Studies suggest that physically active people have reduced risk of incident cognitive impairment in late life. However, these studies are limited by reliance on subjective self-reports of physical activity, which only moderately correlate to objective measures and often exclude activity not readily quantifiable by frequency and duration. The objective of this study was to investigate the relationship between activity energy expenditure (AEE), an objective measure of total activity, and incidence of cognitive impairment.
We calculated AEE as 90% of total energy expenditure (assessed over two weeks using doubly-labeled water) minus resting metabolic rate (measured using indirect calorimetry) in 197 men and women (mean 74.8 years) who were free of mobility and cognitive impairments at study baseline (1998–2000). Cognitive function was assessed at baseline and 2 or 5 years later using the Modified Mini-Mental State Examination (3MS). Cognitive impairment was defined as a decline of >1.0 SD (9 points) between baseline and follow-up.
After adjustment for baseline 3MS, demographics, fat free mass, sleep duration, self-reported health, and diabetes, older adults in the highest sex-specific tertile of AEE had lower odds of incident cognitive impairment than those in the lowest tertile (OR, 95% CI 0.09, 0.01–0.79). There was also a significant dose response between AEE and incidence of cognitive impairment (p-for-trend over tertiles=0.05).
These findings indicate that greater activity energy expenditure may be protective against cognitive impairment in a dose-response manner. The significance of overall activity in contrast to vigorous or light activity should be determined.
Resting metabolic rate (RMR) contributes 60–80% of total energy expenditure and is consistently lower in populations of African descent compared with populations of European populations. Determination of European ancestry (EA) through SNP analysis would provide an initial step for identifying genetic associations that contribute to low RMR. We sought to evaluate the association between RMR and EA in African Americans.
RMR was measured by indirect calorimetry in 141 African American men and women (aged 74.7 ± 3.0 years) enrolled in a substudy of the Health, Aging and Body Composition Study. Ancestry informative markers were used to estimate individual percent EA. Multivariate regression was used to assess the association between RMR and EA after adjustments for soft tissue fat-free mass (STFFM), fat mass, age, study site, physical activity level and sex.
Mean EA was 23.8 ± 16% (range: 0.1% to 70.7%) and there were no differences by sex. Following adjustments, each percent EA was associated with a 1.6 kcal/day (95% Confidence interval: 0.42, 2.7 kcal/day) higher RMR (p = 0.008). This equates to a 160 kcal/day lower RMR in a population of completely African ancestry with one of completely European ancestry. Additional adjustment for trunk STFFM that partially accounts for high-metabolic rate organs did not affect this association.
European ancestry in African Americans is strongly associated with higher RMR. The data suggest that population differences in RMR may be due to genetic variants.
Admixture; energy metabolism; body composition; genetic mapping
Resistance exercise (RE) stimulates growth hormone (GH) secretion in a load-dependent manner, with heavier loads producing larger GH responses. However, new research demonstrates that low-load RE performed with blood flow restriction (BFR) produces potent GH responses that are similar to or exceed those produced following high-load RE. We hypothesized that low-load RE with vascular restriction would attenuate the known age-related reduction in GH response to RE.
In a randomized crossover design, ten young (28±7.8 years) and ten older (67.4±4.6 years) men performed bilateral knee extension RE with low-load [20% of one-repetition maximum (1RM)] with BFR and high-load (80% 1RM) without BFR. GH and lactate were measured every 10 minutes throughout a 150-minute testing session (30 minutes prior to and 120 minutes following completion of the exercise); IGF-I was measured at baseline and 60 minutes post-exercise.
Area under the GH curve indicated that both age groups responded similarly to each exercise condition. However, young men had a significantly greater maximal GH response to low-load RE with BFR than the high-load condition without BFR. Additionally, younger men had greater maximal GH concentrations to low-load RE with BFR than older men (p=0.02). The GH responses were marginally correlated to lactate concentration (r=0.13, p=0.002) and IGF-I levels were unchanged with RE.
GH responses to low-load RE with vascular restriction are slightly higher than high-load RE without vascular restriction in young men. However, low-load RE with vascular restriction did not attenuate the known age-related reduction in GH response with exercise. These data suggest that while low-load RE with vascular restriction is as effective for inducing a GH response than traditionally-based high-load RE, there is a more potent response in young men.
