Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Background: Direct assessment of skeletal muscle mass in older adults is clinically challenging. Relationships between lean mass and late-life outcomes have been inconsistent. The D3-creatine dilution method provides a direct assessment of muscle mass. Methods: Muscle mass was assessed by D3-creatine (D3Cr) dilution in 1,382 men (mean age, 84.2 yrs). Participants completed the Short Physical Performance Battery (SPPB); usual walking speed (6 meters); and DXA lean mass...

Investigating the role of nutrition on cognitive health is challenging. Human brain tissue is inaccessible in living humans and is often limited in deceased individuals. Therefore, biomarkers of brain nutrient levels are of interest. The objective of this study was to characterize the relationships between levels of fat-soluble nutrients in serum and matched brain tissues from the frontal and temporal cortices of participants in the Georgia Centenarian Study (n = 47). After adjusting for sex, race, cognitive status (global deterioration scale), body mass index, and presence of hypertension and/or diabetes, there was a significant relationship (p < 0...

There is strong evidence that obesity has deleterious effects on cognitive function of older adults. Previous preclinical studies demonstrate that obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood brain barrier disruption, promoting neuroinflammation and oxidative stress. To test the hypothesis that synergistic effects of obesity and aging on inflammatory processes exert deleterious effects on hippocampal function, young and aged C57BL/6 mice were rendered obese by chronic feeding of a high fat diet followed by assessment of learning and memory function, measurement of hippocampal long-term potentiation (LTP), assessment of changes in hippocampal expression of genes relevant for synaptic function and determination of synaptic density...

Older adults suffer a disproportionate burden of influenza-related morbidity and mortality typically attributed to defects in the aging immune system collectively known as immunosenescence. While the age-related decline in the adaptive immune system has been well characterized, little is known about how aging affects the principal site of influenza infection - the nasal epithelium. In human nasal epithelial cell cultures (hNECs) from older adults, we found similar or increased levels of cytokines during influenza infection compared with hNECs from younger individuals...

Impaired metabolism may play a role in the development and lethality of prostate cancer, yet a comprehensive analysis of the interrelationships appears lacking. We measured 625 metabolites using ultrahigh performance LC/MS-GC/MS of prediagnostic serum from 197 prostate cancer cases in the ATBC Study (ages at diagnosis, 55-86 years). Cox proportional hazards models estimated associations between circulating metabolites and prostate cancer mortality for 1-standard deviation (SD) differences (log-metabolite scale), adjusted for age, year of diagnosis, and disease stage...

Background: Lifestyle interventions to reduce weight and increase activity may preserve higher-order cognitive abilities in overweight/obese adults with type 2 diabetes (T2D). Methods: Adults (N=5,084) with T2D who enrolled in a randomized clinical trial of a 10-year intensive lifestyle intervention (ILI) compared with diabetes support and education were queried at baseline and repeatedly during follow-up for complaints about difficulties in memory, problem-solving, and decision-making abilities...

We examined the relationship between serially measured, novel serum biomarkers and a measure of cognitive functioning in older adults. We assayed stored serum samples from two Fels Longitudinal Study visits in N=100 adult participants (visit 1 ages 59.3 + 8.5 years; 53% female), and Montreal Cognitive Assessment (MoCA) scores also assessed at the second visit. Assays included acylcarnitines, amino acids, and 2-hydroxybutyric acid (b-HBA). Cross-sectional correlations between acyclarnitines and amino acids and MoCA were identified...

Background: Structural and functional brain imaging methods have identified age-related changes in brain structures involved in gait control. This cross-sectional study aims to investigate gray matter networks associated with gait control in aging using structural covariance analysis. Methods: Walking speed were measured in 326 non-demented older community-dwellers (age 71.3±4.5; 41.7% female) under three different walking conditions: normal walking and two challenging tasks: motor (i...

Background: Chronically elevated interleukin-6 (IL-6) levels contribute to fatigue and functional decline via multiple pathways that often lead to frailty. Lesser known is the contribution of IL-6 to fatigue in relation to a standardized workload (fatigability), a precursor to functional decline. Therefore, the purpose of this study was to examine the longitudinal relationship between IL-6 and fatigability. Methods: 985 participants from the Baltimore Longitudinal Study of Aging (mean age: 70+/-10 years) were evaluated every 1-4 years...

