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2.  Physical impairment and body weight history in postmenopausal women: The Women's Health Initiative 
Public health nutrition  2016;19(17):3169-3177.
To examine whether weight history and weight transitions over adult lifespan contribute to physical impairment among postmenopausal women.
Body mass index (BMI; kg/m2) categories were calculated among postmenopausal women who reported their weight and height at age 18. Multiple-variable logistic regression was used to determine the association between BMI at age 18 and BMI transitions over adulthood on severe physical impairment (SPI), defined as scoring < 60 on the Physical Functioning Subscale of the Random 36-Item Healthy Survey.
Participants were part of the Women's Health Initiative Observational study (WHI OS), where participants’ health were followed over time via questionnaires and clinical assessments.
Postmenopausal women (n=76,016; 63.5 ± 7.3 years)
Women with overweight (BMI=25.0-29.9) or obesity (BMI≥30) at 18 years had greater odds of SPI [odds ratio (OR) = 1.51, 95% confidence interval (CI): 1.35-1.69 and 2.14, 95% CI: 1.72-2.65, respectively] than normal weight (BMI=18.5-24.9) counterparts. Transitions from normal weight to overweight/obese or to underweight (BMI <18.5) were associated with greater odds of SPI (1.97 [1.84-2.11] and 1.35 [1.06-1.71], respectively) compared to weight stability. Shifting from underweight to overweight/obese also had increased odds of SPI (1.52 [1.11-2.09]). Overweight/obese to normal BMI transitions resulted in a reduced SPI odds (0.52 [0.39-0.71]).
Higher weight history and transitions into higher weight classes were associated with higher likelihood of severe physical impairment, while transitioning into lower weight classes for those with overweight/obesity was protective among postmenopausal women.
PMCID: PMC5135627  PMID: 27269298
Body weight; weight change; body mass index; physical impairment; physical function; disability
3.  Mitochondrial DNA Heteroplasmy Associations With Neurosensory and Mobility Function in Elderly Adults 
Mitochondrial DNA (mtDNA) heteroplasmy is a mixture of normal and mutated mtDNA molecules in a cell. High levels of heteroplasmy at specific mtDNA sites lead to inherited mitochondrial diseases with neurological, sensory, and movement impairments. Here we test the hypothesis that heteroplasmy levels in elderly adults are associated with impaired function resembling mild forms of mitochondrial disease.
We examined platelet mtDNA heteroplasmy at 20 disease-causing sites for associations with neurosensory and mobility function among 137 participants from the community-based Health, Aging, and Body Composition Study.
Elevated mtDNA heteroplasmy at four mtDNA sites in complex I and tRNA genes was nominally associated with reduced cognition, vision, hearing, and mobility: m.10158T>C with Modified Mini-Mental State Examination score (p = .009); m.11778G>A with contrast sensitivity (p = .02); m.7445A>G with high-frequency hearing (p = .047); and m.5703G>A with 400 m walking speed (p = .007).
These results indicate that increased mtDNA heteroplasmy at disease-causing sites is associated with neurosensory and mobility function in older persons. We propose the novel use of mtDNA heteroplasmy as a simple, noninvasive predictor of age-related neurologic, sensory, and movement impairments.
PMCID: PMC4612388  PMID: 26328603
Mitochondrial DNA; Heteroplasmy; Cognition; Vision; Hearing; Mobility.
4.  Successful Aging: Advancing the Science of Physical Independence in Older Adults 
Ageing research reviews  2015;24(0 0):304-327.
The concept of ‘Successful Aging’ has long intrigued the scientific community. Despite this long-standing interest, a consensus definition has proven to be a difficult task, due to the inherent challenge involved in defining such a complex, multi-dimensional phenomenon. The lack of a clear set of defining characteristics for the construct of successful aging has made comparison of findings across studies difficult and has limited advances in aging research. The domain in which consensus on markers of successful aging is furthest developed is the domain of physical functioning. For example, walking speed appears to be an excellent surrogate marker of overall health and predicts the maintenance of physical independence, a cornerstone of successful aging. The purpose of the present article is to provide an overview and discussion of specific health conditions, behavioral factors, and biological mechanisms that mark declining mobility and physical function and promising interventions to counter these effects. With life expectancy continuing to increase in the United States and developed countries throughout the world, there is an increasing public health focus on the maintenance of physical independence among all older adults.
