Showing papers in "Journals of Gerontology Series A-biological Sciences and Medical Sciences in 2004"

Untangling the Concepts of Disability, Frailty, and Comorbidity: Implications for Improved Targeting and Care

Abstract: Three terms are commonly used interchangeably to identify vulnerable older adults: comorbidity, or multiple chronicconditions,frailty, anddisability. However, in geriatricmedicine,there isagrowingconsensusthatthese are distinct clinical entities that are causally related. Each, individually, occurs frequently and has high import clinically. This article provides a narrative review of current understanding of the definitions and distinguishing characteristics of each of these conditions,including theirclinical relevance and distinct prevention and therapeutic issues, and how they are related. Review of the current state of published knowledge is supplemented by targeted analysesin selectedareas where no current publisheddataexists. Overall,the goalof this articleis to providea basis fordistinguishingbetweenthesethreeimportantclinicalconditionsinolderadultsandshowinghowuseofseparate, distinct definitions of each can improve our understanding of the problems affecting older patients and lead to development of improved strategies for diagnosis, care, research, and medical education in this area.

Inflammatory Markers and Physical Performance in Older Persons: The InCHIANTI Study

Abstract: Background. Some studies have proposed chronic inflammation as an underlying biological mechanism responsible for physical function decline in elderly people. The aim of this study is to evaluate the relationship between several inflammatory markers and physical performance in an older population. Methods. This study is part of the ‘‘Invecchiare in Chianti’’ (InCHIANTI) study, a prospective population-based study of older people, aimed at identifying risk factors for late-life disability. The study sample consisted of 1020 participants aged 65 years and older living in the Chianti area of Italy. Physical performance was assessed using walking speed, the chair-stand test, and the standing balance test. Hand-grip strength was assessed using a hand-held dynamometer. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor-alpha (TNF-a), IL-10, IL-1b, IL-6sR, and IL1RA were determined. Linear regression analyses were used to assess the multivariate relationship of inflammatory marker levels with physical performance, scored as a continuous variable from 0 to 3, and hand-grip strength after adjustment for demographics, chronic conditions, medication use, and other biological variables. Results. CRP, IL-6, and IL1RA were significantly correlated with physical performance (r ¼� 0.162, r ¼� 0.251, and r ¼� 0.127, respectively). Significant correlations with hand-grip strength were found for CRP and IL-6 (r ¼� 0.081 and r ¼� 0.089, respectively). After adjustment for covariates, high levels of IL-6 and IL-1RA continued to be strongly associated with worse physical performance (p , .001 and p ¼0.004, respectively). High levels of CRP (p , .001) and IL-6 (p , .001) were associated with low hand-grip strength. Mean adjusted physical performance scores ranged from 2.21 in the CRP , 0.59 mg/dl group to 2.07 in the CRP . 0.60 mg/dl group (p for trend ¼.004), and from 2.25 in the lowest IL-6 quartile to 2.08 in the highest IL-6 quartile (p for trend , .001). This trend was also reflected in mean adjusted handgrip strength, with a range from 28.8 kg for the CRP , 0.59 mg/dl group to 26.0 kg for the CRP . 0.60 mg/dl group (p for trend ¼.001), and from 27.4 kg for the lowest IL-6 quartile to 25.1 kg for the highest IL-6 quartile (p for trend ¼.001). Conclusions. Inflammation, measured as high levels of IL-6, CRP, and IL-1RA, is significantly associated with poor physical performance and muscle strength in older persons. These data also support the biological face validity of physical performance measures. The assessment of inflammatory markers may represent a useful screening test and perhaps a potential target of intervention.

Prevalence, Attributes, and Outcomes of Fitness and Frailty in Community-Dwelling Older Adults: Report From the Canadian Study of Health and Aging

Abstract: Background. Frailty and fitness are important attributes of older persons, but population samples of their prevalence, attributes, and outcomes are limited. Methods. The authors report data from the community-dwelling sample (n ¼ 9008) of the Canadian Study of Health and Aging, a representative, 5-year prospective cohort study. Fitness and frailty were determined by self-reported exercise and function level and testing of cognition. Results. Among the community-dwelling elderly population, 171 per 1000 were very fit and 12 per 1000 were very frail. Frailty increased with age, so that by age 85 years and older, 44 per 1000 were very frail. The risk for adverse health outcomes increased markedly with frailty: Compared with older adults who exercise, those who were moderately or severely frail had a relative risk for institutionalization of 8.6 (95% confidence interval, 4.9 to 15.2) and for death of 7.3 (95% confidence interval, 4.7 to 11.4). These risks persist after adjustments for age, sex, comorbid conditions, and poor self-rated health. At all ages, men reported higher levels of exercise and less frailty compared with women. Decreased fitness and increased frailty were also associated with poor self-ratings of health (42% in the most frail vs 7% in the most fit), more comorbid illnesses (6 vs 3), and more social isolation (34% vs 29%). Conclusions. Fitness and frailty form a continuum and predict survival. Exercise influences survival, even in old age. Relative fitness and frailty can be determined quickly in a clinical setting, are potentially useful markers of the risk for adverse health outcomes, and add value to traditional medical assessments that focus on diagnoses.