KAATSU; Blood flow restriction; muscle; growth hormone; vascular; hypoxia; ischemia; endocrine
There is a shortage of information on metabolic costs of daily physical activities in older adults and the effect of having mobility impairments. The primary purpose of this study was to evaluate metabolic equivalent (MET) values on common daily tasks in men and women aged > 70 years compared to normative criteria. A secondary purpose was to determine the effect of having mobility impairments.
Cross-sectional observational study.
University based research clinic
Forty-five participants aged 70 to 90 years of age (mean: 76.3 ± 5.1) volunteered to complete 17 daily activities, each lasting 10 minutes.
Oxygen consumption (VO2 = ml•kg−1•min−1) was measured through a mask by a portable gas analyzer and MET values were calculated as measured VO2/3.5 ml•kg−1•min−1. Values were compared to both normative values and between participants with and without mobility impairments.
Compared to the established normative criteria, measured METs were different in 14 of 17 tasks performed. Compared to measured METs, normative values underestimated walking leisurely (0.87 ± 0.12 METs) walking briskly (0.87 ± 0.12 METs ), and bed making (1.07 ± 0.10 METs ), but overestimated gardening (1.46 ± 0.12 METs) and climbing stairs (0.73 ± 0.18). Participants with impairments had significantly lower METs while gardening, vacuuming/sweeping, stair climbing, and walking briskly. However, when METs were adjusted for performance speed the metabolic costs were 16–27% higher for those with mobility impairments.
Compared to normative values, metabolic costs of daily activities are substantially different in older adults and having mobility impairments increases this metabolic cost. These results may have implications for practitioners to appropriately prescribe daily physical activities for healthy and mobility impaired older adults.
Energy expenditure; Aging; Disability; Metabolic Efficiency
In 2008, we published an article arguing that the age-related loss of muscle strength is only partially explained by the reduction in muscle mass and that other physiologic factors explain muscle weakness in older adults (Clark BC, Manini TM. Sarcopenia =/= dynapenia. J Gerontol A Biol Sci Med Sci. 2008;63:829–834). Accordingly, we proposed that these events (strength and mass loss) be defined independently, leaving the term “sarcopenia” to be used in its original context to describe the age-related loss of muscle mass. We subsequently coined the term “dynapenia” to describe the age-related loss of muscle strength and power. This article will give an update on both the biological and clinical literature on dynapenia—serving to best synthesize this translational topic. Additionally, we propose a working decision algorithm for defining dynapenia. This algorithm is specific to screening for and defining dynapenia using age, presence or absence of risk factors, a grip strength screening, and if warranted a test for knee extension strength. A definition for a single risk factor such as dynapenia will provide information in building a risk profile for the complex etiology of physical disability. As such, this approach mimics the development of risk profiles for cardiovascular disease that include such factors as hypercholesterolemia, hypertension, hyperglycemia, etc. Because of a lack of data, the working decision algorithm remains to be fully developed and evaluated. However, these efforts are expected to provide a specific understanding of the role that dynapenia plays in the loss of physical function and increased risk for disability among older adults.
Strength; Weakness; Atrophy; Function; Disability
Classic developmental theory suggests that aging is associated with using compensatory strategies to prolong independence. While compensatory strategies are typically considered positive adaptations, they also signify an early phase in the disablement process — commonly known as pre-clinical disability. To build a better understanding of psychological constructs related to these early signs of disability, we examined the contribution of self-efficacy and state anxiety on using compensatory strategies among pre-clinically disabled older adults. Compensatory strategies were observed during performance of daily activities in 257 pre-clinically disabled older adults (67.6 ± 7.04), and self-efficacy and state anxiety were evaluated prior to performing each task. In univariate models, lower self-efficacy and higher anxiety were associated with more compensation (Spearman correlations: 0.15-0.48, p < 0.05). Multivariate logistic regression indicated that low self-efficacy [Odds Ratio (OR): 1.70; 95% Confidence Interval (CI): 1.40-2.08) and high anxiety (OR: 1.34; 95% CI: 1.10-1.63) were positively associated with using ≥ 6 compensatory strategies – a level signifying substantial compensation. When considered jointly with self-efficacy, the association with anxiety was reversed— higher anxiety demonstrated a lower likelihood of using compensation (OR: 0.70-0.73; 95% CI: 0.50-0.99). The addition of self-efficacy might remove the self-defeating cognitions characterizing anxiety allowing the remaining arousal component to appear beneficial. In conclusion, lower self-efficacy and higher anxiety are associated with using compensation to complete daily tasks among pre-clinically disabled older adults. Such psychological constructs may contribute to the use of compensatory strategies and represent future intervention targets to help reduce early signs of disability.