PMCID: PMC4661112  PMID: 26462882
age; mobility; obesity; sarcopenia; healthspan; longevity
5.  Using Physical Activity to Gain the Most Public Health Bang for the Buck 
JAMA internal medicine  2015;175(6):968-969.
PMCID: PMC4659486  PMID: 25844886
6.  Sedentary time is associated with the metabolic syndrome in older adults with mobility limitations — The LIFE Study 
Experimental gerontology  2015;70:32-36.
Epidemiological and objective studies report an association between sedentary time and lower risk of the metabolic syndrome (MetS) and its risk factors in young and middle-age adults. To date, there is a lack of objective data on the association between sedentary time and MetS among older adults.
The association between objectively measured sedentary time (accelerometry) with MetS and MetS components was examined in a large sample of older adults with mobility limitations (N = 1198; mean age = 78.7 ± 5.3 years) enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. Participants were divided into tertiles according to percentage of daily sedentary time, and the relation between sedentary time with MetS and MetS components was examined after adjusting for age, sex, ethnicity, and BMI.
Participants in the highest sedentary time tertile had significantly higher odds of MetS (OR = 1.54) (95% CI 1.13 to 2.11) in comparison with participants in the lowest tertile (p = 0.03). Participants in the highest sedentary time tertile had larger waist circumference (p = 0.0001) and lower HDL-C (p = 0.0003) than participants in the lowest sedentary time tertile.
Sedentary time was strongly related to higher odds of MetS. These results, based on objectively measured sedentary time, suggest that sedentary time may represent an important risk factor for the development of MetS in older adults with high likelihood for disability.
PMCID: PMC4600654  PMID: 26130060
Aging; Accelerometry; Glucose; Disability; Waist circumference
7.  Kaatsu training to enhance physical function of older adults with knee osteoarthritis: Design of a randomized controlled trial 
Contemporary clinical trials  2015;43:217-222.
As the U.S. population ages, efficacious interventions are needed to manage pain and maintain physical function among older adults with osteoarthritis (OA). Skeletal muscle weakness is a primary contributory factor to pain and functional decline among persons with OA, thus interventions are needed that improve muscle strength. High-load resistance exercise is the best-known method of improving muscle strength; however high-compressive loads commonly induce significant joint pain among persons with OA. Thus interventions with low-compressive loads are needed which improve muscle strength while limiting joint stress. This study is investigating the potential of an innovative training paradigm, known as Kaatsu, for this purpose. Kaatsu involves performing low-load exercise while externally-applied compression partially restricts blood flow to the active skeletal muscle. The objective of this randomized, single-masked pilot trial is to evaluate the efficacy and feasibility of chronic Kaatsu training for improving skeletal muscle strength and physical function among older adults. Participants aged ≥ 60 years with physical limitations and symptomatic knee OA will be randomly assigned to engage in a 3-month intervention of either (1) center-based, moderate-load resistance training, or (2) Kaatsu training matched for overall workload. Study dependent outcomes include the change in 1) knee extensor strength, 2) objective measures of physical function, and 3) subjective measures of physical function and pain. This study will provide novel information regarding the therapeutic potential of Kaatsu training while also informing about the long-term clinical viability of the paradigm by evaluating participant safety, discomfort, and willingness to continually engage in the intervention.
PMCID: PMC4522335  PMID: 26111922
Osteoarthritis; Aging; pain; exercise; disability; muscle strength; function
8.  Genetic Moderators of the Impact of Physical Activity on Depressive Symptoms 
Converging evidence suggests that physical activity is an effective intervention for both clinical depression and sub-threshold depressive symptoms; however, findings are not always consistent. These mixed results might reflect heterogeneity in response to physical activity, with some subgroups of individuals responding positively, but not others.
1) To examine the impact of genetic variation and sex on changes in depressive symptoms in older adults after a physical activity (PA) intervention, and 2) determine if PA differentially improves particular symptom dimensions of depression.
Randomized controlled trial.
Four field centers (Cooper Institute, Stanford University, University of Pittsburgh, and Wake Forest University).
396 community-dwelling adults aged 70–89 years who participated in the Lifestyle Interventions and Independence for Elders Pilot Study (LIFE-P).