Predictors of cognitive decline and mortality of aged people over a 10-year period

Abstract: Background. The search for preventable and remediable risk conditions of cognitive decline is ongoing, but results have thus far been inconsistent. According to the hypothesis of our 10-year prospective study, the predictive values of different risk indicators change over time in a general 75þ population. Methods. A population-based sample of 75-, 80-, and 85-year-old individuals (n ¼ 650) underwent comprehensive clinical examinations in 1990 in Helsinki, Finland. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and/or Clinical Dementia Rating (CDR) at baseline and after 1, 5, and 10 years. Results. At baseline, a low MMSE score was associated with age, history of stroke, apolipoprotein E allele e4 (APOE4), and intermittent claudication. After 1 year, cognitive decline was typical of participants suffering from vascular diseases, e.g., heart failure and intermittent claudication. Five-year decline was predicted by the presence of atrial fibrillation (RR [relative risk] 2.8), APOE4 (RR 2.4), elevated C-reactive protein (CRP) (RR 2.3), diabetes mellitus (RR 2.2), and heart failure (RR 1.8). They also tended to increase 5-year all-cause mortality. At 10 years, the decline associated with APOE4 (RR 3.3), slightly elevated serum ionized calcium (RR 3.3), and feelings of loneliness (RR 3.0). Conclusions. Long follow-up of a general aged population explains several inconsistencies of earlier reports. In 75þ individuals, general ill health is a strong associate of cognitive deficits. The strongest predictors of both cognitive decline and mortality are age, APOE4, manifest vascular diseases, and diabetes. The role of new potential predictors, feelings of loneliness and hypercalcemia, needs clinical testing.

Systematic Review of Progressive Resistance Strength Training in Older Adults

Abstract: Background. The aim of this systematic review was to quantify the effectiveness of progressive resistance strength training (PRT) to reduce physical disability in older people. Methods. Randomized controlled trials were identified from searches of relevant databases and study reference lists and contacts with researchers. Two reviewers independently screened the trials for eligibility, rated their quality, and extracted data. Only randomized controlled trials utilizing PRT as the primary intervention in participants, whose group mean age was 60 years or older, were included. Data were pooled using fixed or random effect models to produce weighted mean differences (WMD) and 95% confidence intervals (CI). Standardized mean differences (SMD) were calculated when different units of measurement were used for the outcome of interest. Results. 62 trials (n ¼ 3674) compared PRT with a control group. 14 trials had data available to allow pooling of disability outcomes. Most trials were of poor quality. PRT showed a strong positive effect on strength, although there was significant heterogeneity (41 trials [n ¼1955], SMD 0.68; 95% confidence interval [CI] 0.52, 0.84). A modest effect was found on some measures of functional limitations such as gait speed (14 trials [n ¼ 798], WMD 0.07 meters per second; 95% CI 0.04, 0.09). No evidence of an effect was found for physical disability (10 trials [n ¼ 722], SMD 0.01; 95% CI � 0.14, 0.16). Adverse events were poorly investigated, but occurred in most studies where they were defined and prospectively monitored. Conclusions. PRT results in improvements to muscle strength and some aspects of functional limitation, such as gait speed, in older adults. However, based on current data, the effect of PRT on physical disability remains unclear. Further, due to the poor reporting of adverse events in trials, it is difficult to evaluate the risks associated with PRT.

Old or Frail: What Tells Us More?

Abstract: Background. Selecting elderly persons who need geriatric interventions and making accurate treatment decisions are recurring challenges in geriatrics. Chronological age, although often used, does not seem to be the best selection criterion. Instead, the concept of frailty, which indicates several concurrent losses in resources, can be used. Methods. The predictive values of chronological age and frailty were investigated in a large community sample of persons aged 65 years and older, randomly drawn from the register of six municipalities in the northern regions of the Netherlands (45% of the original addressees). The participants' generative capacity to sustain well-being (i.e., self-management abilities) was used as the main outcome measure. Results. When using chronological age instead of frailty, both too many and too few persons were selected. Furthermore, frailty related more strongly (with beta values ranging from -.25 to -.39) to a decline in the participants' self-management abilities than did chronological age (with beta values ranging from -.06 to -.14). Chronological age added very little to the explained variances of all outcomes once frailty was included. Conclusions. Using frailty as the criterion to select older persons at risk for interventions may be better than selecting persons based only on their chronological age.

Environmental Influences on Cognitive and Brain Plasticity During Aging

Abstract: In the current article, we provide a critical review of the extant literature that has focused on environmental influences on cognitive and brain plasticity over the adult life span The review includes both human epidemiological, and human and nonhuman cross-sectional and longitudinal research We review a number of factors that have been suggested to reduce age-related cognitive decline including both formal and informal education, leisure pursuits, intellectual engagement, and expertise in different skill domains We also examine the literature on cognitive and physical fitness training We conclude with a discussion of the gaps in the literature and suggestions for future research

The Effects of Multidimensional Home-Based Exercise on Functional Performance in Elderly People

Abstract: BACKGROUND: This study tested the hypothesis that a home-based exercise program would improve functional performance in elderly people. METHODS: We conducted a 6-month, single-blinded, randomized controlled trial. 72 community dwelling men and women (aged >/=70 years) with self-reported and laboratory-based functional impairment were recruited for the study. Participants were randomly assigned to either a home-based progressive strength, balance, and general physical activity intervention or an attention-control group that received home-based nutrition education. Functional performance was measured in the laboratory using the Physical Performance Test (PPT) and the Established Populations for Epidemiologic Studies of the Elderly (EPESE) short physical performance battery. Physiologic capacity was measured by strength (one repetition maximum), dynamic balance (tandem walk), gait speed (2-meter walk), and cardiovascular endurance (6-minute walk). RESULTS: 70 participants (97%) completed the 6-month trial. Compliance with study interventions within each group ranged from 75% in controls to 82% in exercisers. PPT increased by 6.1 +/- 13.4% in exercisers and decreased by 2.8 +/- 13.6% in controls (p =.02). EPESE improved by 26.2 +/- 37.5% in exercisers and decreased by 1.2 +/- 22.1% in controls (p =.001). Dynamic balance improved by 33.8 +/- 14.4% in exercisers versus 11.5 +/- 23.7% in controls (p =.0002). There were no differences between groups in the change in strength, gait speed, or cardiovascular endurance. CONCLUSIONS: Minimally supervised exercise is safe and can improve functional performance in elderly individuals. The improvements in functional performance occurred along with improvements in balance but without a significant change in muscle strength or endurance. Language: en

