Sex-specific 25-hydroxyvitamin D threshold concentrations for functional outcomes in older adults: PRoject on Optimal VItamin D in Older adults (PROVIDO).

BACKGROUND: Threshold serum 25-hydroxyvitamin D [25(OH)D] concentrations for extraskeletal outcomes are uncertain and could differ from recommendations (20-30 ng/mL) for skeletal health. OBJECTIVES: We aimed to identify and validate sex-specific threshold 25(OH)D concentrations for older adults' physical function. METHODS: Using 5 large prospective, population-based studies-Age, Gene/Environment Susceptibility-Reykjavik (n = 4858, Iceland); Health, Aging, and Body Composition (n = 2494, United States); Invecchiare in Chianti (n = 873, Italy); Osteoporotic Fractures in Men (n = 2301, United States); and Study of Osteoporotic Fractures (n = 5862, United States)-we assessed 16,388 community-dwelling adults (10,376 women, 6012 men) aged ≥65 y. We analyzed 25(OH)D concentrations with the primary outcome (incident slow gait: women <0.8 m/s; men <0.825 m/s) and secondary outcomes (gait speed, incident self-reported mobility, and stair climb impairment) at median 3.0-y follow-up. We identified sex-specific 25(OH)D thresholds that best discriminated incident slow gait using machine learning in training data (2/3 cohort-stratified random sample) and validated using the remaining (validation) data and secondary outcomes. RESULTS: Mean age in the cohorts ranged from 74.4 to 76.5 y in women and from 73.3 to 76.6 y in men. Overall, 1112/6123 women (18.2%) and 494/3937 men (12.5%) experienced incident slow gait, 1098/7011 women (15.7%) and 474/3962 men (12.0%) experienced incident mobility impairment, and 1044/6941 women (15.0%) and 432/3993 men (10.8%) experienced incident stair climb impairment. Slow gait was best discriminated by 25(OH)D <24.0 ng/mL compared with 25(OH)D ≥24.0 ng/mL in women (RR: 1.29; 95% CI: 1.10, 1.50) and 25(OH)D <21.0 ng/mL compared with 25(OH)D ≥21.0 ng/mL in men (RR: 1.43; 95% CI: 1.01, 2.02). Most associations between 25(OH)D and secondary outcomes were modest; estimates were similar between validation and training datasets. CONCLUSIONS: Empirically identified and validated sex-specific threshold 25(OH)D concentrations for physical function for older adults, 24.0 ng/mL for women and 21.0 ng/mL for men, may inform candidate reference concentrations or the design of vitamin D intervention trials.

The Relationship of Lean Body Mass With Aging to the Development of Diabetes.

CONTEXT: Older adults have the greatest burden of diabetes; however, the contribution of age-related muscle loss to its development remains unclear. OBJECTIVE: We assessed the relationship of lean body mass with aging to incident diabetes in community-dwelling adults. DESIGN AND SETTING: We studied participants in the Baltimore Longitudinal Study of Aging with median follow-up of 7 years (range 1-16). Cox proportional hazard models with age as the time scale were used. Time-dependent lean body mass measures were updated at each follow-up visit available. PARTICIPANTS: Participants included 871 men and 984 women without diabetes who had  ≥ 1 assessment of body composition using dual x-ray absorptiometry. MAIN OUTCOMES: Incident diabetes, defined as self-reported history and use of glucose-lowering medications; or fasting plasma glucose ≥ 126 mg/dL and 2-hour oral glucose tolerance test glucose ≥ 200 mg/dL either at the same visit or 2 consecutive visits. RESULTS: The baseline mean [standard deviation] age was 58.9  [17.3] years. Men and women with a higher percentage of total lean body mass had lower fasting and 2-hour glucose levels, and less prediabetes (all P < 0.01). Among men, comparing highest versus lowest quartiles, percentage of total lean body mass (hazard ratio [HR],  0.46; 95% confidence interval, 0.22-0.97), percentage leg lean mass (HR, 0.38; 0.15-0.96), and lean-to-fat mass ratio (HR, 0.39; 0.17-0.89) were inversely associated with incident diabetes after accounting for race and attenuated after adjustment for height and weight. Conversely, absolute total lean body mass was positively associated with incident diabetes among women, with similar trends in men. No associations were observed with muscle strength or quality. CONCLUSIONS: Relatively lower lean body mass with aging is associated with incident diabetes in men and partially related to anthropometrics, but not so in women.

Walking speed decline in older adults is associated with elevated pro-BDNF in plasma extracellular vesicles.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is produced by cleavage of proBDNF, and BDNF and proBDNF may play antagonistic roles in nervous system development, learning, memory and neuronal stress resistance. BDNF and proBDNF are present in blood, but the origin and relative contributions of soluble and extracellular vesicle (EV)-associated levels are unknown. METHODS: In this study we used validated immunoassays to measure proBDNF and BDNF levels in plasma, total plasma EVs and a subpopulation of EVs enriched for neuronal origin (expressing the neuronal marker L1CAM) in 150 Baltimore Longitudinal Study of Aging participants with and without decline in walking speed (reflecting aging-associated motor decline). RESULTS: Levels of BDNF and proBDNF were highest in L1CAM+ EVs. Participants with walking speed decline had higher levels of proBDNF in L1CAM+ EVs compared to non-decliners, but no differences in proBDNF levels in plasma and total EV. CONCLUSIONS: Our findings suggest that levels of proBDNF and BDNF in circulating L1CAM+ EVs might be used as biomarkers for conditions involving altered BDNF signaling.

Basal body temperature as a biomarker of healthy aging.

Scattered evidence indicates that a lower basal body temperature may be associated with prolonged health span, yet few studies have directly evaluated this relationship. We examined cross-sectional and longitudinal associations between early morning oral temperature (95.0-98.6 °F) and usual gait speed, endurance walk performance, fatigability, and grip strength in 762 non-frail men (52 %) and women aged 65-89 years participating in the Baltimore Longitudinal Study of Aging. Since excessive adiposity (body mass index ≥35 kg/m2 or waist-to-height ratio ≥0.62) may alter temperature set point, associations were also examined within adiposity strata. Overall, controlling for age, race, sex, height, exercise, and adiposity, lower temperature was associated with faster gait speed, less time to walk 400 m quickly, and lower perceived exertion following 5-min of walking at 0.67 m/s (all p ≤ 0.02). In the non-adipose (N = 662), these associations were more robust (all p ≤ 0.006). Direction of association was reversed in the adipose (N = 100), but none attained significance (all p > 0.22). Over 2.2 years, basal temperature was not associated with functional change in the overall population or non-adipose. Among the adipose, lower baseline temperature was associated with greater decline in endurance walking performance (p = 0.006). In longitudinal analyses predicting future functional performance, low temperature in the non-adipose was associated with faster gait speed (p = 0.021) and less time to walk 400 m quickly (p = 0.003), whereas in the adipose, lower temperature was associated with slower gait speed (p = 0.05) and more time to walk 400 m (p = 0.008). In older adults, lower basal body temperature appears to be associated with healthy aging in the absence of excessive adiposity.