12-month PA intervention compared to an education control.
Polymorphisms in the serotonin transporter (5-HTT), brain-derived neurotrophic factor (BDNF), and apolipoprotein E (APOE) genes; 12-month change in the Center for Epidemiologic Studies Depression Scale total score, as well as scores on the depressed affect, somatic symptoms, and lack of positive affect subscales.
Men randomized to the PA arm showed the greatest decreases in somatic symptoms, with a preferential benefit in male carriers of the BDNF Met allele. Symptoms of lack of positive affect decreased more in men compared to women, particularly in those possessing the 5-HTT L allele, but the effect did not differ by intervention arm. APOE status did not affect change in depressive symptoms.
Results of this study suggest that the impact of PA on depressive symptoms varies by genotype and sex, and that PA may mitigate somatic symptoms of depression more than other symptoms. The results suggest that a targeted approach to recommending PA therapy for treatment of depression is viable.
PMCID: PMC4905714  PMID: 26980363
exercise intervention; depression; aging; BDNF; APOE; serotonin transporter
9.  Interventions to Reduce Sedentary Behavior 
This paper reports on presentations and discussion from the working group on “Influences on Sedentary Behavior & Interventions” as part of the Sedentary Behavior: Identifying Research Priorities Workshop.
Interventions were discussed in the context of targeting sedentary behavior (SB) as a concept distinct from physical activity (PA). It was recommended that interventions targeting SB should consider a life course perspective, a position predicated on the assumption that SB is age and life stage dependent. Additionally, targeting environments where individuals have high exposure to SB— such as workplace sitting— could benefit from new technology (e.g., computer-based prompting to stand or move), environmental changes (e.g., active workstations), policies targeting reduced sedentary time (e.g., allowing employees regular desk breaks), or by changing norms surrounding prolonged sitting (e.g., standing meetings).
Results & Conclusions
There are limited data about the minimal amount of SB change required to produce meaningful health benefits. In addition to developing relevant scientific and public health definitions of SB, it is important to further delineate the scope of health and quality of life outcomes associated with reduced SB across the life course, and clarify what behavioral alternatives to SB can be used to optimize health gains. SB interventions will benefit from having more clarity about the potential physiological and behavioral synergies with current PA recommendations, developing multi-level interventions aimed at reducing SB across all life phases and contexts, harnessing relevant and effective strategies to extend the reach of interventions to all sectors of society, as well as applying state-of-the-science adaptive designs and methods to accelerate advances in the science of sedentary behavior interventions.
PMCID: PMC4362870  PMID: 25222818
physical activity; sedentary behavior; sitting; behavior change
10.  The MAT-sf: Identifying Risk for Major Mobility Disability 
The assessment of mobility is essential to both aging research and clinical geriatric practice. A newly developed self-report measure of mobility, the mobility assessment tool-short form (MAT-sf), uses video animations as an innovative method to improve measurement accuracy/precision. The primary aim of the current study was to evaluate whether MAT-sf scores can be used to identify risk for major mobility disability (MMD).
This article is based on data collected from the Lifestyle Interventions and Independence for Elders study and involved 1,574 older adults between the ages of 70–89. The MAT-sf was administered at baseline; MMD, operationalized as failure to complete the 400-m walk ≤ 15 minutes, was evaluated at 6-month intervals across a period of 42 months. The outcome of interest was the first occurrence of MMD or incident MMD.
After controlling for age, sex, clinic site, and treatment arm, baseline MAT-sf scores were found to be effective in identifying risk for MMD (p < .0001). Partitioning the MAT-sf into four groups revealed that persons with scores <40, 40–49, 50–59, and 60+ had failure rates across 42 months of follow-up of 66%, 52%, 35%, and 22%, respectively.
The MAT-sf is a quick and efficient way of identifying older adults at risk for MMD. It could be used to clinically identify older adults that are in need of intervention for MMD and provides a simple means for monitoring the status of patients’ mobility, an important dimension of functional health.
PMCID: PMC4447779  PMID: 25680917
MAT-sf; Mobility disability; LIFE study; Geriatric assessment; Physical function.
11.  In-hospital Mobility Variations across Primary Diagnoses among Older Adults 
To examine the relationship between primary diagnoses and mobility impairment and recovery among hospitalized older adults.