disablement; confidence; state anxiety; functional task modification
Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.
Aging; Proteolysis; Satellite Cells; HIV; COPD; Disability
Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly (HFE) participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in COX activity. Levels of key metabolic regulators, SIRT3 and PGC-1α were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects, however no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery (PIM) components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways, and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.
aging; sarcopenia; mitochondria; skeletal muscle; PGC-1α
The Lifestyle Interventions and Independence for Elders (LIFE) Study is a Phase III randomized controlled clinical trial (Clinicaltrials.gov identifier: NCT01072500) that will provide definitive evidence regarding the effect of physical activity (PA) on major mobility disability in older adults (70–89 years old) who have compromised physical function. This paper describes the methods employed in the delivery of the LIFE Study PA intervention, providing insight into how we promoted adherence and monitored the fidelity of treatment. Data are presented on participants’ motives and self-perceptions at the onset of the trial along with accelerometry data on patterns of PA during exercise training. Prior to the onset of training, 31.4% of participants noted slight conflict with being able to meet the demands of the program and 6.4% indicated that the degree of conflict would be moderate. Accelerometry data collected during PA training revealed that the average intensity – 1,555 counts/minute for men and 1,237 counts/minute for women – was well below the cutoff point used to classify exercise as being of moderate intensity or higher for adults. Also, a sizable subgroup required one or more rest stops. These data illustrate that it is not feasible to have a single exercise prescription for older adults with compromised function. Moreover, the concept of what constitutes “moderate” exercise or an appropriate volume of work is dictated by the physical capacities of each individual and the level of comfort/stability in actually executing a specific prescription.
aging; accelerometry; physical disability; compromised physical function; older adults
The decline in activity energy expenditure underlies a range of age-associated pathological conditions, neuromuscular and neurological impairments, disability, and mortality. The majority (90%) of the energy needs of the human body are met by mitochondrial oxidative phosphorylation (OXPHOS). OXPHOS is dependent on the coordinated expression and interaction of genes encoded in the nuclear and mitochondrial genomes. We examined the role of mitochondrial genomic variation in free-living activity energy expenditure (AEE) and physical activity levels (PAL) by sequencing the entire (~16.5 kilobases) mtDNA from 138 Health, Aging, and Body Composition Study participants. Among the common mtDNA variants, the hypervariable region 2 m.185G>A variant was significantly associated with AEE (p=0.001) and PAL (p=0.0005) after adjustment for multiple comparisons. Several unique nonsynonymous variants were identified in the extremes of AEE with some occurring at highly conserved sites predicted to affect protein structure and function. Of interest is the p.T194M, CytB substitution in the lower extreme of AEE occurring at a residue in the Qi site of complex III. Among participants with low activity levels, the burden of singleton variants was 30% higher across the entire mtDNA and OXPHOS complex I when compared to those having moderate to high activity levels. A significant pooled variant association across the hypervariable 2 region was observed for AEE and PAL. These results suggest that mtDNA variation is associated with free-living AEE in older persons and may generate new hypotheses by which specific mtDNA complexes, genes, and variants may contribute to the maintenance of activity levels in late life.
