibrinolysis homeostasis has been hypothesized at the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the resulting of the interactions among multiple plasminogen activators and inhibitors constituing the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen. In this review, current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker which may become a biological parameter to be growingly considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the next future.

Background:

Obesity and a sedentary lifestyle are associated with physical impairments and biologic changes in older adults. Weight loss combined with exercise may reduce inflammation and improve physical functioning in overweight, sedentary, older adults. This study tested whether a weight loss program combined with moderate exercise could improve physical function in obese, older adult women.

Methods:

Participants (N = 34) were generally healthy, obese, older adult women (age range 55–79 years) with mild to moderate physical impairments (ie, functional limitations). Participants were randomly assigned to one of two groups for 24 weeks: (i) weight loss plus exercise (WL+E; n = 17; mean age = 63.7 years [4.5]) or (ii) educational control (n = 17; mean age = 63.7 [6.7]). In the WL+E group, participants attended a group-based weight management session plus three supervised exercise sessions within their community each week. During exercise sessions, participants engaged in brisk walking and lower-body resistance training of moderate intensity. Participants in the educational control group attended monthly health education lectures on topics relevant to older adults. Outcomes were: (i) body weight, (ii) walking speed (assessed by 400-meter walk test), (iii) the Short Physical Performance Battery (SPPB), and (iv) knee extension isokinetic strength.

Results:

Participants randomized to the WL+E group lost significantly more weight than participants in the educational control group (5.95 [0.992] vs 0.23 [0.99] kg; P < 0.01). Additionally, the walking speed of participants in the WL+E group significantly increased compared with that of the control group (reduction in time on the 400-meter walk test = 44 seconds; P < 0.05). Scores on the SPPB improved in both the intervention and educational control groups from pre- to post-test (P < 0.05), with significant differences between groups (P = 0.02). Knee extension strength was maintained in both groups.

Conclusion:

Our findings suggest that a lifestyle-based weight loss program consisting of moderate caloric restriction plus moderate exercise can produce significant weight loss and improve physical function while maintaining muscle strength in obese, older adult women with mild to moderate physical impairments.

Background: the existence of a relationship among inflammation, high-density lipoprotein cholesterol (HDL-C) and physical function has been suggested.

Objective: the aim of the study is to investigate the possible interaction of HDL-C on inflammation and physical function.

Design: cross-sectional study.

Setting: town of Tuscania (Italy).

Subjects: all the 329 community-dwelling older persons aged ≥75 years (mean age 79.8 ± 5.2 years, women 56.2%).

Methods: HDL-C, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and interleukin-6 (IL-6) were measured. Activities of daily living (ADL), instrumental ADL (IADL) and 4-m walking speed were assessed. Linear regression models were performed.

Results: given the multiple significant interactions, models were stratified according to HDL-C concentrations. In participants with normal HDL-C concentrations, only IL-6 showed a significant association with IADL (β = −0.439, SE = 0.176, P = 0.01). In participants with low HDL-C concentrations, all three inflammatory biomarkers were significantly associated with 4-m walking speed and IADL. IL-6 was also significantly associated with ADL (β = −0.755, SE = 0.259, P = 0.006), whereas borderline significances were reported for CRP and ESR.

Conclusions: the association between inflammation and physical function is particularly enhanced in elders with low HDL-C concentrations. Though HDL-C may merely act as a wellbeing index, HDL-C concentrations should be considered in studies evaluating inflammation and physical function.

Objectives

Aim of the present study is to evaluate whether an ACE inhibitor intervention is able to significantly improve physical performance and muscle strength in a sample of older persons.

Design

Double-blind, cross-over, randomized, placebo-controlled trial.

Setting

The Trail of Angiotensin Converting Enzyme Inhibition and Novel Cardiovascular Risk Factors (TRAIN) study.

Participants

Two hundred fiftyseven subjects aged 55 years and older with high cardiovascular risk profile.

Intervention

Six month of fosinopril use versus placebo.