Prospective cohort study.
UF Health Shands Hospital, an 852-bed level I trauma center located in Gainesville, Florida.
18,551 older adults (≥65 years) with 29,148 hospitalizations between 1/2009 and 4/2014.
Incident and discharge mobility impairment and recovery were assessed using the Braden activity subscale score that was recorded by the nursing staff at every shift change–approximately three times per day. Primary diagnosis ICD-9 codes were used as predictors and re-categorized by using the Agency for Health Care Research and Quality Clinical Classification Software.
Out of the 15,498 hospital records where the patient was initially observed to “walk frequently”, 3,186 (20.6%) developed incident mobility impairment (chair-fast or bedfast). Primary diagnoses with a surgical or invasive procedure were the most prevalent (77.2 %) among the hospital observations with incident mobility impairment; otherwise primary diagnoses without surgery were much more associated with discharge mobility impairment (59%). The highest incidence of mobility impairment occurred in patients with heart valve disorders and aortic and peripheral/visceral artery aneurysms (6.24 and 6.05 events per 30 person-days, respectively); septicemia showed the highest incidence rate for mobility limitation at discharge (0.94 events per 30 person-days). Mobility impairment was observed in 13,650 (46.8% of total) records at admission and 5,930 (43.44%) were observed to recover to a state of walking occasionally or frequently. Osteoarthritis and cancer of gastrointestinal organs/peritoneum had the highest incidence rate for mobility recovery (7.68 and 5.63 events per 30 person-days respectively).
Approximately 1 out of 5 patients who were mobile at admission became significantly impaired during hospitalization. However, about half (43.4%) of patients observed to have mobility impairment at admission recovered during hospitalization. Conditions most associated with mobility impairment and recovery are varied, but older patients hospitalized for septicemia and cardiovascular diseases with surgery (heart valve disorders and aortic/peripheral/visceral artery aneurysms) appear to be at most risk for incident mobility impairment that did not recover at discharge.
PMCID: PMC4842101  PMID: 26971132
hospitalization; disability; mobility; aging; comorbidity
12.  Diving Below the Surface of Progressive Disability: Considering Compensatory Strategies as Evidence of Sub-Clinical Disability 
To provide a comprehensive review regarding the role of activity and participation compensations within the disablement process, identify directions for future research, and discuss the implications of compensation pertaining to public health initiatives aimed at preventing and reversing disability.
This article evaluated how using compensatory strategies to cope with functional deficits reveals important transitions within the disablement process and signifies a unique opportunity to identify early declines in function.
Previous research suggests that (a) adopting compensatory strategies to maintain activity/participation is strongly associated with functional decline and disease severity and significantly predicts the onset of limitations/restrictions; (b) compensation can be reliably quantified; and (c) contextual knowledge about how individuals adapt to functional decline can be used to describe transitions in the disablement process.
Characterizing subtle adaptations prior to the onset of activity limitations and participation restrictions will not only aid in understanding the complex disablement process but also help inform social services and future prevention strategies. Overall, this article integrates the concept of compensation into the current model of disability and proposes a framework for identifying and interpreting compensatory behavior.
PMCID: PMC3968860  PMID: 24170713
Preclinical disability; Compensation; ICF; Subclinical disability.
13.  Effectiveness of blood flow restricted exercise compared with standard exercise in patients with recurrent low back pain: study protocol for a randomized controlled trial 
Trials  2016;17:81.
Low back pain is a highly prevalent condition in the United States and has a staggeringly negative impact on society in terms of expenses and disability. It has previously been suggested that rehabilitation strategies for persons with recurrent low back pain should be directed to the medial back muscles as these muscles provide functional support of the lumbar region. However, many individuals with low back pain cannot safely and effectively induce trunk muscle adaptation using traditional high-load resistance exercise, and no viable low-load protocols to induce trunk extensor muscle adaptation exist. Herein, we present the study protocol for a randomized controlled trial that will investigate the “cross-transfer” of effects of a novel exercise modality, blood flow restricted exercise, on cross-sectional area (primary outcome), strength and endurance (secondary outcomes) of trunk extensor muscles, as well as the pain, disability, and rate of recurrence of low back pain (tertiary outcomes).