metabolic rate; energy expenditure; mitochondria; mtDNA; oxidative phosphorylation; DNA sequencing
Aerobic exercise has been suggested to ameliorate aging-related decline in humans. Recently, evidence has indicated chronological aging is associated with decreases in measures of interhemispheric inhibition during unimanual movements, but that such decreases may be mitigated by long-term physical fitness. The present study investigated measures of ipsilateral (right) primary motor cortex activity during right-hand movements using functional magnetic resonance imaging and transcranial magnetic stimulation (TMS). Healthy, right-handed participant groups were comprised of 12 sedentary older adults, 12 physically active older adults, and 12 young adults. Active older adults and younger adults evidenced longer ipsilateral silent periods (iSP) and less positive BOLD of ipsilateral motor cortex (iM1) as compared to sedentary older adults. Across groups, duration of iSP from TMS was inversely correlated with BOLD activity in iM1 during unimanual movement. These findings suggest that increased physical activity may have a role in decreasing aging-related losses of interhemispheric inhibition.
Aging; Physical activity; fMRI; TMS; Interhemispheric communication
Very little is known about the longitudinal changes in energy requirements in late life. The purposes of this study were to: (1) determine the energy requirements in late life and how they changed during a 7 year time-span, (2) determine whether changes in fat free mass (FFM) were related to changes in resting metabolic rate (RMR), and (3) determine the accuracy of predicted total energy expenditure (TEE) to measured TEE.
TEE was assessed via doubly labeled water (DLW) technique in older adults in both 1999 (n = 302; age: 74 ± 2.9 yrs) and again in 2006 (n = 87 age: 82 ± 3.1 yrs). RMR was measured with indirect calorimetry, and body composition was assessed with dual-energy x-ray absorptiometry.
The energy requirements in the 9th decade of life were 2208 ± 376 kcal/d for men and 1814 ± 337 kcal/d for women. This was a significant decrease from the energy requirements in the 8th decade of life in men (2482 ± 476 kcal/d vs. 2208 ± 376 kcal/d) but not in women (1892 ± 271 kcal/d vs. 1814 ± 337 kcal/d). In addition to TEE, RMR, and activity EE (AEE) also decreased in men, but not women, while FFM decreased in both men and women. The changes in FFM were correlated with changes in RMR for men (r = 0.49, p < 0.05) but not for women (r = −0.08, ns). Measured TEE was similar to Dietary Reference Intake (DRI) predicted TEE for men (2208 ± 56 vs. 2305 ± 35 kcal/d) and women (1814 ± 42 vs. 1781 ± 20 kcal/d). However, measured TEE was different than the World Health Organization (WHO) predicted TEE in men (2208 ± 56 vs. 2915 ± 31 kcal/d (p < 0.05)) and women (1814 ± 42 vs. 2315 ± 21 kcal/d (p < 0.05)).
TEE, RMR and AEE decreased in men, but not women, from the 8th to 9th decade of life. The DRI equation to predict TEE was comparable to measured TEE, while the WHO equation over-predicted TEE in our elderly population.
Doubly labeled water; Energy expenditure; Elderly; Energy requirements
In this study, the authors aimed to determine whether higher activity energy expenditure, assessed by using doubly labeled water, was associated with a reduced decline in mobility limitation among 248 older community-dwelling US adults aged 70–82 years enrolled in 1998–1999. Activity energy expenditure was calculated as total energy expenditure (assessed over 2 weeks by using doubly labeled water) minus resting metabolic rate (measured with indirect calorimetry), with adjustment for the thermic effect of food. Across sex-specific tertiles of activity energy expenditure, men in the lowest activity group experienced twice the rate of mobility limitation as men in the highest activity group (41% (n = 18) vs. 18% (n = 8)). Conversely, women in the lowest and highest activity groups exhibited similarly high rates of mobility limitation (40% (n = 16) vs. 38% (n = 15)). After adjustment for potential confounders, men with higher activity energy expenditure levels continued to show reduced risk of mobility limitation (per standard deviation (284 kcal/day): hazard ratio = 0.61, 95% confidence interval: 0.41, 0.92). Women showed no association (per standard deviation (226 kcal/day): hazard ratio = 1.34, 95% confidence interval: 0.98, 1.85). Greater energy expenditure from any and all physical activity was significantly associated with reduced risk of developing mobility limitation among men, but not among women.