Measurements

The Short Physical Performance Battery score (rescaled to obtain a continuous variable ranging from 0 to 3 points), and the hand grip strength were measured at the baseline visit, and after 6 and 12 months of follow-up. Paired t-test analyses were performed to compare results of physical function measures after ACE inhibition and placebo interventions.

Results

Mean age of the sample population was 65.97 (standard deviation 7.41) years old. No statistically significant difference was found at the Short Physical Performance Battery (p=0.23) and hand grip strength (p=0.57) results after ACE inhibition (2.113, standard deviation [SD] 0.284; and 37.044 kg, SD 12.993 kg, respectively) compared to placebo (2.096, SD 0.298; and 36.898 kg, SD 13.178 kg, respectively). No significant effects from ACE inhibition were also found when the three subtests composing the Short Physical Performance Battery (i.e., 4-meter walking speed, balance, and chair stand tests) were separately analyzed. Consistent negative results were obtained after analyses were restricted to participants showing the highest compliance to treatment and/or receiving the maximum fosinopril dosage.

Conclusion

No significant modifications in physical performance and muscle strength were reported after 6 months of fosinopril use in older persons with high cardiovascular risk profile. Given these negative findings, it is possible that the beneficial effects of ACE inhibitors on physical function might be due to the activation of a virtuous cycle determined by an improved cardiovascular system. Further specifically designed studies are needed to confirm our findings, and expand them to different populations and ACE inhibitors. If our findings will be confirmed, the extra-cardiovascular properties of ACE inhibitors in older persons might be substantially resized.

Background

Sarcopenia, the age-related loss of muscle mass, may not be an isolated process but is associated with an increase in fat mass. The aim of this study was to estimate the mortality risk of sarcopenia in the presence or absence of obesity.

Methods

Data are from 934 participants aged 65 years or older, enrolled in the “Invecchiare in Chianti” study, and followed for 6 years. At baseline, a peripheral quantitative computerized tomography (pQCT) scan was performed on all participants to evaluate the muscle density, and the muscular and fat cross-sectional areas of the calf. Walking speed was measured on a 7-m track. Cox proportional hazard models were performed to estimate the association of pQCT measures (per 1 standard deviation increase) with mortality.

Results

Unadjusted analyses showed significant associations of muscle density (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.69–0.88), muscle area (HR 0.75, 95% CI 0.66–0.86), and fat area (HR 0.82, 95% CI 0.73–0.92) with mortality. After adjustment for potential confounders, no body composition parameter was significantly associated with mortality. Walking speed (used as a reference measure to verify whether the negative results were due to peculiarities of the study sample) confirmed its well-established association with mortality risk (HR 0.73, 95% CI 0.60–0.88). These results did not change after the analyses were stratified according to sarcopenia and body mass index groups, and restricted to participants with frailty or a high inflammatory profile.

Conclusions

Calf skeletal muscle and fat mass are not significant risk factors for mortality in community-dwelling older adults. Walking speed confirmed to be a powerful predictor of health-related events.

Background

Older persons often complain of fatigue, but the functional consequences of this symptom are unclear. The aim of the present study was to evaluate fatigue and its association with measures of physical function and disability in a representative sample of the older population.

Methods

Cross-sectional data from a population-based sample of 1,055 Italian men and women aged 65 and older were analyzed. Fatigue was defined according to two questions evaluating whether participants felt that “everything was an effort” and/or they “could not get going” on three or more days in the past week. Objective measures of physical function were handgrip strength, the Short Physical Performance Battery (SPPB), and 400-m walking speed. Disability was defined as the inability to complete the 400-m walk test and self-reported difficulty in activities of daily living (ADL) and instrumental activities of daily living (IADL).

Results

The prevalence of fatigue was higher in women (29%) than in men (15%). In age-adjusted analyses, fatigued men and women had weaker handgrip strength, lower SPPB score, slower walking speed, and higher mobility, ADL, and IADL disability than nonfatigued persons. Further adjustment for health behaviors, diseases, inflammatory markers, and thyroid function generally reduced the relationship between fatigue and functional outcomes, but fatigue remained significantly associated with SPPB score, walking speed, and mobility and IADL disability.

