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Purpose: To investigate the relationship between pacing strategy and performance during uphill and downhill running—specifically, what distribution of energy corresponds to faster race finish times between and among participants. Methods: Eighteen years of race data from a 10.2-mile running race with an uphill first half and a downhill second half were analyzed to identify relationships between pacing and performance. A pacing coefficient (PC), equal to a participant's ascent time divided by finishing time (FT), was used to define each participant's pacing strategy. The American College of Sports Medicine metabolic running equation was used to estimate energy expenditure during the ascent, descent, and total race. Statistical analyses compared participants' PC to their FT and finishing place within their age and gender category. Additionally, FT and finishing place were compared between groups of participants who exhibited similar pacing strategies. Results: PCs were positively associated with faster FTs (r2 =.120, P <.001) and better finishing positions (r2 =.104, P <.001). PCs above.600 were associated with the fastest average FTs and best average finishing position within age and gender categories (all P ≤.047). Conclusions: Participants performed the best when energy expenditure increased no more than 10.4% during the uphill portion compared to their overall average. It is not possible to state that overly aggressive uphill efforts resulted in premature fatigue and thus slower decent times and worse race performance. However, participants should still avoid overly aggressive uphill pacing, as performance was associated with larger PCs. [ABSTRACT FROM AUTHOR]

INTRODUCTION: High-altitude [>2400m (7874ft)] acclimatization has been well studied with physiological adaptations like reductions in body weight and exercise capacity. However, despite the significance of moderate altitude [MA, 1524–2438m (5000–8000ft)], acclimatization at this elevation is not well described. We aimed to investigate differences in mice reared at MA compared to sea level (SL). We hypothesized that MA mice would be smaller and leaner and voluntarily run less than SL mice. METHODS: C57BL/6 mice reared for at least three generations in Laramie, WY [2194m (7198ft), MA], were compared to C57BL/6J mice from Bar Harbor, ME [20m (66ft), SL]. We quantified body composition and exercise outputs as well as cardiopulmonary morphometrics. Subsets of MA and SL mice were analyzed to determine differences in neuronal activation after exercise. RESULTS: When body weight was normalized to tibia length, SL animals weighed 1.30g ⋅ mm-1 while MA mice weighed 1.13g · mm-1. Total fat % and trunk fat % were higher in MA mice with values of 41% and 39%, respectively, compared to SL mice with values of 28% and 26%, respectively. However, no differences were noted in leg fat %. MA animals had higher heart mass (119mg) and lower lung mass (160mg) compared to SL mice heart mass (100mg) and lung mass (177mg). MA mice engaged in about 40% less voluntary wheel-running activity than SL animals. DISCUSSION: Physiological differences are apparent between MA and SL mice, prompting a need to further understand larger scale implications of residence at moderate altitude. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is an enormous public health problem, particularly in older populations. Exercise is the most potent cardioprotective intervention identified to date, with exercise in the juvenile period potentially imparting greater protection, given the plasticity of the developing heart. To test the hypothesis that voluntary wheel running early in life would be cardioprotective later in life when risk for disease is high, we provided male and female juvenile (3 wk old) mice access to a running wheel for 2 wk. Mice then returned to a home cage to age to adulthood (4--6 mo) before exposure to isoproterenol (ISO) to induce cardiac stress. Cardiac function and remodeling were compared with sedentary control mice, sedentary mice exposed to ISO, and mice that exercised in adulthood immediately before ISO. Early in life activity protected against ISO-induced stress as evidenced by attenuated cardiac mass, myocyte size, and fibrosis compared with sedentary mice exposed to ISO. ISO-induced changes in cardiac function were ameliorated in male mice that engaged in wheel running, with ejection fraction and fractional shortening reversed to control values. Adrenergic receptor expression was downregulated in juvenile male runners. This suppression persisted in adulthood following ISO, providing a putative mechanism by which exercise in the young male heart provides resilience to cardiac stress later in life. Together, we show that activity early in life induces persistent cardiac changes that attenuate ISO-induced stress in adulthood. Identification of the mechanisms by which early in life exercise is protective will yield valuable insights into how exercise is medicine across the life course. [ABSTRACT FROM AUTHOR]

The mammalian circadian clock governs physiological, endocrine, and metabolic responses coordinated in a 24-h rhythmic pattern by the suprachiasmatic nucleus (SCN) of the anterior hypothalamus. The SCN also dictates circadian rhythms in peripheral tissues like the kidney. The kidney has several important physiological functions, including removing waste and filtering the blood and regulating fluid volume, blood osmolarity, blood pressure, and Ca2+ metabolism, all of which are under tight control of the molecular/circadian clock. Normal aging has a profound influence on renal function, central and peripheral circadian rhythms, and the sleep-wake cycle. Disrupted circadian rhythms in the kidney as a result of increased age likely contribute to adverse health outcomes such as nocturia, hypertension, and increased risk for stroke, cardiovascular disease, and end organ failure. Regular physical activity improves circadian misalignment in both young and old mammals, although the precise mechanisms for this protection remain poorly described. Recent advances in the heart and skeletal muscle literature suggest that regular endurance exercise entrains peripheral clocks, and we propose that similar beneficial adaptations occur in the kidney through regulation of renal blood flow and fluid balance. [ABSTRACT FROM AUTHOR]