aging; disability evaluation; energy metabolism; exercise; mobility limitation; motor activity; sex
Dynapenia (pronounced dahy-nuh-pē-nē-a, Greek translation for poverty of strength, power, or force) is the age-associated loss of muscle strength that is not caused by neurologic or muscular diseases. Dynapenia predisposes older adults to an increased risk for functional limitations and mortality. For the past several decades, the literature has largely focused on muscle size as the primary cause of dynapenia; however, recent findings have clearly demonstrated that muscle size plays a relatively minor role. Conversely, subclinical deficits in the structure and function of the nervous system and/or impairments in the intrinsic force-generating properties of skeletal muscle are potential antecedents to dynapenia. This review highlights in the contributors to dynapenia and the etiology and risk factors that predispose individuals to dynapenia. In addition, we address the role of nutrition in the muscular and neurologic systems for the preservation of muscle strength throughout the life span.
Aging; Strength; Weakness; Function; Muscle; Disability; Sarcopenia; Dynapenia
The objective of this study is to evaluate the effects of blood flow restriction (BFR) on muscle oxygenation during low-intensity resistance exercise as well as postexercise expression of molecules related to physiological angiogenesis.
Using a randomized cross-over design, six apparently healthy young adults (22 ± 1 yr) performed 120 unilateral knee extensions at 40% of 1 repetition maximum with and without BFR (CNTRL). Near-infrared spectroscopy was used to measure oxygenation of the vastus lateralis during exercise. Serum and muscle expression of Post–Resistance vascular endothelial growth factor (VEGF) were determined preexercise, 4 h postexercise, and 24 h postexercise. Transcript (mRNA) expression of VEGF and other angiogenic genes was also determined.
BFR increased muscle hemoglobin (Hb) concentrations during exercise (14.4 ± 1.6 vs. 0.9 ± 1.6, P = 0.002), driven largely by an increase in deoxygenated Hb (11.0 ± 2.5 vs. 0.5 ± 1.1, P = 0.030). BFR also increased (P < 0.05) transcript expression of VEGF, VEGF-R2, hypoxia-inducible factor 1 alpha, inducible nitric oxide synthase (NOS), and neuronal NOS. The most dramatic change in response to BFR was an increase in VEGF mRNA at 4 h postexercise (4.1 ± 0.6 vs. 0.6 ± 0.2-fold change, P = 0.028). Compared with control, transcript expression of endothelial NOS, serum VEGF, or muscle protein expression of VEGF was not altered in response to BFR (P > 0.05).
Acute BFR increases postexercise expression of mRNA related to skeletal muscle angiogenesis, plausibly in response to changes in muscle Hb concentrations.
BFR; KAATSU; SKELETAL MUSCLE; RESISTANCE EXERCISE; NIRS; VEGF; NOS
To assess the association between angiotensin converting enzyme inhibitors (ACEis) and improvements in the physical function of older adults in response to chronic exercise training.
Secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study, a multisite randomized clinical trial to evaluate the effects of chronic exercise on the physical function of older adults at risk for mobility disability.
Four academic research centers within the United States.
Four hundred twenty-four individuals aged 70 to 89 with mild to moderate functional impairments categorized for this analysis as ACEi users, users of other antihypertensive drugs, or antihypertensive nonusers.
A 12-month intervention of structured physical activity (PA) or health education promoting successful aging (SA).
Change in walking speed during a 400-m test and performance on a battery of short-duration mobility tasks (Short Physical Performance Battery (SPPB)).
Physical activity significantly improved the adjusted walking speed of ACEi users (P < .001) but did not of nonusers. PA improved the adjusted SPPB score of ACEi users (P < .001) and of persons who used other antihypertensive drugs (P = .005) but not of antihypertensive nonusers (P = .91). The percentage of ACEi users deriving clinically significant benefit from exercise training for walking speed (30%) and SPPB score (48%) was dramatically higher than for nonusers (14% and 12%, respectively).
