American journal of physiology. Regulatory, integrative and comparative physiology最新文献

{"title":"Hyperphagia and hepatic lipid storage in ducks: an exploratory experimental model.","authors":"Laura-Lou Zwick, Chaïma Hakkach, Sandra Biasutti, Charlotte Andrieux, Jérôme Roy, Stéphane Panserat, Marianne Houssier","doi":"10.1152/ajpregu.00191.2025","DOIUrl":"10.1152/ajpregu.00191.2025","url":null,"abstract":"<p><p>This study aimed to investigate whether spontaneous hyperphagic behavior can be induced in mule ducks through a protocol combining feed restriction followed by 1-h concentrated meals and to assess the resulting hepatic metabolic responses. To achieve this, two protocols were tested. The first protocol initially demonstrated that a 5-day acclimation phase, consisting of alternating 23-h fasting periods and 1-h refeeding periods, was necessary to induce hyperphagia in ducks. Then, an increase in liver weight and glycogen content was measured up to 12 h after the substantial meal, before returning to baseline after 24 h, whereas total lipid levels remained unchanged. Based on these observations, a second protocol was designed to assess whether an additional meal provided 12 h after the last substantial meal could promote lipid storage in the liver. A significant increase in liver weight and glycogen content was measured after each 1-h meal, whereas total hepatic lipid content increased significantly after the last meal provided 12 h after the previous one. This was associated with an upregulation of genes involved in lipogenesis (<i>FASN</i>, <i>SCD1</i>, and <i>ELOVL6</i>) and carbohydrate oxidation (<i>HK1</i>), and a downregulation of a gene involved in lipid oxidation (<i>ACSL1</i>). Together, these results demonstrate for the first time that voluntary feeding alone can induce measurable hepatic lipid accumulation in mule ducks. This new protocol represents a valuable experimental model for the study of hepatic lipid metabolism in ducks and could contribute to the development of alternative strategies for liver fattening.<b>NEW & NOTEWORTHY</b> This study provides new insights into the physiological effects of a substantial voluntary meal on hepatic energy metabolism in the mule duck, a species for which information on this topic remains limited. Our findings show for the first time that hepatic lipid deposition can be induced through voluntary feeding, without the need for force-feeding. In the longer term, these results may support the development of alternative practices to force-feeding for foie gras production.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R451-R462"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147519708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive modeling of putamen dopamine in Parkinson's disease: relevance to prognosis, treatment, and prevention.","authors":"David S Goldstein","doi":"10.1152/ajpregu.00027.2026","DOIUrl":"10.1152/ajpregu.00027.2026","url":null,"abstract":"<p><p>Depletion of putamen dopamine (DA) characterizes Parkinson's disease (PD) and precedes the onset of motor symptoms by years. Increasing evidence implicates impaired vesicular sequestration and attenuated detoxification of the toxic catecholaldehyde 3,4-dihydroxyphenylacetaldehyde (DOPAL) in disease pathogenesis. We applied a mechanistic kinetic model to examine how perturbations in dopamine handling from DOPAL-induced autotoxicity affect the timing and trajectory of symptomatic PD. Using an icon-based application we constructed a model of intraneuronal dopamine synthesis, vesicular storage, leakage, metabolism, aldehyde detoxification, delayed toxicity, and α-synuclein modification. Model behavior was evaluated by internal consistency and concordance with empirical cellular, animal, imaging, and postmortem neurochemical data. We examined predicted effects of genetic variants, acquired factors (e.g., stress, environmental exposures), and treatments on vesicular dopamine content across the lifespan. Without imposing a predefined disease curve, the model generated a triphasic trajectory of vesicular dopamine loss-homeostasis, dyshomeostasis, and symptomatic decline-from delayed DOPAL-mediated toxicity, with progressive impairment of vesicular sequestration and other intraneuronal processes. The model predicted that genetic decreases in vesicular uptake or aldehyde detoxification and increases in dopamine biosynthesis would shorten the time to the onset of symptomatic disease, whereas monoamine oxidase inhibition, levodopa, and antioxidant treatment applied early and in combination would be protective. Preclinical, multitarget interventions would delay or prevent crossing a symptomatic threshold within the modeled lifespan. Systems modeling across the lifespan predicts a triphasic decline in putamen dopamine stores in PD. The timing and combination of interventions may be decisive for delaying or preventing symptomatic disease.<b>NEW & NOTEWORTHY</b> We used kinetic modeling to predict the temporal course of putamen dopamine depletion across the lifespan in Parkinson's disease and predict effects of autotoxicity, genetics, environmental exposures, and possible treatments on the timing of the onset of symptomatic disease.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":"R512-R529"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147571939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Publisher's note for Sá et al., volume 328, 2025, p. R481-R491.","authors":"","doi":"10.1152/ajpregu.00092.2026_NOT","DOIUrl":"https://doi.org/10.1152/ajpregu.00092.2026_NOT","url":null,"abstract":"","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":"330 5","pages":"R563"},"PeriodicalIF":2.3,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832444","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low-dose Simulated Galactic Cosmic Radiation Exposure After Hindlimb Unloading Has Long-term Impact on Skeletal Muscle Metabolic Proteins in Female Mice.","authors":"Matthew Martone, Brian A Irving, Guillaume Spielmann, Neil M Johannsen, Matthew M Robinson, Jeffery C Chancellor, Heather C M Allaway","doi":"10.1152/ajpregu.00014.