The Bone, Exercise, Alendronate, and Caloric Restriction (BEACON) trial design and methods.

Background: Among older adults living with obesity, intentional weight loss (WL) improves prognosis of many comorbidities. However, concomitant decline in bone mineral density (BMD) limits overall benefit of WL by increasing osteoporotic fracture risk. Identification of intervention strategies to maximize body fat loss, while minimizing harm to the musculoskeletal system, is an important area of clinical research.

Gonadal status modulates large elastic artery stiffness in healthy middle-aged and older men.

Hypogonadism is a risk factor for cardiovascular disease (CVD) in men related, in part, to increased oxidative stress. Elevated large artery stiffness and central pulsatile hemodynamics (e.g.

Sex Differences Across the Lifespan: A Focus on Cardiometabolism.

Women's health and sex differences research remain understudied. In 2022, to address the topic of sex differences, the Ludeman Family Center for Women's Health Research (LFCWHR) at the University of Colorado (LudemanCenter.org) held its third National Conference, "Sex Differences Across the Lifespan: A Focus on Metabolism.

Adipogenic differentiation of hematopoietic lineage cells isolated from adipose tissue of humans.

We previously discovered some adipocytes in the major white fat depots of mice and humans arise from bone marrow-derived cells of hematopoietic lineage rather than conventional mesenchymal precursors, termed bone marrow-derived adipocytes (BMDA). Here we aimed to determine if hematopoietic lineage cells isolated from adipose tissue and circulation of humans could undergo adipogenic differentiation thereby establishing an model for studies of BMDA. We hypothesized that hematopoietic lineage cells isolated from adipose tissue, but not circulation, of humans would demonstrate adipogenic potential.

Molecular Transducers of Physical Activity Consortium (MoTrPAC): human studies design and protocol.

Physical activity, including structured exercise, is associated with favorable health-related chronic disease outcomes. Although there is evidence of various molecular pathways that affect these responses, a comprehensive molecular map of these molecular responses to exercise has not been developed. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) is a multicenter study designed to isolate the effects of structured exercise training on the molecular mechanisms underlying the health benefits of exercise and physical activity.

Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.

Loss of ovarian function imparts increased susceptibility to obesity and metabolic disease. These effects are largely attributed to decreased estradiol (E), but the role of increased follicle-stimulating hormone (FSH) in modulating energy balance has not been fully investigated. Previous work that blocked FSH binding to its receptor in mice suggested this hormone may play a part in modulating body weight and energy expenditure after ovariectomy (OVX).

Brown adipose tissue metabolism in women is dependent on ovarian status.

In rodents, loss of estradiol (E) reduces brown adipose tissue (BAT) metabolic activity. Whether E impacts BAT activity in women is not known. BAT oxidative metabolism was measured in premenopausal ( = 27; 35 ± 9 yr; body mass index = 26.

Chronotropic Incompetence During Exercise Testing as a Marker of Autonomic Dysfunction in Individuals with Early Parkinson's Disease.

Background: An attenuated heart rate response to exercise, termed chronotropic incompetence, has been reported in Parkinson's disease (PD). Chronotropic incompetence may be a marker of autonomic dysfunction and a cause of exercise intolerance in early stages of PD.

Objective: To investigate the relationship between chronotropic incompetence, orthostatic blood pressure change (supine - standing), and exercise performance (maximal oxygen consumption, VO2peak) in individuals with early PD within 5 years of diagnosis not on dopaminergic medications.

Bone Structure and Turnover in Postmenopausal Women With Long-Standing Type 1 Diabetes.

Compromised bone structural and mechanical properties are implicated in the increased fracture risk in type 1 diabetes (T1D). We investigated bone structure and turnover by histomorphometry in postmenopausal women with T1D and controls without diabetes using tetracycline double-labeled transiliac bone biopsy. After in vivo tetracycline double labeling, postmenopausal women with T1D of at least 10 years and without diabetes underwent transiliac bone biopsy.

Study in Parkinson's disease of exercise phase 3 (SPARX3): study protocol for a randomized controlled trial.

Background: To date, no medication has slowed the progression of Parkinson's disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disease progression, beyond the well-documented benefit of endurance training on a treadmill for fitness, gait, and functional mobility.

The Bone Biomarker Response to an Acute Bout of Exercise: A Systematic Review with Meta-Analysis.

Background: Circulating biomarkers are often used to investigate the bone response to an acute bout of exercise, but heterogeneity in factors such as study design, quality, selected biomarkers, and exercise and participant characteristics render it difficult to synthesize and evaluate available evidence.

Objective: The aim of this study was to quantify the effects of an acute exercise bout on bone biomarkers, along with the influence of potential moderators such as participant, exercise, and design characteristics, using a systematic review and meta-analytic approach.

Methods: The protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) guidelines and prospectively published.

Age-associated reductions in cardiovagal baroreflex sensitivity are exaggerated in middle-aged and older men with low testosterone.

Aging is associated with reductions in cardiovagal baroreflex sensitivity (cBRS), which increases cardiovascular disease risk. Preclinical data indicate that low testosterone reduces cBRS. We determined whether low testosterone is associated with greater age-associated reductions in cBRS in healthy men.

Hematopoietic Stem Cell-Derived Adipocytes Modulate Adipose Tissue Cellularity, Leptin Production and Insulin Responsiveness in Female Mice.