For older adults at risk for disability, exercise-derived improvements in physical function were greater for ACEi users than users of other antihypertensive drugs and antihypertensive nonusers.
aging; exercise; physical function; LIFE Study; ACE inhibitors
Timing of assessment of psychological construct is controversial and results differ based on the model of pain induction. Previous studies have not used an exercise induced injury model to investigate timing of psychological assessment. Exercise induced injury models may be appropriate for these investigations because they approximate clinical pain conditions better than other experimental stimuli. In this study we examined the changes of psychological constructs over time and determined whether timing of assessment affected the construct’s association with reports of pain intensity and disability. One-hundred twenty-six healthy volunteers completed the Fear of Pain Questionnaire (FPQ-III), Pain Catastrophizing Scale (PCS), and Tampa Scale of Kinesiophobia (TSK) prior to inducing muscle injury to the shoulder. The PCS and TSK were measured again 48 and 96 hours post-injury induction. Pain intensity and disability were collected at 48 and 96 hours and served as dependent variables in separate regression models. Results indicated that the FPQ-III had the strongest prediction of pain intensity from baseline to 96 hours. After baseline the PCS and TSK were stronger predictors of pain intensity and disability, respectively. These data provide support for the use of psychological constructs in predicting outcomes from shoulder pain. However, they deviate from the current theoretical model indicating that fear of pain is a consequence of injury and instead suggests that fear of pain before injury may influence reports of pain intensity.
The current study provides evidence that fear of pain can be assessed prior to injury. Furthermore, it supports that after injury pain catastrophizing and kinesiophobia are independently associated with pain and disability. Overall these data suggest that timing of psychological assessment may be an important consideration in clinical environments.
Fear; catastrophizing; assessment; pain; disability
To examine the association between the use of compensatory strategies to successfully complete common daily activities — an indicator of pre-clinical disability— and body mass in pre-clinically disabled older adults.
Cross-sectional observational study.
Two-hundred and fifty-nine pre-clinically disabled older adults defined as having changed the frequency or manner of performing daily tasks without reporting any difficulty.
The use of compensatory strategies were objectively evaluated using the MOD scale — a reliable and valid scale for assessing the manner in which common daily activities were completed. Height and weight were measured to classify participants into the following body mass index (BMI) categories: 1) normal: 18.5–24.9kg/m2, 2) overweight: 25.0–29.9kg/m2, 3) obese class I: 30.0–34.9kg/m2, and 4) obese class II: 35.0–39.9kg/m2.
Compared to other BMI categories, individuals with class II obesity demonstrated a significantly higher probability of using ≥ 1 compensatory strategies when rising from a chair (30cm height), kneel to stand, stair ascent, stair descent, and supine to stand tasks. When summarized over all tasks, individuals with class II obesity were 18 times more likely to use extensive compensatory strategies (≥ 6 on MOD scale) compared to normal weight older adults. Similar trends at a lesser magnitude were found in obese and overweight compared to normal weight older adults.
Obesity is associated with extensive use of compensatory strategies when performing common daily tasks prior to the onset of perceived difficulty, thus placing them at higher risk of disability compared to their peers with lower body mass.
Body mass; Functional task modification; Disablement; preclinical disability; obesity; compensatory strategies
Physical fitness has been long associated with maintenance and improvement of motor performance as we age. In particular, measures of psychomotor speed and motor dexterity tend to be higher in physically fit aging adults as compared to their sedentary counterparts. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS), we explored the patterns of neural activity that may, in part, account for differences between individuals of varying physical fitness levels. In this study, we enrolled both sedentary and physically fit middle age (40–60) and younger (18–30) adults and measured upper extremity motor performance during behavioral testing. In a follow-up session, we employed TMS and fMRI to assess levels of interhemispheric communication during unimanual tasks. Results show that increased physical fitness is associated with better upper extremity motor performance on distal dexterity assessments and increased levels of interhemispheric inhibition in middle age adults. Further, the functional correlates of changes of ipsilateral activity appears to be restricted to the aging process as younger adults of varying fitness levels do not differ in hemispheric patterns of activity or motor performance. We conclude that sedentary aging confers a loss of interhemispheric inhibition that is deleterious to some aspects of motor function, as early as midlife, but these changes can be mediated by chronic engagement in aerobic exercise.