Conclusions

Older persons who report fatigue had significantly poorer functional status than those who did not report this symptom. The causal link between fatigue and these outcomes should be further investigated.

Objectives

To determine how three different physical performance measures (PPM) combine for added utility in predicting adverse health events in elders.

Design

Prospective cohort study.

Setting

Health, Aging, and Body Composition Study.

Participants

3,024 well-functioning older persons (mean age 73.6 years).

Measurements

Timed gait, repeated chair stands and balance (semi- and full-tandem, and single leg stands each held for 30 seconds) tests were administered at baseline. Usual gait speed was categorized to distinguish high and low risk participants using the previously established 1 m/sec cut-point. The same population-percentile (21.3%) was used to identify cut-points for repeated chair stands (17.05 sec) and balance (53 sec) tests. Cox proportional hazard analyses were performed to evaluate the added value of PPM in predicting mortality, hospitalization, and (severe) mobility limitation events over 6.9 years of follow-up.

Results

Risk estimates for developing adverse health-related events were similarly large for each of the three high risk groups considered separately. A greater number of PPM scores at the high risk level was associated with a greater risk of developing adverse health-related events. When all three PPMs were considered, having only one poor performance was sufficient to indicate a highly significant higher risk of (severe) lower extremity and mortality events.

Conclusion

Although gait speed is considered the most important predictor of adverse health events, these findings demonstrate that poor performance on other tests of lower extremity function are equally prognostic. This suggests that chair stand and standing balance performance may be adequate substitutes when gait speed is unavailable.

Background

Frailty is a common condition in elders and identifies a state of vulnerability for adverse health outcomes.

Objective

Our objective was to provide a biological face validity to the well-established definition of frailty proposed by Fried et al.

Design

Data are from the baseline evaluation of 923 participants aged ≥65 y enrolled in the Invecchiare in Chianti study. Frailty was defined by the presence of ≥3 of the following criteria: weight loss, exhaustion, low walking speed, low hand grip strength, and physical inactivity. Muscle density and the ratios of muscle area and fat area to total calf area were measured by using a peripheral quantitative computerized tomography (pQCT) scan. Analyses of covariance and logistic regressions were performed to evaluate the relations between frailty and pQCT measures.

Results

The mean age (±SD) of the study sample was 74.8 ± 6.8 y, and 81 participants (8.8%) had ≥3 frailty criteria. Participants with no frailty criteria had significantly higher muscle density (71.1 mg/cm3, SE = 0.2) and muscle area (71.2%, SE = 0.4) than did frail participants (69.8 mg/cm3, SE = 0.4; and 68.7%, SE = 1.1, respectively). Fat area was significantly higher in frail participants (22.0%, SE = 0.9) than in participants with no frailty criteria (20.3%, SE = 0.4). Physical inactivity and low walking speed were the frailty criteria that showed the strongest associations with pQCT measures.

Conclusion

Frail subjects, identified by an easy and inexpensive frailty score, have lower muscle density and muscle mass and higher fat mass than do nonfrail persons.

Background and aims

The occiput-wall distance (OWD), a measure of kyphosis, has been associated with postural instability, osteoporosis, disability and depression. The association between OWD and measures of physical performance was evaluated.

Methods

Data from the Invecchiare in Chianti (InCHIANTI) study on home-dwelling people were used. People younger than 65 years and with overt disability at baseline assessment were excluded. The sample population was divided into three groups according to the OWD distribution (1st quartile: short OWD; 2nd and 3rd quartiles: medium OWD; 4th quartile: long OWD). Performance scores were expressed as the percentage of the best performance in this population.

Results

783 persons (55% women) were studied. The mean age for men was 73.8 (SD 6.34) and 75.0 (SD 6.85) for women. In men, a longer OWD was associated with reduced balance and walking speed, but not with impaired performance at the chair standing test. Overall, the association between increased OWD and reduced physical function was weak. In women, OWD was associated with a reduced walking speed, expressed as a percentage of the best performance (mean [SD]: 77% [12], 72% [14], 66% [15] in short, medium and long OWD groups, respectively), and impaired balance (mean [SD]: 97% [11], 95% [13], 90% [21] for short, medium and long OWD groups, respectively).

