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While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Exercise provides a robust physiological stimulus that evokes cross-talk among multiple tissues that when repeated regularly (i.e., training) improves physiological capacity, benefits numerous organ systems, and decreases the risk for premature mortality. However, a gap remains in identifying the detailed molecular signals induced by exercise that benefits health and prevents disease. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to address this gap and generate a molecular map of exercise. Preclinical and clinical studies will examine the systemic effects of endurance and resistance exercise across a range of ages and fitness levels by molecular probing of multiple tissues before and after acute and chronic exercise. From this multi-omic and bioinformatic analysis, a molecular map of exercise will be established. Altogether, MoTrPAC will provide a public database that is expected to enhance our understanding of the health benefits of exercise and to provide insight into how physical activity mitigates disease.

Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18–70 yr, n = 140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. FMD declined with age with a breakpoint and steeper decline occurring at 47 yr of age. Thereafter, age was independently associated with lower FMD (B = −0.13, P < 0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter (B = 0.10, P < 0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle-stimulating hormone (abind = 0.051, P = 0.01) and progesterone (abind = 0.513, P < 0.001) but not estradiol (abind = −0.004, P = 0.08). No mediation was present for cfPWV. Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 yr old, respectively, 3 to 4 yr before the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle-stimulating hormone and progesterone, but not declining estradiol. NEW & NOTEWORTHY: We demonstrate that the age at which endothelial function declines and aortic stiffness increases in healthy women is 47 and 48, respectively. The inflection point in flow-mediated dilation (FMD) is 6 yr earlier than previously reported, and the association between age and FMD was mediated by follicle-stimulating hormone (FSH) and progesterone (P4) but not estradiol (E2). [ABSTRACT FROM AUTHOR]

In cardiovascular research, sex and gender have not typically been considered in research design and reporting until recently. This has resulted in clinical research findings from which not only all women, but also gender-diverse individuals have been excluded. The resulting dearth of data has led to a lack of sex- and gender-specific clinical guidelines and raises serious questions about evidence-based care. Basic research has also excluded considerations of sex. Including sex and/or gender as research variables not only has the potential to improve the health of society overall now, but it also provides a foundation of knowledge on which to build future advances. The goal of this guidelines article is to provide advice on best practices to include sex and gender considerations in study design, as well as data collection, analysis, and interpretation to optimally establish rigor and reproducibility needed to inform clinical decision-making and improve outcomes. In cardiovascular physiology, incorporating sex and gender is a necessary component when optimally designing and executing research plans. The guidelines serve as the first guidance on how to include sex and gender in cardiovascular research. We provide here a beginning path toward achieving this goal and improve the ability of the research community to interpret results through a sex and gender lens to enable comparison across studies and laboratories, resulting in better health for all. [ABSTRACT FROM AUTHOR]

Mechanisms underlying sex differences in brain aging remain unclear but may relate to changes in cerebral pulsatile blood flow. Sex differences in the stiffening of the large arteries and expansion of pulse pressure with age may accelerate changes in pulsatile (i.e., discontinuous) blood flow in the brain that contribute to brain health. The purpose of this cross-sectional, secondary analysis was to examine sex differences in age-associated changes in large artery (aorta and carotid) stiffness, carotid pulse pressure, and cerebral pulsatility in 206 men and 217 women between 18 and 72 yr of age. Outcomes included aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] and carotid pulse pressure via tonometry, carotid b-stiffness via ultrasound, and middle cerebral artery (MCA) pulsatility index via transcranial Doppler. Regression analyses revealed a significant age-by-sex interaction, with women exhibiting a slower rate of change compared with men for cfPWV (β = -0.21, P = 0.04), and greater rate of change for carotid stiffness (β = 0.27, P = 0.02), carotid pulse pressure (β = 0.98, P < 0.001), and MCA pulsatility index (β = 0.49, P = 0.002) after adjustment for covariates. The significant age-by-sex interaction for MCA pulsatility was abolished after further adjustment for carotid pulse pressure. Women exhibit accelerated increases in cerebral pulsatility during midlife, likely driven by exaggerated increases in carotid stiffness and pulse pressure compared with men. These data suggest that there are disproportionate increases in cerebral pulsatility in women during midlife that could contribute to accelerated brain aging compared with men. [ABSTRACT FROM AUTHOR]