Methods and study design
This is a single-blinded, single-site, randomized controlled trial. A minimum of 32 (and up to 40) subjects aged 18 to 50 years with recurrent low back pain and poor trunk extensor muscle endurance will be recruited, enrolled and randomized. After completion of baseline assessments, participants will be randomized in a 1:1 ratio to receive a 10-week resistance exercise training program with blood flow restriction (BFR exercise group) or without blood flow restriction (control exercise group). Repeat assessments will be taken immediately post intervention and at 12 weeks after the completion of the exercise program. Furthermore, once every 4 weeks during a 36-week follow-up period, participants will be asked to rate their perceived disability and back pain over the past 14 days.
This study will examine the potential for blood flow restricted exercise applied to appendicular muscles to result in a “cross-transfer” of therapeutic effect to the lumbar musculature in individuals with low back pain. The results of this study will provide important insights into the effectiveness of this novel exercise modality, which could potentially provide the foundation for a cost-effective and easy-to-implement rehabilitation strategy to induce muscle adaptation in the absence of high mechanical and compressive loading on the spine.
Trial registration
This trial is registered with (registration number: NCT02308189, date of registration: 2 December 2014).
PMCID: PMC4751635  PMID: 26867541
Low back pain; Blood flow restriction; KAATSU; Trunk extensor; Muscle; Strength; Endurance; Exercise
14.  A Physical Activity Intervention to Treat the Frailty Syndrome in Older Persons—Results From the LIFE-P Study 
The frailty syndrome is as a well-established condition of risk for disability. Aim of the study is to explore whether a physical activity (PA) intervention can reduce prevalence and severity of frailty in a community-dwelling elders at risk of disability.
Exploratory analyses from the Lifestyle Interventions and Independence for Elders pilot, a randomized controlled trial enrolling 424 community-dwelling persons (mean age=76.8 years) with sedentary lifestyle and at risk of mobility disability. Participants were randomized to a 12-month PA intervention versus a successful aging education group. The frailty phenotype (ie, ≥3 of the following defining criteria: involuntary weight loss, exhaustion, sedentary behavior, slow gait speed, poor handgrip strength) was measured at baseline, 6 months, and 12 months. Repeated measures generalized linear models were conducted.
A significant (p = .01) difference in frailty prevalence was observed at 12 months in the PA intervention group (10.0%; 95% confidence interval = 6.5%, 15.1%), relative to the successful aging group (19.1%; 95% confidence interval = 13.9%,15.6%). Over follow-up, in comparison to successful aging participants, the mean number of frailty criteria in the PA group was notably reduced for younger subjects, blacks, participants with frailty, and those with multimorbidity. Among the frailty criteria, the sedentary behavior was the one most affected by the intervention.
Regular PA may reduce frailty, especially in individuals at higher risk of disability. Future studies should be aimed at testing the possible benefits produced by multidomain interventions on frailty.
PMCID: PMC4311184  PMID: 25387728
Frailty; Physical activity; Physical function; Successful aging; Clinical trials.
15.  Modifying effect of obesity on the association between sitting time and incident diabetes in post-menopausal women 
Obesity (Silver Spring, Md.)  2013;22(4):1133-1141.
To evaluate the association between self-reported daily sitting time and the incidence of type II diabetes in a cohort of postmenopausal women.
Design and Methods
Women (N = 88,829) without diagnosed diabetes reported the number of hours spent sitting over a typical day. Incident cases of diabetes were identified annually by self-reported initiation of using oral medications or insulin for diabetes over 14.4 years follow-up.
Each hour of sitting time was positively associated with increased risk of diabetes (Risk ratio (RR): 1.05; 95% confidence interval (CI): 1.02–1.08]. However, sitting time was only positively associated with incident diabetes in obese women. Obese women reporting sitting 8–11 (RR: 1.08; 95% CI 1.0–1.1), 12–15 (OR: 1.13; 95% CI 1.0–1.2), and ≥16 hours (OR: 1.25; 95% CI 1.0–1.5) hours per day had an increased risk of diabetes compared to women sitting ≤ 7 hours per day. These associations were adjusted for demographics, health conditions, behaviors (smoking, diet and alcohol intake) and family history of diabetes. Time performing moderate to vigorous intensity physical activity did not modify these associations.