Conclusions

Our findings suggest that OWD is an easily measurable marker of poor physical function in women. Further research should verify whether OWD predicts incident disability.

Background

Vitamin D status has been hypothesized to play a role in musculoskeletal function. Using data from the InCHIANTI study, we examined the association between vitamin D status and physical performance.

Methods

A representative sample of 976 persons aged 65 years or older at study baseline were included. Physical performance was assessed using a short physical performance battery (SPPB) and handgrip strength. Multiple linear regression was used to examine the association between vitamin D (serum 25OHD), parathyroid hormone (PTH), and physical performance adjusting for sociodemographic variables, behavioral characteristics, body mass index, season, cognition, health conditions, creatinine, hemoglobin, and albumin.

Results

Approximately 28.8% of women and 13.6% of men had vitamin D levels indicative of deficiency (serum 25OHD < 25.0 nmol/L) and 74.9% of women and 51.0% of men had vitamin D levels indicative of vitamin D insufficiency (serum 25OHD < 50.0 nmol/L). Vitamin D levels were significantly associated with SPPB score in men (β coefficient [standard error (SE)]: 0.38 [0.18], p = .04) and handgrip strength in men (2.44 [0.84], p = .004) and women (1.33 [0.53], p =.01). Men and women with serum 25OHD < 25.0 nmol/L had significantly lower SPPB scores whereas those with serum 25OHD < 50 nmol/L had significantly lower handgrip strength than those with serum 25OHD ≥25 and ≥50 nmol/L, respectively (p < .05). PTH was significantly associated with handgrip strength only (p = .01).

Conclusions

Vitamin D status was inversely associated with poor physical performance. Given the high prevalence of vitamin D deficiency in older populations, additional studies examining the association between vitamin D status and physical function are needed.

Background

Physical function measures have been shown to predict negative health-related events in older persons, including mortality. These markers of functioning may interact with the self-rated health (SRH) in the prediction of events. Aim of the present study is to compare the predictive value for mortality of measures of physical function and SRH status, and test their possible interactions.

Methods

Data are from 335 older persons aged ≥ 80 years (mean age 85.6 years) enrolled in the "Invecchiamento e Longevità nel Sirente" (ilSIRENTE) study. The predictive values for mortality of 4-meter walk test, Short Physical Performance Battery (SPPB), hand grip strength, Activities of Daily Living (ADL) scale, Instrumental ADL (IADL) scale, and a SRH scale were compared using proportional hazard models. Kaplan-Meier survival curves for mortality and Receiver Operating Characteristic (ROC) curve analyses were also computed to estimate the predictive value of the independent variables of interest for mortality (alone and in combination).

Results

During the 24-month follow-up (mean 1.8 years), 71 (21.2%) events occurred in the study sample. All the tested variables were able to significantly predict mortality. No significant interaction was reported between physical function measures and SRH. The SPPB score was the strongest predictor of overall mortality after adjustment for potential confounders (per SD increase; HR 0.64; 95%CI 0.48–0.86). A similar predictive value was showed by the SRH (per SD increase; HR 0.76; 95%CI 0.59–0.97). The chair stand test was the SPPB subtask showing the highest prognostic value.

Conclusion

All the tested measures are able to predict mortality with different extents, but strongest results were obtained from the SPPB and the SRH. The chair stand test may be as useful as the complete SPPB in estimating the mortality risk.

Background

Self-assessed health status (SAHS) and physical performance measures (in particular, walking speed) are strong predictors of health-related events. Nevertheless, the possible interaction between them in predicting major outcomes has not been clearly explored.

Objective

The aim of the study is to evaluate the predictive and additive value for mortality of a SAHS measure and a walking speed test.