Compared eating behaviors and alcohol drinking habits between female varsity college athletes and female controls (non-athletes). Data from a student survey indicated that self-reported problem drinking and eating behaviors existed in both groups at similar rates. There did not appear to be a significant relationship between self-reported alcohol use and eating disorders. (SM)

Endothelial function (brachial artery flow-mediated dilation [FMD]) is reduced in estrogen-deficient postmenopausal women, mediated, in part, by reduced nitric oxide (NO) bioavailability, secondary to tetrahydrobiopterin (BH4) deficiency and oxidative stress. FMD is increased, but not fully restored, in postmenopausal women after acute intravenous vitamin C (VITC; superoxide scavenger) or oral BH4 supplementation. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite. To investigate mechanisms of endothelial dysfunction in women, we assessed the separate and combined effects of VITC and BH4 to determine whether coadministration of VITC + BH4 improves FMD in healthy postmenopausal women (n = 19, 58 ± 5 yr) to premenopausal (n = 14, 36 ± 9 yr) levels, with exploratory testing in perimenopausal women (n = 8, 51 ± 3 yr). FMD was measured during acute intravenous infusions of saline (control) and VITC (∼2–3 g) ∼3 h after a single dose of oral BH4 (KUVAN, 10 mg/kg body wt) or placebo (randomized crossover, separated by ∼1 mo). Under the placebo condition, FMD was reduced in postmenopausal compared with premenopausal women during the saline infusion (5.6 ± 0.7 vs. 11.6 ± 0.9%, P < 0.001) and increased in postmenopausal women during VITC (+3.5 [1.4, 5.6]%, P = 0.001) and acute BH4 (+1.8 [0.37, 3.2]%, P = 0.01) alone. Coadministration of VITC + BH4 increased FMD in postmenopausal women (+3.0 [1.7, 4.3]%, P < 0.001), but FMD remained reduced compared with premenopausal women (P = 0.02). Exploratory analyses revealed that VITC + BH4 did not restore FMD in perimenopausal women to premenopausal levels (P = 0.045). Coadministration of VITC + BH4 does not restore FMD in menopausal women, suggesting that additional mechanisms may be involved. NEW & NOTEWORTHY Endothelial function is reduced across the menopausal stages related to increased oxidative stress associated with estrogen deficiency. In vitro studies demonstrate that coadministration of VITC with BH4 prevents endothelial nitric oxide synthase (eNOS) uncoupling and reductions in NO by peroxynitrite; however, this remains untested in humans. We demonstrate that the coadministration of BH4 + VITC does not restore endothelial function in perimenopausal and postmenopausal women to the level of premenopausal women, suggesting that other mechanisms contribute. [ABSTRACT FROM AUTHOR]

King, G.A., B. Fulkerson, M.J. Evans, K.L. Moreau, J.E. McLaughlin, and D.L. Thompson. Effect of clothing type on validity of air-displacement plethysmography. J. Strength Cond. Res. 20(1):95-102. 2006. The purpose of the study was to evaluate the validity of an air-displacement plethysmography systeta (AP) within the general population, while wearing (1) a racing-type swimsuit ([AP.sub.ss]) and (2) participant's personal undergarments ([AP.sub.UG]), against hydrodensitometry (HW). Fifty women and 50 men were measured for body volume, density, and fat percentage by HW and compared with [AP.sub.ss] and [AP.sub.UG]. For women, [AP.sub.UG] and [AP.sub.ss] were similar, although significant differences (p < 0.001) were observed between [AP.sub.UG] and HW and between [AP.sub.ss] and HW. For men, there was no significant difference between [AP.sub.UG] and HW; however, significant differences (P [less than or equal to] 0.01) were found between [AP.sub.UG] and [AP.sub.ss] and between [AP.sub.ss] and HW. The small discrepancy in measured values between AP and HW are within the measurement error for the instrumentation and these data support the use of AP for determination of body composition in adults across a wide range of body size (body mass index [BMI] 17.7-35.2 kg.[m.sup.-2]) and age (18-57 y). Participants' personal undergarments provide a practical alternative to a spandex swimsuit when measuring body composition by AP in women but not in men. KEY WORDS. body composition, body volume, densitometry, body fat, BOD POD