Time spent sitting was independently associated with increased risk of diabetes diagnosis among obese women— a population already at high risk of the disease.
PMCID: PMC3968183  PMID: 24123945
sedentary; glucose control; overweight; glycemia
16.  Activity-Related Energy Expenditure in Older Adults: A Call for More Research 
The purpose of this paper is to 1) provide an overview of the science of physical activity-related energy expenditure in older adults (65+ years); 2) offer suggestions for future research and guidelines for how scientists should be reporting their results in this area; and 3) present strategies for making this data more accessible to the lay person. This paper is meant to serve as a preliminary blueprint for future empirical work in the area of energy expenditure in older adults as well as translational efforts to make this data useful and accurate for older adults. This document is based upon deliberations of experts involved in the Strategic Health Initiative on Aging (SHI-A) Committee of the American College of Sports Medicine (ACSM). The paper is designed to reach a broad audience who might not be familiar with the complexities of assessing energy expenditure, especially in older adults.
PMCID: PMC4188802  PMID: 24714651
Physical activity; RMR; oxygen uptake; translation; kilocalories; MET
17.  Cross-sectional and longitudinal risk of physical impairment in a cohort of postmenopausal women who experience physical and verbal abuse 
BMC Women's Health  2015;15:98.
Exposure to interpersonal violence, namely verbal and physical abuse, is a highly prevalent threat to women’s health and well-being. Among older, post-menopausal women, several researchers have characterized a possible bi-directional relationship of abuse exposure and diminished physical functioning. However, studies that prospectively examine the relationship between interpersonal abuse exposure and physical functioning across multiple years of observation are lacking. To address this literature gap, we prospectively evaluate the association between abuse exposure and physical functioning in a large, national cohort of post-menopausal women across 12 years of follow-up observation.
Multivariable logistic regression was used to measure the adjusted association between experiencing abuse and physical function score at baseline in 154,902 Women’s Health Initiative (WHI) participants. Multilevel modeling, where the trajectories of decline in physical function were modeled as a function of time-varying abuse exposure, was used to evaluate the contribution of abuse to trajectories of physical function scores over time.
Abuse was prevalent among WHI participants, with 11 % of our study population reporting baseline exposure. Verbal abuse was the most commonly reported abuse type (10 %), followed by combined physical and verbal abuse (1 %), followed by physical abuse in the absence of verbal abuse (0.2 %). Abuse exposure (all types) was associated with diminished physical functioning, with women exposed to combined physical and verbal abuse presenting baseline physical functioning scores consistent with non-abused women 20 years senior. Results did not reveal a differential rate of decline over time in physical functioning based on abuse exposure.
Taken together, our findings suggest a need for increased awareness of the prevalence of abuse exposure among postmenopausal women; they also underscore the importance of clinician’s vigilance in their efforts toward the prevention, early detection and effective intervention with abuse exposure, including verbal abuse exposure, in post-menopausal women. Given our findings related to abuse exposure and women’s diminished physical functioning at WHI baseline, our work illuminates a need for further study, particularly the investigation of this association in younger, pre-menopausal women so that the temporal ordering if this relationship may be better understood.
PMCID: PMC4641397  PMID: 26554450
Violence; Women; Physical function; WHI; Disability
18.  Safety and metabolic outcomes of resveratrol supplementation in older adults: results of a twelve-week, placebo-controlled pilot study 
Experimental gerontology  2014;0:181-187.
Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73 ± 7 years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300 mg/day), and (3) high dose resveratrol (1000 mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90 days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps < 0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300 mg/day and 1000 mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials.
PMCID: PMC4149922  PMID: 24866496
Resveratrol; Safety; Metabolism; Glucose; Blood pressure
19.  Age-related Differences in Lower Extremity Tissue Compartments and Associations with Physical Function in Older Adults 
Experimental gerontology  2011;47(1):38-44.
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.
PMCID: PMC3245356  PMID: 22015325
Aging; Sarcopenia; Older Adults; Disability; SPPB; IMAT
20.  Dynapenia and Aging: An Update 
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.
PMCID: PMC3260480  PMID: 21444359
Strength; Weakness; Atrophy; Function; Disability
21.  Respiratory Impairment and Dyspnea and Their Associations With Physical Inactivity and Mobility in Sedentary Community-Dwelling Older Persons 
To evaluate the prevalence of respiratory impairment and dyspnea, and their associations with objectively-measured physical inactivity and performance-based mobility in sedentary older persons.