Pulmonary hypertension (PH) is a disease of women (female-to-male ratio 4:1), and is associated with cardiac and skeletal muscle dysfunction. Herein, the activation of a new estrogen receptor (GPER) by the agonist G1 was evaluated in oophorectomized rats with monocrotaline (MCT)-induced PH. Depletion of estrogen was induced by bilateral oophorectomy (OVX) in Wistar rats. Experimental groups included SHAM or OVX rats that received a single intraperitoneal injection of MCT (60 mg/kg) for PH induction. Animals received s...

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A frailty index based on clinical deficit accumulation (FI-Clinical) quantifies frailty in aging mice. We aimed to develop a laboratory test-based murine FI tool (FI-Lab) and to investigate the effects of age and sex on FI-Lab scores, FI-Clinical scores and the combination (FI-Combined), as well as to explore links between frailty and inflammation. Studies used older (17 & 23-months) C57BL/6 mice of both sexes. We developed an FI-Lab (blood pressure, blood chemistry, echocardiography) based on deviation from reference values in younger adults (12 months), which showed similar characteristics to a human FI-Lab tool...

Background: The purpose of this study was to examine the association between secondary task involvement and risk of crash and near-crash involvement among older drivers using naturalistic driving data. Methods: Data from drivers aged ≥70 years in the Strategic Highway Research Program (SHRP2) Naturalistic Driving Study database was utilized. The personal vehicle of study participants was equipped with four video cameras enabling recording of the driver and the road environment...

Background: Gait speed is an important measure of lower extremity physical performance in older adults and is predictive of disability and mortality. The biological pathways involved in the decline of lower extremity physical performance are not well understood. We used a targeted metabolomics approach to identify plasma metabolites predictive of change in gait speed over time. Methods: Gait speed was measured at baseline and over median follow-up of 50.5 months in 504 adults, aged ≥50 years, who had two or more study visits in the Baltimore Longitudinal Study of Aging (BLSA)...

Background: Low dual-task gait performance (the slowing of gait speed while performing a demanding cognitive task) is associated with low cognitive performance and an increased risk of progression to dementia in older adults with mild cognitive impairment. However, the reason for this remains unclear. This study aimed to examine the relationship between dual-task cost and regional brain volume, focusing on the hippocampus, parahippocampal gyrus, entorhinal cortex, and motor and lateral frontal cortices in older adults with mild cognitive impairment...

Carcinogenesis is frequently linked to genetic background, however, exposure to environmental risk factors has gained attention as the etiologic agent for several types of cancer, including prostate. The intrauterine microenvironment has been described as a preponderant factor for offspring health; and maternal exposure to insult has been linked to chronic disease in older offspring. Using a model of maternal exposure to low protein diet (LPD; 6% protein), we demonstrated that impairment of offspring rat prostatic growth on postnatal day (PND) 21 was associated with prostate carcinogenesis in older offspring (PND 540)...

Centenarians represent a unique cohort to study the genetic basis for longevity and factors determining the risk of neurodegenerative disorders, including Alzheimer's disease (AD). The estimated genetic contribution to longevity is highest in centenarians and supercententenarians, but few genetic variants have been shown to clearly impact this phenotype. While the genetic risk for AD and other dementias is now well understood, the frequency of known dementia risk variants in centenarians is not fully characterized...

Background: Essential amino acids (EAA) and aerobic exercise (AE) acutely and independently stimulate skeletal muscle protein anabolism in older adults. Objective: In this Phase 1, double blind, placebo controlled, randomized clinical trial, we determined if chronic EAA supplementation, AE training, or a combination of the two interventions could improve muscle mass and function by stimulating muscle protein synthesis. Methods: We phone screened 971, enrolled 109, and randomized 50 independent, low-active, non-frail, non-diabetic older adults (age 72±1 yrs)...

Alveolar sacs are primarily responsible for gas exchange in the human respiratory system and lose their functionality with aging. Three-dimensional (3D) models of young and old human alveolar sacs were constructed and fluid-solid interaction (FSI) was employed to investigate the contribution of age-related changes to decline in alveolar sacs function under mechanical ventilation (MV). Simulations results illustrated that compliance and pressure reduced in the alveolar sacs of the elderly, and they have to work harder to breathe...

Background: We studied the combined effects of cognitive performance and lower extremity function on self-reported walking modifications and walking difficulty, and on self-reported walking difficulty incidence over a two-year follow-up. Methods: A total of 848 community-dwelling older people aged 75-90 years participated at baseline, 816 at the one-year follow-up, and 761 at the two-year follow-up. Baseline lower extremity function was measured with the Short Physical Performance Battery (<10 vs...