aging neuroscience; aging; fMRI; TMS; physical fitness; interhemispheric communication; negative BOLD; dexterity
The lower extremities are important to performing physical activities of daily life. This study investigated lower extremity tissue composition, i.e. muscle and fat volumes, in young and older adults and the relative importance of individual tissue compartments to the physical function of older adults. A total of 43 older (age 78.3 ± 5.6 yr) and 20 younger (age 23.8 ± 3.9 yr) healthy men and women participated in the study. Older participants were further classified as either high- (HF) or low-functioning (LF) according to the Short Physical Performance Battery (SPPB). Magnetic resonance images were used to determine the volumes of skeletal muscle, subcutaneous fat (SAT), and intermuscular fat (IMAT) in the thigh (femoral) and calf (tibiofibular) regions. After adjusting for the sex of participants, younger participants had more femoral muscle mass than older adults (p < 0.001 for between group differences) as well as less femoral IMAT (p = 0.008) and tibiofibular IMAT (p < 0.001). Femoral muscle was the only tissue compartment demonstrating a significant difference between the two older groups, with HF participants having 31% more femoral muscle mass than LF participants (mean difference = 103.0 ± 34.0 cm3; p = 0.011). In subsequent multiple regression models including tissue compartments and demographic confounders, femoral muscle was the primary compartment associated with both SPPB score (r2 = 0.264, p= 0.001) and 4-meter gait speed (r2 = 0.187, p= 0.007). These data suggest that aging affects all lower extremity compartments, but femoral muscle mass is the major compartment associated with physical function in older adults.
Aging; Sarcopenia; Older Adults; Disability; SPPB; IMAT
Reduced gait speed is associated with falls, late-life disability, hospitalization/institutionalization and cardiovascular morbidity and mortality. Aging is also accompanied by a widening of pulse pressure (PP) that contributes to ventricular-vascular uncoupling. The purpose of this study was to test the hypothesis that PP is associated with long-distance gait speed in community-dwelling older adults in the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study.
Brachial blood pressure and 400-meter gait speed (average speed maintained over a 400-meter walk at “usual” pace) were assessed in 424 older adults between the ages of 70–89 yrs at risk for mobility disability (mean age = 77 yrs; 31% male). PP was calculated as systolic blood pressure (BP) – diastolic BP.
Patients with a history of heart failure and stroke (n = 42) were excluded leaving 382 participants for final analysis. When categorized into tertiles of PP, participants within the highest PP tertile had significantly slower gait speed than those within the lowest PP tertile (p<0.05). Following stepwise multiple regression, PP was significantly and inversely associated with 400-meter gait speed (p<0.05). Other significant predictors of gait speed included: handgrip strength, body weight, age and history of diabetes mellitus (p<0.05). Mean arterial pressure, systolic BP and diastolic BP were not predictors of gait speed.
Pulse pressure is associated long-distance gait speed in community-dwelling older adults. Vascular senescence and altered ventricular-vascular coupling may be associated with the deterioration of mobility and physical function in older adults.
Objective methods to measure daily energy expenditure in studies of aging are needed. We sought to determine the accuracy of total energy expenditure (TEE) and activity energy expenditure (AEE) estimates from the SenseWear Pro armband (SWA) using software versions 6.1 (SWA 6.1) and 5.1 (SWA 5.1) relative to criterion methods in free-living older adults.
Participants (n = 19, mean age 82.0 years) wore a SWA for a mean ± SD 12.5 ± 1.1 days, including while sleeping. During this same period, criterion values for TEE were assessed with doubly labeled water and for resting metabolic rate (RMR) with indirect calorimetry. AEE was calculated as 0.9 TEE – RMR.
For TEE, there was no difference in mean ± SD values from doubly labeled water (2,040 ± 472 kcal/day) versus SWA 6.1 (2,012 ± 497 kcal/day, p = .593) or SWA 5.1 (2,066 ± 474 kcal/day, p = .606); individual values were highly correlated between methods (SWA 6.1 r = .893, p < .001; SWA 5.1 r = .901, p < .001) and demonstrated strong agreement (SWA 6.1 intraclass correlation coefficient = .896; SWA 5.1 intraclass correlation coefficient = .904). For AEE, mean values from SWA 6.1 (427 ± 304 kcal/day) were lower by 26.8% than criterion values (583 ± 242 kcal/day, p = .003), and mean values from SWA 5.1 (475 ± 299 kcal/day) were lower by 18.5% than criterion values (p = .021); however, individual values were highly correlated between methods (SWA 6.1 r = .760, p < .001; SWA 5.1 r = .786, p < .001) and demonstrated moderate agreement (SWA 6.1 intraclass correlation coefficient = .645; SWA 5.1 intraclass correlation coefficient = .720). Bland–Altman plots identified no systematic bias for TEE or AEE.