The molecular clock plays key roles in daily physiological functions, development and cancer. Period 2 (PER2) is a repressive element, which inhibits transcription activated by positive clock elements, resulting in diurnal cycling of genes. However, there are gaps in our understanding of the role of the clock in normal development outside of its time-keeping function. Here, we show that PER2 has a noncircadian function that is crucial to mammalian mammary gland development. Virgin Per2-deficient mice, Per2-/-, have underdeveloped glands, containing fewer bifurcations and terminal ducts than glands of wildtype mice. Using a transplantation model, we show that these changes are intrinsic to the gland and further identify changes in cell fate commitment. Per2-/- mouse mammary glands have a dual luminal/basal phenotypic character in cells of the ductal epithelium. We identified colocalization of E-cadherin and keratin 14 in luminal cells. Similar results were demonstrated using MCF10A and shPER2 MCF10A human cell lines. Collectively this study reveals a crucial noncircadian function of PER2 in mammalian mammary gland development, validates the Per2-/- model, and describes a potential role for PER2 in breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Circadian rhythms are responsible for physiological and behavioral processes coordinated in a 24-hour cycle. We investigated whether untimed, long-term voluntary wheel access mitigated circadian disruption and facilitated re-entrainment. Methods: Thirty-four C57Bl/6 J mice (n = 21 males, n = 14 females) were used in this experiment. Long-term exercised (LTEx) mice ran from 3 wks to 12 mo of age. At 12 mo animals were circadian disrupted for 14 d and then re-entrained for 7 d. Long-term sedentary (LTSed) animals were disrupted but had no access to a wheel. Another long-term sedentary group had access to a wheel only during disruption (LTSed+Ex). SubCue dataloggers were used to track internal rhythm of core body temperature (Tb). RNA was extracted from skeletal muscle and RT-qPCR was used to analyze gene expression. Results: Overall, all three experimental groups had an initial entrained period lengths of ~24 h at baseline. There was a main effect of time (p = 0.012), treatment (p = 0.005) and interaction of time x treatment (p = 0.033) from baseline to disruption. A post-hoc analysis within group one-way ANOVAs showed no difference between baseline and disruption period lengths in the LTSed+Ex treatment, yet a difference from baseline to disruption in LTSed and LTEx. Lastly, there is a difference in entrained period lengths between all three treatment groups at the re-entrainment time point (p = 0.026) with a difference in change between disruption and re-entrainment with LTEx being lower than LTSed+Ex. Conclusions: Our results suggest that acute-like exercise during circadian disruption aided in mitigating circadian disruption. When all treatment groups were re-entrained back to a normal rhythm, the LTEx animals that had access to a wheel prior to, during, and after disruption had period lengths closest to baseline values., Competing Interests: Conflict of Interest and Funding Source: This work was supported by 2P20GM103432 and 2P20GM12131006, as well as a graduate student grant from Rocky Mountain American College of Sports Medicine. The authors declare no conflicts of interest., (Copyright © 2025 by the American College of Sports Medicine.)

The developmental origins of health and disease theory suggests that environmental exposures during early life, particularly during prenatal life, can greatly influence health status later in life. Irregular light-dark cycles, such as those experienced during shift work, result in the repeated disruption of circadian rhythms, which negatively impacts physiological and behavioral cycles. The purpose of our study was to assess parameters in the developing mouse embryo and fetus using high frequency ultrasound when exposed to circadian disruption. Pregnant female mice were subjected to a seven-hour advanced circadian disrupted protocol or remained on a normal 12/12 light-dark cycle throughout pregnancy. Significant differences were observed in placental length (p = 0.00016), placental thickness (p = 0.0332), and stomach diameter (p = 0.0186) at E14.5-18.5. These findings suggest that circadian disruption in pregnant dams, mimicking shift work, alters embryonic and fetal development in specific organs in utero ., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

INTRODUCTION: High-altitude [>2400 m (7874 ft)] acclimatization has been well studied with physiological adaptations like reductions in body weight and exercise capacity. However, despite the significance of moderate altitude [MA, 1524-2438 m (5000-8000 ft)], acclimatization at this elevation is not well described. We aimed to investigate differences in mice reared at MA compared to sea level (SL). We hypothesized that MA mice would be smaller and leaner and voluntarily run less than SL mice. METHODS: C57BL/6 mice reared for at least three generations in Laramie, WY [2194 m (7198 ft), MA], were compared to C57BL/6J mice from Bar Harbor, ME [20 m (66 ft), SL]. We quantified body composition and exercise outputs as well as cardiopulmonary morphometrics. Subsets of MA and SL mice were analyzed to determine differences in neuronal activation after exercise. RESULTS: When body weight was normalized to tibia length, SL animals weighed 1.30 g ⋅ mm -1 while MA mice weighed 1.13 g · mm -1 . Total fat % and trunk fat % were higher in MA mice with values of 41% and 39%, respectively, compared to SL mice with values of 28% and 26%, respectively. However, no differences were noted in leg fat %. MA animals had higher heart mass (119 mg) and lower lung mass (160 mg) compared to SL mice heart mass (100 mg) and lung mass (177 mg). MA mice engaged in about 40% less voluntary wheel-running activity than SL animals. DISCUSSION: Physiological differences are apparent between MA and SL mice, prompting a need to further understand larger scale implications of residence at moderate altitude. O'Connor AE, Hatzenbiler DM, Flom LT, Bobadilla A-C, Bruns DR, Schmitt EE. Physiological and morphometric differences in resident moderate-altitude vs. sea-level mice . Aerosp Med Hum Perform. 2023; 94(12):887-893.