Is an entertainment robot useful in the care of elderly people with severe dementia

Abstract: Objective An entertainment robot was used as occupational therapy instead of animal-assisted therapy to avoid any danger or injury to the patient and maintain cleanliness. This study compared the effectiveness of a robot animal, AIBO, with a toy. Method AIBO is made of metal and responds to spoken commands. We demonstrated AIBO to severely demented elderly people living in a geriatric home and observed their reactions. Results The most frequent reactions to AIBO consisted of looking at, communicating with, and caring for AIBO. The patients recognized that AIBO was a robot. However, once we dressed AIBO, the patients perceived AIBO as either a dog or a baby. Nevertheless, the presentation of AIBO resulted in positive outcomes for the severe dementia patients, including increased communication between the patients and AIBO. Conclusion AIBO was clearly an effective rehabilitation tool in the treatment of severely demented patients.

Training-Related Adaptations in Motor Unit Discharge Rate in Young and Older Adults

Abstract: Background. This study evaluated changes in motor unit (MU) firing rates in young and older adults during exercise training. Methods. Vastus lateralis MU discharge rates were measured in 8 young and 7 older adults. Each participant performed isometric knee extension contractions at 10%, 50%, and 100% of maximal voluntary contraction or effort (MVC) on two separate occasions. Participants then completed a 6-week resistance exercise training protocol. Results. Significant increases in maximal force were observed as early as 1 week after the first baseline testing session, and these were accompanied by increases in the MU discharge rate. Exercise training increased maximal voluntary force by 29% and 36% in the young and older adults, respectively. Motor unit discharge rates at 100% of maximal effort were significantly greater in the young (24.7 pps) than in the older adults (17.8 pps). Furthermore, the young adults also exhibited significantly greater discharge rates at 50% MVC, but there were no differences at the 10% force level. Maximal MU discharge rates increased during the 1-week period separating the two initial testing sessions. After the 6-week training period, maximal MU discharge rates were 15% higher for the young adults and 49% higher for the older adults. No changes in discharge rates were observed for either group at 10% or 50% MVC after exercise training. Conclusions. The early increase in maximal MU discharge rate with repeated maximal force assessment may comprise an important neural mechanism mediating early, rapid gains in muscular force capability.

Impact of Muscle Power and Force on Gait Speed in Disabled Older Men and Women

Abstract: Background. The purpose of this study was to explore the relationship between muscle power output at different external resistances and performance of functional tasks. The authors hypothesized that power at 40% skeletal muscle 1 repetition maximum (1RM), in which contraction velocity is high, would explain more of the variability in tasks such as level walking than would peak power or 1RM strength, in which contraction velocity is lower. Methods. Participants were men and women (n ¼ 48; ages 65–91 years) with physical disability as evidenced by 2 or more deficits on the Medical Outcomes Study Short Form physical function subscale or a score of 9 or less on the Established Populations for the Epidemiologic Studies of the Elderly short physical performance battery. Muscle strength (1RM) was measured using a bilateral leg press exercise, and power output was determined by selecting the highest power output from 6 different contraction velocities: 40%, 50%, 60%, 70%, 80%, and 90% 1RM. Functional performance tasks consisted of habitual gait velocity (HGV) and stair climb (SC) and chair rise (CR) performance. Separate linear regression models were fit for each of the 3 dependent variables (SC, CR, HGV) using 1RM strength, power at 70% 1RM, and power at 40% 1RM as independent variables. All models were adjusted for age, body mass, and sex. Results. Lower extremity power at 70% and 40% 1RM demonstrated greater associations with SC and HGV than did 1RM strength, whereas power at 40% 1RM demonstrated similar or stronger associations with all functional tasks compared with 1RM strength. Power at 40% 1RM explained the same or more of the variability in SC (R 2 ¼ .42 [regression coefficient ¼� .169 6 .06] vs .43 [� .206 6 .071]), CR (R 2 ¼ .28 [� .154 6 .057] vs .24 [� .152 þ .070]) and HGV (R 2 ¼ .59 [.214 þ .37] vs .51 [.223 6 .049]) compared with power at 70% 1RM. Power at 40% 1RM explained more of the variability in the lower intensity (HGV) compared with the higher intensity (SC or CR) functions. Conclusions. Power output at 40% of 1RM explained more of the variability in HGV than did power at 70% 1RM, suggesting that measures such as HGV that require a lower percentage of maximal strength to perform might be more sensitive to differences in contraction velocity. Because HGV is highly predictive of subsequent disability, future studies should evaluate the determinants of muscle power output at low external resistances.