Lifestyle Interventions and Independence in Elder (LIFE) Study.
1635 community-dwelling older persons, mean age 78.9, who reported a sedentary status (<20 minutes/week in the past month of regular physical activity and <125 minutes/week of moderate physical activity).
Respiratory impairment was defined by a reduced ventilatory capacity (forced expiratory volume in 1-second < lower limit of normal [LLN]) and respiratory muscle weakness (maximal inspiratory pressure
Prevalence rates of reduced ventilatory capacity, respiratory muscle weakness, and dyspnea were 17.7%, 14.7%, and 31.6%, and of moderate-to-severe mobility impairment and slow gait speed were 44.7% and 43.6%, respectively. Significant associations were found between reduced ventilatory capacity and slow gait speed (adjusted odds ratio [95% confidence interval]: 1.41 [1.03, 1.92]), respiratory muscle weakness and moderate-to-severe mobility impairment (1.42 [1.03, 1.95]), and dyspnea with high sedentary time and slow gait speed (1.98 [1.28, 3.06] and 1.70 [1.22, 2.38], respectively).
Among sedentary older persons, respiratory impairment and dyspnea are prevalent and associated with objectively-measured physical inactivity or decreased performance-based mobility. Because they are modifiable, respiratory impairment and dyspnea should be considered in the evaluation of sedentary older persons.
PMCID: PMC3989438  PMID: 24635756
FEV1; respiratory muscle weakness; dyspnea; sedentary; mobility
Data are sparse regarding the impacts of habitual physical activity (PA) and sedentary behavior on cardiovascular (CV) risk in older adults with mobility limitations.
Methods and Results
This study examined the baseline, cross‐sectional association between CV risk and objectively measured PA among participants in the Lifestyle Interventions and Independence for Elders (LIFE) study. The relationship between accelerometry measures and predicted 10‐year Hard Coronary Heart Disease (HCHD) risk was modeled by using linear regression, stratified according to CVD history. Participants (n=1170, 79±5 years) spent 642±111 min/day in sedentary behavior (ie, <100 accelerometry counts/min). They also spent 138±43 min/day engaging in PA registering 100 to 499 accelerometry counts/min and 54±37 min/day engaging in PA ≥500 counts/min. Each minute per day spent being sedentary was associated with increased HCHD risk among both those with (0.04%, 95% CI 0.02% to 0.05%) and those without (0.03%, 95% CI 0.02% to 0.03%) CVD. The time spent engaging in activities 100 to 499 as well as ≥500 counts/min was associated with decreased risk among both those with and without CVD (P<0.05). The mean number of counts per minute of daily PA was not significantly associated with HCHD risk in any model (P>0.05). However, a significant interaction was observed between sex and count frequency (P=0.036) for those without CVD, as counts per minute was related to HCHD risk in women (β=−0.94, −1.48 to −0.41; P<0.001) but not in men (β=−0.14, −0.59 to 0.88; P=0.704).
Daily time spent being sedentary is positively associated with predicted 10‐year HCHD risk among mobility‐limited older adults. Duration, but not intensity (ie, mean counts/min), of daily PA is inversely associated with HCHD risk score in this population—although the association for intensity may be sex specific among persons without CVD.
Clinical Trial Registration
URL: Unique identifier: NCT01072500
PMCID: PMC4345863  PMID: 25696062
accelerometry; aging; CVD; Framingham; physical activity
JAMA internal medicine  2014;174(1):98-106.
The impact of obesity on late-age survival without disease or disability in women is unknown.
To investigate if higher baseline body mass index and waist circumference affects women’s survival to age 85 years without major chronic disease (coronary disease, stroke, cancer, diabetes, or hip fracture) and mobility disability.
Design, Setting, Participants
Examination of 36,611 women from the Women’s Health Initiative who could have reached age 85 years or older if they survived to the last outcomes evaluation on September 17, 2012. Recruitment was from 40 US Clinical Centers from October 1993–December 1998. Multinomial logistic regression models were used to estimate odds ratios and 95% confidence intervals for the association of baseline body mass index and waist circumference with the outcomes, adjusting for demographic, behavioral, and health characteristics.