Methods

Data are from 2,139 Mexican-Americans aged ≥65 years enrolled in the Hispanic Established Populations for Epidemiologic Studies of the Elderly, and followed for 5.8 years. At the baseline visit, participants were asked to answer to the question ‘How is your health in general?’ presented as a four-level Likert item (i.e., poor, fair, good, excellent). They were also asked to ‘walk down and back as fast as it felt safe and comfortable’ along an 8-ft track. Cox proportional hazard models, receiver operating characteristic (ROC) curve, and specificity/sensitivity analyses were performed to evaluate the predictive value of SAHS and walking speed for mortality.

Results

The mean age of the sample was 72.1 years. Participants reporting ‘poor’ SAHS were more likely to die compared to those with ‘excellent’ SAHS, even after adjustment for potential confounders (HR 1.52, 95% CI 1.10–2.10). Similar results were obtained for participants with slow walking speed (<0.29 m/s; HR 1.68, 95% CI 1.27–2.24; reference group: walking speed ≥0.81 m/s). A statistically significant, but weak, correlation between SAHS and walking speed was observed (Pearson's r = 0.069, p = 0.001). No significant differences in areas under curves from ROC analyses were reported for the prediction of mortality when the SAHS and walking speed were tested (alone or in combination). Both tests presented high specificity (≥80%) for the prediction of mortality.

Conclusion

SAHS and walking speed are not only significant and independent predictors of mortality in older Mexican-Americans, but also present a similar predictive value. The additive prognostic value of the two measures is limited.

The free radical theory of aging hypothesizes that oxygen-derived free radicals are responsible for the age-related damage at the cellular and tissue levels. In a normal situation, a balanced-equilibrium exists among oxidants, antioxidants and biomolecules. Excess generation of free radicals may overwhelm natural cellular antioxidant defences leading to oxidation and further contributing to cellular functional impairment. The identification of free radical reactions as promoters of the aging process implies that interventions aimed at limiting or inhibiting them should be able to reduce the rate of formation of aging changes with a consequent reduction of the aging rate and disease pathogenesis. Even if antioxidant supplementation is receiving growing attention and is increasingly adopted in Western countries, supporting evidence is still scarce and equivocal. Major limitations in literature are still needed to be addressed to better evaluate the potential benefits from antioxidant supplementation: 1) an improved understanding of oxidation mechanisms possibly at the basis of the aging process, 2) the determination of reliable markers of oxidative damage and antioxidant status, 3) the identification of a therapeutic window in which an eventual antioxidant supplementation may be beneficial, 4) a deeper knowledge of the antioxidant molecules which in several conditions act as pro-oxidants. In the present paper, after a preliminary introduction to the free radical theory of aging and the rationale of antioxidant supplementation as an anti-aging intervention, we will present an overview of evidence relating antioxidant supplementations with clinical conditions typical of older age (ie, cardiovascular disease, Alzheimer’s disease, cancer). We will also discuss studies that have evaluated whether antioxidant supplementation might improve major outcomes of interest in older persons (ie, physical performance, muscle strength, longevity). Given the large amount of data available on the antioxidant supplementation topic, this overview is not intended to be exhaustive. The aim of this paper is to provide the main basis from which future studies should start and indicate which the main limitations that need to be addressed are.

Aging is commonly defined as the accumulation of diverse deleterious changes occurring in cells and tissues with advancing age that are responsible for the increased risk of disease and death. The major theories of aging are all specific of a particular cause of aging, providing useful and important insights for the understanding of age-related physiological changes. However, a global view of them is needed when debating of a process which is still obscure in some of its aspects. In this context, the search for a single cause of aging has recently been replaced by the view of aging as an extremely complex, multifactorial process. Therefore, the different theories of aging should not be considered as mutually exclusive, but complementary of others in the explanation of some or all the features of the normal aging process. To date, no convincing evidence showing the administration of existing “anti-aging” remedies can slow aging or increase longevity in humans is available. Nevertheless, several studies on animal models have shown that aging rates and life expectancy can be modified. The present review provides an overlook of the most commonly accepted theories of aging, providing current evidence of those interventions aimed at modifying the aging process.