Physiological and Functional Responses to Low-Moderate Versus High-Intensity Progressive Resistance Training in Frail Elders

Abstract: Background. The purpose of this efficacy study was to measure the dose–response effect of a free weight-based resistance training program by comparing the effects of two training intensities (low-moderate and high) of the knee extensor (KE) muscles on muscle function, functional limitations, and self-reported disability. Methods. The authors conducted a single-blinded, randomized, placebo-controlled trial. Twenty-two institutionalized elders (mean age, 81.5 years) were assigned to either high-intensity strength training (HI; n = 8), low-moderate intensity strength training (LI; n = 6), or weight-free placebo-control training (PC; n = 8). The HI group trained at 80% of their 1-repetition maximum and the LI group trained at 40%. All groups performed 3 sets of 8 repetitions, 3 times per week for 10 weeks. Outcome measures included KE maximal strength, KE endurance, and functional performance as assessed by 6-minute walking, chair-rising, and stair-climbing tests, and by self-reported disability. Results. KE strength and endurance, stair-climbing power, and chair-rising time improved significantly in the HI and LI groups compared with the PC group. Six-minute walking distance improved significantly in the HI group but not in the LI group compared with the PC group. Changes observed in HI were significantly different from those observed in the LI group for KE strength and endurance and the 6-minute walking test, with a trend in the same direction for chair-rising and stair-climbing. Changes in strength were significantly related to changes in functional outcomes, explaining 37% to 61% of the variance. Conclusions. These results show strong dose–response relationships between resistance training intensity and strength gains, and between strength gains and functional improvements after resistance training. Low-moderate intensity resistance training of the KE muscles may not be sufficiently robust from a physiologic perspective to achieve optimal improvement of functional performance. Supervised HI, free weight-based training for frail elders appears to be as safe as lower intensity training but is more effective physiologically and functionally.

Looking Forward to a General Theory on Population Aging

Abstract: The main theories on population aging based on recent data on human longevity, life expectancy, morbidity changes, disability trends, and mortality decrease are presented and discussed within their own geographic, cultural, socioeconomic, and medical contexts. The complex interactions between all these components do not facilitate trend forecasting of aging population (healthy aging versus disability pandemic). In the context of population aging, four elements were introduced with their implications: 1) an increase in the survival rates of sick persons, which would explain the expansion of morbidity, 2) a control of the progression of chronic diseases, which would explain a subtle equilibrium between the decrease in mortality and the increase in disability, 3) an improvement of the health status and health behaviors of new cohorts of elderly people, which would explain the compression of morbidity, and eventually 4) an emergence of very old and frail populations, which would explain a new expansion of morbidity. Obviously, all these elements coexist today, and future trend scenarios-expansion or compression of disability-depend on their respective weights leading to the need of elaborating "a general theory on population aging." This theory has to be based on a world harmonization of functional decline measurements and a periodic "International Aging Survey" to monitor global aging through a sample of carefully selected countries.

Aging-Induced Shifts From a Reliance on Sensory Input to Muscle Cocontraction During Balanced Standing

Abstract: Background. Peripheral sensation is the most important sensory system in the maintenance of upright posture in all age groups. With aging, visual and somatosensory processing change their prospective contribution to the maintenance of quiet standing, at debated percentages. Aging is associated with a decrease in balance abilities that, in turn, increases the risk of falling. We used force plate data to show that, with aging, while vision plays a significant role in regulating postural stability (PS), the individual’s perception of his/her stability becomes more significant than vision. Moreover, under experimental conditions, electromyography (EMG) of the ankle musculature of elderly people reveals the adoption of a different strategy, a cocontraction strategy, with or without visual input. The aim of this study was to look at two distinct age groups to determine whether or not a shift takes place in the sensory modality typically relied on while maintaining PS during a static, postural-related task. Method. The participants comprised two groups: a ‘‘young’’ (Y) group of 20 people aged 20‐35, and an ‘‘old’’ (O) group of 32 people aged 65‐84. The role of vision was tested with regard to two differently sized bases of support. They were tested during quiet upright standing on a single force plate in wide base and then in narrow base conditions. Surface EMG was recorded from the tibialis anterior, soleus, rectus femoris, and semitendinous muscles. Results. The older group differed from the younger group when performing the task under the narrow base condition. When participants stood naturally, our EMG data indicated that, unlike the Y group, the O group used cocontraction around the ankle in order to deal with changing conditions and sensory inputs. Significant increases were found in the area, length, and mean velocity of body sway in the older group as compared with the younger group. Discussion. The visual contribution to postural stabilization is significantly greater in the younger population than in the elderly population. Across the older group, lack of vision seemed to interfere less with PS; however, the EMG data indicated that, unlike the Y group, the O participants used cocontraction around the ankle in order to deal with changing conditions and sensory inputs. Conclusion. To cope with the deterioration in their sensory input and processing ability, elderly individuals seemed to have developed a strategy of stiffening and freezing their lower legs during upright standing.

The Estimation of Relative Fitness and Frailty in Community-Dwelling Older Adults Using Self-Report Data

Abstract: Background. While on average health declines with age, it also becomes more variable with age. As a consequence of this marked variability, it becomes more important as people age to have a means of summarizing health status, but how precisely to do so remains controversial. We developed one measure of health status, personal biological age, from a frailty index. The index itself is a count of deficits derived, in the first instance, from a clinical database. In our earlier investigations, personal biological age demonstrated a strong relationship with 6-year survival. Here we extend this approach to self-reported data. Methods. This is a secondary analysis of community-dwelling people aged 65 years and older (n = 9008) in the Canadian Study of Health and Aging. The frailty index was calculated from 40 self-reported variables, representing symptoms, attitudes, illnesses, and function. Personal biological age was estimated for each individual as the age corresponding to the mean chronological age for the index value. Individual frailty (and the related construct of fitness) was calculated as the difference between chronological and personal biological age. Results. The frailty index showed, on average, an exponential increase with age at an average rate of 3% per year. Although women, on average, demonstrate more frailty than men of the same chronological age, their survival chances are greater. The frailty index strongly correlated (Pearson r = .992 for women and .955 for men) with survival. Conclusions. A frailty index, based on self-report data, can be used as a tool for capturing heterogeneity in the health status of older adults.