Acceptable levels of agreement were observed between SWA and criterion measurements of TEE and AEE in older adults.
Accelerometer; Activity monitor; Physical activity; Aged; DLW
Obese older adults are particularly susceptible to sarcopenia and have a higher prevalence of disability than their peers of normal weight. Interventions to improve body composition in late life are crucial to maintaining independence. The main mechanisms underlying sarcopenia have not been determined conclusively, but chronic inflammation, apoptosis, and impaired mitochondrial function are believed to play important roles. It has yet to be determined whether impaired cellular quality control mechanisms contribute to this process. The objective of this study was to assess the effects of a 6-month weight loss program combined with moderate-intensity exercise on the cellular quality control mechanisms autophagy and ubiquitin-proteasome, as well as on inflammation, apoptosis, and mitochondrial function, in the skeletal muscle of older obese women. The intervention resulted in significant weight loss (8.0 ± 3.9 % vs. 0.4 ± 3.1% of baseline weight, p = 0.002) and improvements in walking speed (reduced time to walk 400 meters, − 20.4 ± 16% vs. − 2.5 ± 12%, p = 0.03). In the intervention group, we observed a three-fold increase in messenger RNA (mRNA) levels of the autophagy regulators LC3B, Atg7, and lysosome-associated membrane protein-2 (LAMP-2) compared to controls. Changes in mRNA levels of FoxO3A and its targets MuRF1, MAFBx, and BNIP3 were on average seven-fold higher in the intervention group compared to controls, but these differences were not statistically significant. Tumor necrosis factor-α (TNF-α) mRNA levels were elevated after the intervention, but we did not detect significant changes in the downstream apoptosis markers caspase 8 and 3. Mitochondrial biogenesis markers (PGC1α and TFAm) were increased by the intervention, but this was not accompanied by significant changes in mitochondrial complex content and activity. In conclusion, although exploratory in nature, this study is among the first to report the stimulation of cellular quality control mechanisms elicited by a weight loss and exercise program in older obese women.
Preclinical studies strongly suggest that accelerated apoptosis in skeletal myocytes may be involved in the pathogenesis of sarcopenia. However, evidence in humans is sparse. In the present study, we investigated whether apoptotic signaling in the skeletal muscle was associated with indices of muscle mass and function in older persons.
Community-dwelling older adults were categorized into high-functioning (HF) or low-functioning (LF) groups according to their short physical performance battery (SPPB) summary score. Participants underwent an isokinetic knee extensor strength test and 3-dimensional magnetic resonance imaging of the thigh. Vastus lateralis muscle samples were obtained by percutaneous needle biopsy and assayed for the expression of a set of apoptotic signaling proteins. Age, sex, number of comorbid conditions and medications as well as knee extensor strength were not different between groups. HF participants displayed greater thigh muscle volume compared with LF persons. Multivariate partial least squares (PLS) regressions showed significant correlations between caspase-dependent apoptotic signaling proteins and the muscular percentage of thigh volume (R2 = 0.78; Q2 = 0.61) as well as gait speed (R2 = 0.81; Q2 = 0.56). Significant variables in the PLS model of percent muscle volume were active caspase-8, cleaved caspase-3, cytosolic cytochrome c and mitochondrial Bak. The regression model of gait speed was mainly described by cleaved caspase-3 and mitochondrial Bax and Bak. PLS predictive apoptotic variables did not differ between functional groups. No correlation was determined between apoptotic signaling proteins and muscle strength or quality (strength per unit volume).
Data from this exploratory study show for the first time that apoptotic signaling is correlated with indices of muscle mass and function in a cohort of community-dwelling older persons. Future larger-scale studies are needed to corroborate these preliminary findings and determine if down-regulation of apoptotic signaling in skeletal myocytes will provide improvements in the muscle mass and functional status of older persons.