A subpopulation of adipocytes in the major adipose depots of mice is produced from hematopoietic stem cells rather than mesenchymal progenitors that are the source of conventional white and brown/beige adipocytes. To analyze the impact of hematopoietic stem cell-derived adipocytes (HSCDAs) in the adipose niche we transplanted HSCs in which expression of a diphtheria toxin gene was under the control of the adipocyte-specific adiponectin gene promoter into irradiated wild type recipients. Thus, only adipocytes produced from HSC would be ablated while conventional white and brown adipocytes produced from mesenchymal progenitor cells would be spared.

Bone Turnover Markers After Six Nights of Insufficient Sleep and Subsequent Recovery Sleep in Healthy Men.

Purpose: The goal of this study was to determine the bone turnover marker (BTM) response to insufficient and subsequent recovery sleep, independent of changes in posture, body weight, and physical activity.

Methods: Healthy men (N = 12) who habitually slept 7-9 h/night were admitted to an inpatient sleep laboratory for a baseline 8 h/night sleep opportunity followed by six nights of insufficient sleep (5 h/night). Diet, physical activity, and posture were controlled.

Body composition and cardiometabolic health across the menopause transition.

Every year, 2 million women reach menopause in the United States, and they may spend 40% or more of their life in a postmenopausal state. In the years immediately preceding menopause-known as the menopause transition (or perimenopause)-changes in hormones and body composition increase a woman's overall cardiometabolic risk. In this narrative review, we summarize the changes in weight, body composition, and body fat distribution, as well as the changes in energy intake, energy expenditure, and other cardiometabolic risk factors (lipid profile, glucose metabolism, sleep health, and vascular function), that occur during the menopause transition.

Acute catabolic bone metabolism response to exercise in young and older adults: A narrative review.

Exercise is recommended for cardiometabolic benefits and to preserve or improve bone health, especially for older adults at increased risk of fracture. However, exercise interventions have modest benefits on areal bone mineral density (aBMD), and exercise can lead to bone loss in young athletes under certain conditions. In this narrative review, we discuss evidence for a disruption in calcium homeostasis during exercise that may diminish the skeletal benefits of exercise.

Oxidative Stress and Inflammation Are Associated With Age-Related Endothelial Dysfunction in Men With Low Testosterone.

Context: Vascular aging, including endothelial dysfunction secondary to oxidative stress and inflammation, increases the risk for age-associated cardiovascular disease (CVD). Low testosterone in middle-aged/older men is associated with increased CVD risk.

Objective: We hypothesized that low testosterone contributes to age-associated endothelial dysfunction, related in part to greater oxidative stress and inflammation.

The Effects of Exercise Duration and Intensity on Breast Cancer-Related DNA Methylation: A Randomized Controlled Trial.

Emerging research suggests that one mechanism through which physical activity may decrease cancer risk is through its influence on the methylation of genes associated with cancer. The purpose of the current study was to prospectively test, using a rigorous experimental design, whether aerobic exercise affects DNA methylation in genes associated with breast cancer, as well as whether quantity of exercise completed affects change in DNA methylation in a dose-response manner. 276 women (M age = 37.

Hematopoietic stem cells produce intermediate lineage adipocyte progenitors that simultaneously express both myeloid and mesenchymal lineage markers in adipose tissue.

Some adipocytes are produced from bone marrow hematopoietic stem cells. studies previously indicated that these bone marrow-derived adipocytes (BMDAs) were generated from adipose tissue macrophage (ATM) that lose their hematopoietic markers and acquire mesenchymal markers prior to terminal adipogenic differentiation. Here we interrogated whether this hematopoietic-to-mesenchymal transition drives BMDA production .

The Effects of Exercise on Bone Mineral Density in Men: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

The aim of this systematic review and meta-analysis was to provide an updated analysis, including the use of more robust methods, on the effects of exercise on bone mineral density in men. Randomised Control Trials of > 24 weeks and published in English up to 01/05/20 were retrieved from 3 electronic databases, cross-referencing, and expert review. The primary outcome measures were changes in FN, LS, and lower limb BMD Standardised effect sizes were calculated from each study and pooled using the inverse heterogeneity model.

Maintaining serum ionized calcium during brisk walking attenuates the increase in bone resorption in older adults.

Background: Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and bone resorption, reflected by serum carboxy-terminal collagen crosslinks (CTX). We developed a calcium clamp to prevent the decrease in iCa during exercise, which attenuated increases in PTH and CTX during vigorous cycling in young men. The goal was to determine whether this occurs in older adults during brisk walking.

Bone turnover marker responses to sleep restriction and weekend recovery sleep.

Background: Prior data demonstrated three weeks of sleep restriction and concurrent circadian disruption uncoupled bone turnover markers (BTMs), indicating decreased bone formation and no change or increased bone resorption. The effect of insufficient sleep with or without ad libitum weekend recovery sleep on BTMs is unknown.

Methods: BTMs were measured in stored serum from 20 healthy adults randomized to one of three study groups consisting of a control group (N = 3 men; 9 h/night) or one of two nocturnal sleep restriction groups in an inpatient laboratory environment.

Effects of Estradiol on Immunoglobulin G Glycosylation: Mapping of the Downstream Signaling Mechanism.

Glycans attached to immunoglobulin G (IgG) directly affect this antibody effector functions and regulate inflammation at several levels. The composition of IgG glycome changes significantly with age. In women, the most notable change coincides with the perimenopausal period.

Ibuprofen taken before exercise blunts the IL-6 response in older adults but does not alter bone alkaline phosphatase or c-telopeptide.

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) taken before exercise have been shown to impair bone formation. NSAIDs also suppress inflammatory cytokines, such as interleukin-6 (IL-6), that can have pro-resorptive effects. It is unclear how taking NSAIDs timed around exercise influences inflammatory and bone biomarkers following an acute exercise bout in older adults.