Repeated Chair Stands as a Measure of Lower Limb Strength in Sexagenarian Women

Abstract: Background Despite inadequate empirical validation, sit-to-stand (STS) performance is often used as a proxy measure of lower limb strength among older adults. Furthermore, the relationships between bilateral isokinetic hip, knee, and ankle joint strength and their contributions to STS performances among older adults have not been established. The authors evaluated these relationships on 2 STS tests (5-chair STS test and 30-second chair STS test) in sexagenarian women. Methods 47 women (mean age, 64.50 years) performed both STS tests on the same day and bilateral isokinetic (60 degrees/second) hip extensor, hip flexor, knee extensor, knee flexor, ankle plantar flexor, and ankle dorsiflexor strength testing within 7 days after STS testing. Regression analyses were performed using the average weight-adjusted isokinetic hip, knee, and ankle joint strength scores as the independent variables and both STS test scores as the dependent variables. Results Regression analyses including all 6 leg strength variables explained 48% (p = .0001) and 35% (p = .007) of the variance in 5-chair STS test scores and 30-second chair STS scores, respectively. Ankle plantar flexor, hip flexor, and knee extensor strength were the strongest predictors for both STS tests. Conclusions Although ankle plantar flexor, hip flexor, and knee extensor strength play essential roles in performing the STS movement, most STS variance was unexplained, suggesting that important additional variables are also involved in completing the movement.

Free Radicals: Key to Brain Aging and Heme Oxygenase as a Cellular Response to Oxidative Stress

Abstract: Aging is one of the unique features in all organisms. The impaired functional capacity of many systems characterizes aging. When such impairments occur in the brain, the susceptibility to neurodegenerative diseases amplifies considerably. The free radical theory of aging posits that the functional impairments in brains are due to the attack on critical cellular components by free radicals, reactive oxygen species, and reactive nitrogen species produced during normal metabolism. In this review, we examine this concept based on the parameters of oxidative stress in correlation to aging. The parameters for lipid peroxidation are phospholipid composition, reactive aldehydes, and isoprostanes. The parameters for protein oxidation are protein carbonyl levels, protein 3-nitrotyrosine levels, electron paramagnetic resonance, and oxidative stress-sensitive enzyme activities. We conclude that free radicals are, at least partially, responsible for the functional impairment in aged brains. The aging brain, under oxidative stress, responds by induction of various protective genes, among which is heme oxygenase. The products of the reaction catalyzed by heme oxygenase, carbon monoxide, iron, and biliverdin (later to bilirubin) each have profound effects on neurons. Although there may be other factors contributing to brain aging, free radicals are involved in the damaging processes associated with brain aging, and cellular stress response genes are induced under free radical oxidative stress. Therefore, this review supports the proposition that free radicals are, indeed, a key to brain aging.

Sex Differences in the Effect of Dietary Restriction on Life Span and Mortality Rates in Female and Male Drosophila Melanogaster

Abstract: Dietary restriction (DR) has been shown to increase life span in taxonomically diverse animal species. In this study we tested for sex differences in the response of life span to graded severity of DR in Drosophila melanogaster. In both sexes, life span peaked at an intermediate food concentration and declined on either side. However, the magnitude of the response and the food concentration that minimized adult mortality differed significantly between the sexes. Female life span peaked at a food concentration 60% of the standard laboratory diet compared to a concentration of 40% for males. Moreover, female flies subject to DR lived up to 60% longer than did starved or fully fed females, whereas males subjected to DR lived only up to 30% longer. Analysis of age-specific mortality rates showed that DR extended life span by decreasing baseline mortality rates in both sexes, and to a greater extent in females. The differences in the response to DR in female and male Drosophila may be due to previously documented sex differences in sensitivity of life span to insulin/insulin-like growth factor-1 signalling or in nutrient/energy demand and allocation/utilization.

Hemoglobin Levels and Skeletal Muscle: Results From the InCHIANTI Study

Abstract: Background. Anemia is associated with reduced physical performance and muscle strength. The aim of the study was to explore whether anemia and hemoglobin levels are associated with differences in quantitative and qualitative measures of muscle and fat. Methods. The study sample consisted of 909 participants 65 years and older enrolled in the ‘‘Invecchiare in Chianti’’ (InCHIANTI) study, a prospective population-based study of older people aimed at identifying risk factors for late-life disability. All the analyses were performed considering continuous hemoglobin levels as well as the dichotomous anemia variable (defined according to World Health Organization criteria as hemoglobin ,12 g/dL in women and ,13 g/dL in men). A peripheral quantitative computed tomography (pQCT) scan was performed in all participants to evaluate total, muscular, and fat cross-sectional areas of the calf and relative muscle density. Ankle extension strength was measured using a hand-held dynamometer. Linear regression analyses were used to assess the multivariate relationship of pQCT and skeletal muscle strength measures with hemoglobin levels and anemia after adjustment for demographics, chronic conditions, medication use, and other biological variables. Results. Participants were aged 74.8 6 6.8 years. In our sample, 94 participants (10.3%) were anemic. Hemoglobin levels were significantly associated with muscle density (b ¼ 0.225 [SE, standard error 0.098], p ¼ .02), muscle area/total area ratio (b ¼ 0.778 [SE 0.262], p ¼ .003), fat area/total area ratio (b ¼� 0.869 [SE 0.225]; p , .001). Skeletal muscle strength and muscle density were highly associated with anemia (b ¼� 3.266 [SE 1.173], p ¼ .005 and b ¼� 0.816 [SE 0.374], p ¼ .03, respectively). Results did not change when analyses were rerun in a restricted sample of participants not affected by major medical conditions. Conclusion. The present study shows that hemoglobin levels are associated with the parameters of body composition obtained by pQCT, and that decreases in muscular strength measures occur in the presence of anemia.

Cerebral White Matter Changes and Geriatric Syndromes: Is There a Link?