Main Outcome Measures
Mutually-exclusive classifications: 1) survived without major chronic disease and without mobility disability (“healthy”); 2) survived with ≥1 major chronic disease at baseline, but without new disease or disability (“prevalent diseased”); 3) survived and developed ≥1 major chronic disease but not disability during study follow-up (“incident diseased”); 4) survived and developed mobility disability with or without disease (“disabled”); and 5) did not survive (“died”).
Mean (SD) baseline age was 72.4 (3.0) years (range: 66–81). The distribution of women classified as healthy, prevalent diseased, incident diseased, disabled, and died was 19%, 15%, 23%, 18%, and 25%, respectively. Compared to normal-weight women, underweight and obese women were more likely to die before age 85 years. Overweight and obese women had higher risks of incident disease and mobility disability. Disability risks were striking. Relative to normal-weight women, adjusted odds ratios (95% confidence intervals) of mobility disability was 1.6 (1.5–1.8) for overweight women and 3.2 (2.9–3.6), 6.6 (5.4–8.1), and 6.7 (4.8–9.2), for class I, II, and III obesity, respectively. Waist circumference >88 centimeters was also associated with higher risk of earlier death, incident disease, and mobility disability.
Overall and abdominal obesity were important and potentially modifiable factors associated with dying or developing mobility disability and major chronic disease before age 85 years in older women.
PMCID: PMC3963496  PMID: 24217806
Accumulating evidence suggests that both dietary restriction and exercise (DR + E) should be incorporated in weight loss interventions to treat obese, older adults. However, more information is needed on the effects to lower extremity tissue composition—an important consideration for preserving mobility in older adults.
Twenty-seven sedentary women (body mass index: 36.3±5.4kg/m2; age: 63.6±5.6 yrs) were randomly assigned to 6 months of DR + E or a health education control group. Thigh and calf muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) size were determined using magnetic resonance imaging. Physical function was measured using a long-distance corridor walk and knee extension strength.
Compared with control, DR + E significantly reduced body mass (-6.6±3.7kg vs control: -0.05±3.5kg; p < .01). Thigh and calf muscle volumes responded similarly between groups. Within the DR + E group, adipose tissue was reduced more in the thigh than in the calf (p < .04). Knee extension strength was unaltered by DR + E, but a trend toward increased walking speed was observed in the DR + E group (p = .09). Post hoc analyses showed that reductions in SAT and IMAT within the calf, but not the thigh, were associated with faster walking speed achieved with DR + E (SAT: r = -0.62; p = .01; IMAT: r = -0.62; p = .01).
DR + E preserved lower extremity muscle size and function and reduced regional lower extremity adipose tissue. Although the magnitude of reduction in adipose tissue was greater in the thigh than the calf region, post hoc analyses demonstrated that reductions in calf SAT and IMAT were associated with positive adaptations in physical function.
PMCID: PMC4158399  PMID: 23682155
Body composition; Weight loss; Obesity; Aging; Disability.
Age is associated with reductions in surface area and cortical thickness, particularly in prefrontal regions. There is also evidence of greater thickness in some regions at older ages. Non-linear age effects in some studies suggest that age may continue to impact brain structure in later decades of life, but relatively few studies have examined the impact of age on brain structure within middle-aged to older adults. We investigated age differences in prefrontal surface area and cortical thickness in healthy adults between the ages of 51 and 81 years. Participants received a structural 3-Tesla magnetic resonance imaging scan. Based on a priori hypotheses, primary analyses focused on surface area and cortical thickness in the dorsolateral prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex. We also performed exploratory vertex-wise analyses of surface area and cortical thickness across the entire cortex. We found that older age was associated with smaller surface area in the dorsolateral prefrontal and orbitofrontal cortices but greater cortical thickness in the dorsolateral prefrontal and anterior cingulate cortices. Vertex-wise analyses revealed smaller surface area in primarily frontal regions at older ages, but no age effects were found for cortical thickness. Results suggest age is associated with reduced surface area but greater cortical thickness in prefrontal regions during later decades of life, and highlight the differential effects age has on regional surface area and cortical thickness.
PMCID: PMC4717301  PMID: 26834623
adult age differences; cortical thinning; volumetrics; aging; MRI

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