Abstract: Cerebral white matter lesions (WMLs), also called "leukoaraiosis," are common neuroradiological findings in elderly people. WMLs are often located at periventricular and subcortical areas and manifest as hyperintensities in magnetic resonance imaging. Recent studies suggest that cardiovascular risk factors are associated with the development of WMLs. These lesions are associated with different geriatric syndromes such as falls, executive cognitive impairment, depressive symptoms, and urinary incontinence. Damage to associative pathways in frontal and subcortical regions due to hypoperfusion may disrupt frontal executive, motor control, and other systems, resulting in these manifestations. WMLs are associated with substantial disability and should not be considered a benign and silent condition as once believed. Interventions addressing cardiovascular risk factors should be undertaken in early or mid-life in order to prevent late-life functional impairment associated with WMLs. After these lesions develop and impair executive cognitive functions, the patient's ability to comply with a complex risk reduction program may be significantly compromised.

Lifestyle, Nutritional Status, Health, and Mortality in Elderly People Across Europe: A Review of the Longitudinal Results of the SENECA Study

Abstract: This article provides an overview of the longitudinal Survey in Europe on Nutrition and the Elderly: a Concerted Action (SENECA) study, which was designed to assess differences in dietary and lifestyle factors among elderly Europeans, and to identify the factors that contribute to healthy aging. Elderly people from Belgium, Denmark, France, Italy, Portugal, Spain, Switzerland, and The Netherlands participated in the SENECA study. Standardized measurements were conducted at baseline in 1988-1989 and were repeated in 1993 and 1999. Diet, physical activity, and smoking, as well as maintenance of health and survival, were assessed. At baseline, considerable differences in lifestyle factors existed among elderly people. Mealtime patterns as well as dietary intake varied across Europe, and geographical patterns were apparent. Similar results were found for engagement in sport or professional activities. The smoking prevalence among women was generally low. Distinct geographical differences were also observed in percentages of deaths during the SENECA study and in overall survival time. A healthy lifestyle was related to stable self-perceived health, a delay in functional dependence, and mortality. Inactivity and smoking, and to a lesser extent a low-quality diet, increased mortality risk. A combined effect of multiple unhealthy lifestyle factors was also observed. The SENECA study showed that a healthy lifestyle at older ages is related to a delay in the deterioration of health status and a reduced mortality risk. Improving and maintaining a healthy lifestyle in elderly people across Europe is a great challenge for the European Community.

Biomarkers of aging: From primitive organisms to humans

Abstract: Leading biologists and clinicians interested in aging convened to discuss biomarkers of aging. The goals were to come to a consensus, construct an agenda for future research, and make appropriate recommendations to policy makers and the public-at-large. While there was not total agreement on all issues, they addressed a number of questions, among them whether biomarkers can be identified and used to measure the physiological age of any individual within a population, given emerging information about aging and new technological advances. The hurdles to establishing informative biomarkers include the biological variation between individuals that makes generalizations difficult; the overlapping of aging and disease processes; uncertainty regarding benign versus pathogenic age-related changes; the point at which a process begins to do damage to the organism, and, if so, when does it occur; and when to distinguish critical damage from noncritical damage. Finally, and significantly, it is difficult to obtain funding for this research.

Does Sarcopenia Originate in Early Life? Findings From the Hertfordshire Cohort Study

Abstract: Background. Sarcopenia is defined as the loss of skeletal muscle mass and strength with aging. Recent epidemiological studies have shown that men and women who grew less well in early life have lower muscle strength. Our objective was to investigate the relationship between birth weight, infant growth, and the development of sarcopenia. Methods. We studied 730 men and 673 women, of known birth weight and weight at 1 year, who were born in Hertfordshire, U.K., between 1931 and 1939. Participants completed a health questionnaire, and we measured their height, weight, and grip strength. Standard deviation scores for birth weight, and for infant growth conditional on birth weight, were analyzed in relation to grip strength before and after adjustment for adult size. Results. Grip strength was most strongly associated with birth weight in men (r ¼ 0.19, p , .001) and women (r ¼ 0.16, p , .001). These relationships remained significant after adjustment for adult height and weight. In contrast, the associations with infant growth were weakened after allowing for adult size. Adjustment for age, current social class, physical activity, smoking, and alcohol did not affect these results. Conclusions. Birth weight is associated with sarcopenia in men and women, independently of adult height and weight. The influence of infant growth on long-term muscle strength appears to be mediated through adult size. Sarcopenia may have its origins in early life, and identifying influences operating across the whole life course may yield considerable advances in developing effective interventions.

The consequences of resistance training for movement control in older adults

Abstract: Older adults who undertake resistance training are typically seeking to maintain or increase their muscular strength with the goal of preserving or improving their functional capabilities. The extent to which resistance training adaptations lead to improved performance on tasks of everyday living is not particularly well understood. Indeed, studies examining changes in functional task performance experienced by older adults following periods of resistance training have produced equivocal findings. A clear understanding of the principles governing the transfer of resistance training adaptations is therefore critical in seeking to optimize the prescription of training regimes that have as their aim the maintenance and improvement of functional movement capacities in older adults. The degenerative processes that occur in the aging motor system are likely to influence heavily any adaptations to resistance training and the subsequent transfer to functional task performance. The resulting characteristics of motor behavior, such as the substantial decline in the rate of force development and the decreased steadiness of force production, may entail that specialized resistance training strategies are necessary to maximize the benefits for older adults. In this review, we summarize the alterations in the neuromuscular system that are responsible for the declines in strength, power, and force control, and the subsequent deterioration in the everyday movement capabilities of older adults. We examine the literature concerning the neural adaptations that older adults experience in response to resistance training, and consider the readiness with which these adaptations will improve the functional movement capabilities of older adults.

Cytokine-Related Aging Process

Abstract: CYTOKINES are soluble peptide messengers that are synthesized by lymphocytes (thus, they were originally called lymphokines), neutrophils, macrophages, and neuronal cells. The first experimental evidence that circulating factors could modulate the immune system was published in 1932 (1). It was not, however, until more than 30 years later that peptide mediators of lymphocyte activity were identified (2). Two years later, Gery and colleagues (3) isolated soluble peptide messengers from macrophages, and the concept of cytokines as ‘‘the great communicators’’ between immune and somatic cells in response to inflammation was born. Today, it is recognized that cytokines can be both proinflammatory and antiinflammatory and have a wide range of effects on organ systems throughout the body (Figure 1). Originally, each cytokine was named after the function it was recognized to perform. However, it soon was realized that cytokines produced multiple functions, and, thus, in 1979, a consensus committee decided to rename the cytokines ‘‘interleukins’’ followed by a number (4). Nonetheless, some cytokines have retained other names, for example, tumor necrosis factors (TNFs) (originally cachectins), interferons, and, most recently, the adipocyteproduced cytokines, or adipocytokines, such as adiponectin and leptin. Recently, there has been an increasing awareness that the cytokine response to nonspecific inflammation may be a component of the pathophysiology of frailty, functional decline, and death in older persons (5,6). Some cytokines, such as interleukin-10 (IL-10), are antiinflammatory and oppose the actions of the proinflammatory cytokines. Westendorp has suggested that the balance between proinflammatory and antiinflammatory cytokines favors either a long life or reproductive success (7). Thus, persons with high levels of tumor necrosis factor alpha (TNFa) and low levels of IL-10 will have few children but live a long time. This is the modern version of Thomas Kirkwood’s ‘‘disposable soma’’ theory, which stated that investment in maintenance and repair comes at the expense of investment in reproduction. Tissue destruction or infection leads to a nonspecific acute-phase response. Markers of this nonspecific response are C-reactive protein (CRP) and serum amyloid protein, which increase rapidly (within 6 hours and peak within 48 hours) following an acute-phase stimulus. CRP derived its name from its ability to precipitate the C-polysaccharide of streptococcus pneumoniae (8). Both CRP and serum amyloid protein are members of the pentraxin family (Gk. penta5 five; ragos5 berries). When CRP binds to damaged cell membranes or lipids, it activates the classical complement pathway through C1q. CRP is increased after acute and chronic infection, in arthritic and other inflammatory disorders, tissue necrosis, neoplasia, cardiovascular disease, insulin resistance syndromes, obesity, smoking, stress, atrial fibrillation, oral estrogen intake, smoking, and coffee consumption (9). Liver disease, weight loss, exercise, moderate alcohol intake, and hepatic hydroxymethyl glutaryl coenzyme A (HMGCoA) reductase inhibitors are associated with lower CRP levels. Autoimmune diseases, such as systemic lupus erythematosus, fail to produce a CRP response. Thus, while CRP is a sensitive marker of disease processes, it is notoriously nonspecific. In older persons, CRP has been shown to be a marker of functional decline and mortality (10–13). Because of the nonspecificity of CRP, there has been a search for more specific markers that could explain the pathophysiology of functional deterioration with aging, sarcopenia, and the anorexia of aging (6,14–21). Interleukin-6 (IL-6) was one of the first cytokines to be linked to the aging process, and has been termed the ‘‘geriatric cytokine’’ (22). IL-6 is released from macrophages and T lymphocytes. Both TNFa and interleukin-1 beta (IL-1b) are potent releasers of IL-6. IL-6, on the other hand, once released, feeds back to down-regulate the release of TNFa and IL-1b giving it an antiinflammatory, as well as a proinflammatory role. Increased IL-6 leads to loss of muscle and bone mass, fever, activation of the hypothalamic-pituitary-adrenal axis, activation of the hepatic acute phase response, and hemodilution, resulting in a decline in hemoglobin levels (23–26). In bone, IL-6 is produced by osteoblasts and promotes osteoclast activity and subsequent bone resorption (27). Testosterone, which declines with aging in men (28,29), suppresses IL-6 production from bone (30). Parathyroid hormone levels, which increase with the age-associated decline in vitamin D (31), increase the production of IL-6 from osteoblasts (32). Parathyroid hormone also results in hepatic production of IL-6 and its soluble receptor (33). In older persons, elevated IL-6 levels have been shown cross-sectionally to be inversely associated with muscle mass and strength, physical performance, balance, and walking speed, and positively associated with death (13,35–37). Ferrucci and colleagues (38) reported in a cross-sectional study that elevated IL-6 levels predicted

Behavioral Deficits During Early Stages of Aging in Caenorhabditis elegans Result From Locomotory Deficits Possibly Linked to Muscle Frailty

Abstract: Many behavioral responses require the coordination of sensory inputs with motor outputs. Aging is associated with progressive declines in both motor function and muscle structure. However, the consequences of age-related motor deficits on behavior have not been clearly defined. Here, we examined the effects of aging on behavior in the nematode, Caenorhabditis elegans. As animals aged, mild locomotory deficits appeared that were sufficient to impair behavioral responses to sensory cues. In contrast, sensory ability appeared well maintained during aging. Age-related behavioral declines were delayed in animals with mutations in the daf-2/insulin-like pathway governing longevity. A decline in muscle tissue integrity was correlated with the onset of age-related behavioral deficits, although significant muscle deterioration was not. Treatment with a muscarinic agonist significantly improved locomotory behavior in aged animals, indicating that improved neuromuscular signaling may be one strategy for reducing the severity of age-related behavioral impairments.

Hormone-Treated Snell Dwarf Mice Regain Fertility But Remain Long Lived and Disease Resistant

Abstract: Snell dwarf mice have multiple hormonal deficits, but the way in which these deficits postpone aging are still uncertain. In this study, Snell dwarf mice received 11 weeks of growth hormone and thyroxine injections that increased their weight by approximately 45%, although they remained much smaller than controls. The hormone treatment also restored fertility to male dwarf mice. Despite these effects on growth and maturation, the hormone treatments did not diminish life span or lower the resistance of dwarf mice to cataracts and kidney disease. Administration of thyroxine in food throughout adult life did diminish longevity of Snell dwarf mice, although these mice remain longer lived than control animals. These results show that a 45% increase in body size does not impair longevity or disease resistance for dwarf mice of either sex, and that the exceptional longevity of Snell dwarf mice does not, at least for males, depend on prepubertal immaturity.

Refining the Categorization of Physical Functional Status: The Added Value of Combining Self-Reported and Performance-Based Measures

Abstract: Background. When considered individually, self-reported functional status and performance-based functional status predict functional status decline and mortality. However, what additional prognostic information is gained by combining these approaches remains unknown. Methods. The authors used three waves of three sites (5138 participants) of the Established Populations for Epidemiologic Studies of the Elderly to determine the prognostic value of individual and combined approaches. Baseline self-reported (mobility and activities of daily living [ADL] items) and performance-based (Physical Performance Score) functional status information was classified into three and four hierarchical categories, respectively. Results. Based on self-reported information alone, at 1 year, 73% participants had not changed, 15% declined, 6% improved, and 6% died. At 4 years, 53% had not changed, 24% declined, 2% improved, and 22% died. Based on performance-based assessment alone, at 4 years, 33% of the sample remained stable, 37% declined, 6% improved, and 24% died. In the top two self-reported categories, functioning on the performance-based assessment varied widely. Among those who were independent in all self-reported functioning, approximately 40% scored in each of the top two performance-based categories. Among persons in the top two self-reported categories, poorer performance was associated with progressively higher 1-year and 4-year mortality rates. Among persons with impaired mobility and at least 1 ADL dependency, the mortality rate was high and was not influenced by performance-based score. Conclusions. Combining self-reported and performance-based measurements can refine prognostic information, particularly among older persons with high self-reported functioning. However, if ADL dependency is present, performance-based measures do not add prognostic value regarding mortality.

Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men

Abstract: We investigated the association of vitamin D receptor (VDR) genotype with fat-free mass (FFM) in a cohort of 302 older (aged 58-93 years) Caucasian men who underwent body composition analysis by dual-energy X-ray absorptiometry, and completed questionnaires addressing comorbidities, physical activity, and dietary intake. All participants were genotyped for a VDR translation start site (FokI) polymorphism [FF (37.7%), Ff (48.4%), and ff (13.9%)] and the previously studied BsmI polymorphism [BB (24.9%), Bb (37.7%), and bb (37.4%)]. The BsmI polymorphism was not associated with FFM in any analysis; however, the FokI polymorphism was significantly associated with total FFM, appendicular FFM, and relative (kg/m(2)) appendicular FFM (all p <.05), with the FF group demonstrating significantly lower FFM than the Ff and ff groups (e.g., total FFM: FF = 57.6 +/- 0.4, Ff = 59.4 +/- 0.4, ff = 59.4 +/- 0.7 kg; p <.02). Age-adjusted logistic regression revealed a 2.17-fold higher risk for sarcopenia (defined previously as appendicular FFM <7.26 kg/m(2)) in FF homozygotes (95% CI [confidence interval] = 1.19-3.85; p =.03) compared to men with one or more f alleles. The VDR translation start site (FokI) polymorphism is significantly associated with FFM and sarcopenia in this cohort of older Caucasian men.

Effects of Testosterone on Behavior, Depression, and Cognitive Function in Older Men With Mild Cognitive Loss

Abstract: Background. The role of sex hormones in the prevention of cognitive decline is uncertain. Animal studies suggest mechanisms for sex hormones including testosterone to maintain optimal cognitive function. But, there are studies to suggest that endogenous testosterone levels are associated with aggression in men with cognitive impairment. Methods. In this pilot study, 11 men (mean age 80 6 5 years, range 73‐87 years) with early cognitive decline and bioavailable testosterone levels below 128 ng/dl (lower limit for adult normal range) were randomized to receive intramuscular testosterone (200 mg every 3 weeks) or placebo for 12 weeks. Outcome measures included sex hormones (testosterone, bioavailable testosterone, sex hormone binding globulin, estradiol, and estrone), Behave AD Questionnaire, Katz Activities of Daily Living, Geriatric Depression Scale, Digit Span, Clock Face Drawing, Clock Face Perception, Verbal Fluency, Trail-Making B, and International Prostate Symptom Score at baseline, 4 weeks, and 10 weeks. Results. All men completed the study. Total and bioavailable testosterone, estrone, and estradiol levels increased in men receiving testosterone, but no changes were detected in men receiving placebo. No significant changes were found in behavior following testosterone supplementation, nor was there evidence of change in depression or activities of daily living. No discernable changes were found in any of the cognitive tests. Symptoms of prostate hyperplasia remained unchanged in the testosterone (6.6 þ 5.8 to 5.2 þ 3.6; p ¼ .39) and placebo (8.8 þ 6.4 to 6.4 þ 3.8; p ¼ .15) groups, and prostate-specific antigen levels did not change significantly. Conclusion. No significant changes in behavior, function, depression, or cognitive performance occurred following 12 weeks of testosterone replacement in men with low testosterone levels and early-to-moderate cognitive impairment. This pilot work suggests that testosterone can be given to men with early cognitive impairment without significant concern about worsening aggressive or unwanted behaviors.