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00014.2026","url":null,"abstract":"<p><p><b>Background:</b> Spaceflight stressors, including microgravity-induced unloading and galactic cosmic radiation (GCR), acutely disrupt mitochondrial function and contribute to skeletal muscle atrophy. The long-term remodeling of skeletal muscle following combined unloading and radiation exposure remains poorly understood. We investigated protein abundance changes 9-months post-exposure to combined unloading and radiation exposure. <b>Methods:</b> Female, 6-month old, C57Bl/6J mice underwent 5 days of hindlimb unloading (HU) or weight-bearing (WB) conditions, followed by 0Gy, 0.5Gy, or 1.5Gy of simulated GCR exposure using the simplified 5-ion beam exposure (simGCRsim) (n=5/group). The gastrocnemius muscle was collected after 9-months of WB and analyzed by data-independent acquisition mass spectrometry. Differentially abundant proteins were identified and evaluated using pathway enrichment analyses. <b>Results:</b> WB mice exposed to 0.5Gy exhibited increased abundance of electron transport system proteins and mitochondrial transport proteins, suggesting increased mitochondrial activity relative to control mice. HU mice exposed to 0.5Gy displayed decreased glycolytic proteins, increased reliance on oxidative pathways, and reduced antioxidant proteins (glutaredoxins, peroxiredoxin) compared to WB0.5. In HU mice, a higher radiation dose (HU1.5 vs HU0.5) led to the downregulation of 26S proteasome subunits and the upregulation of peroxisomal antioxidant, tricarboxylic acid cycle, and β-oxidation proteins, indicating dose-dependent mitochondrial adaptations. <b>Conclusion:</b> Long-term muscular remodeling after simGCRsim exposure is influenced by both muscle loading status and radiation dose, with prolonged shifts toward oxidative metabolism and altered protein quality control persisting months after exposure. These findings provide new insights into skeletal muscle adaptation to spaceflight stressors and have important implications for astronaut health during and after long-duration missions.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Sex and Menstrual Cycle Phase on Post-Exercise Appetite Regulation.","authors":"Jessica A L Tucker, Seth F McCarthy, Derek P D Bornath, Jordyn M Frayne, David A Claeys, Joshua Aube, Tamara R Cohen, Philip J Medeiros, Tom J Hazell","doi":"10.1152/ajpregu.00328.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00328.2025","url":null,"abstract":"<p><strong>Introduction: </strong>Moderate-intensity exercise interventions for weight loss are less effective in females, suggesting biological sex and fluctuations in menstrual cycle hormones may be involved. To date, no study has explored the post-exercise appetite response between males, females in the follicular phase (FP) and females in the luteal phase (LP).</p><p><strong>Purpose: </strong>To examine differences in appetite regulation in response to an acute bout of moderate-intensity continuous training (MICT) between males, females in the FP, and females in the LP.</p><p><strong>Methods: </strong>Males, FP, and LP females (n=14 per group; n=42 total) completed a single bout of MICT (30 min, 70% V̇O₂max). Acylated ghrelin, active glucagon-like peptide-1 (GLP-1), and subjective appetite perceptions were measured pre-exercise and 0-, 30-, 60- and 120-min post-exercise. Energy intake was assessed for a 3-day period (day before, of, after).</p><p><strong>Results: </strong>There were no between-group differences in acylated ghrelin (P=0.388, η²ₚ=0.047) or active GLP-1 (P=0.413, η²ₚ=0.044). Subjective appetite was lower pre-exercise in males compared to both females in the FP (P=0.087, d=0.85) and LP (P=0.013, d=0.65) with no other between-group differences. Absolute energy intake was greater in males compared to females in the LP only (P=0.032, η²ₚ=0.111), however when analyzed relative to body mass there were no between-group differences (P=0.306, η²ₚ=0.062).</p><p><strong>Conclusion: </strong>There were no differences in the response to MICT for appetite-regulating hormones, subjective appetite, or energy intake between males or females in either phase. Further work should consider exploring appetite following high-intensity exercise to thoroughly investigate if sex differences on hormonal and subjective appetite regulation are present.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expiratory loading modulates the quadriceps muscle pump-induced venous return during rhythmic isometric exercise.","authors":"Kana Shiozawa, Haruna Kondo, Natsuki Seo, Koji Ishida, Shigehiko Ogoh, Keisho Katayama","doi":"10.1152/ajpregu.00052.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00052.2026","url":null,"abstract":"<p><p>During exercise, venous return is enhanced by the skeletal muscle pump. Expiratory loading increases intra-abdominal pressure, which may impede venous return from the lower limbs. However, its effect on venous return mediated by the quadriceps muscle pump remains unclear. The purpose of this study was to elucidate the effect of expiratory loading on venous return facilitated by the quadriceps muscle pump. Healthy young participants performed rhythmic unilateral isometric knee-extension exercise of the right quadriceps (10% maximal isometric voluntary contraction; 2 s contraction/2 s relaxation), and data was successfully obtained from twelve participants. Controlled breathing (breathing frequency: 15 breaths/min; inspiratory-to-expiratory ratio: 1:1; tidal volume: twice the resting tidal volume) was performed with and without expiratory load. The expiratory phase was synchronized with the contraction phases. Expiratory load was adjusted to produce a mouth pressure of 20 cmH2O during expiration. Quantity of blood flow in the right femoral vein (Qfv) was continuously measured using Doppler ultrasound. No significant differences were observed in the increases in force and electromyography during expiration between the non-loading and loading conditions. Quadriceps muscle contraction increased Qfv; however, the contraction-induced increase was smaller (P = 0.005) with expiratory loading (497.6 ± 350.5 mL/min, mean ± standard deviation) than without expiratory loading (694.8 ± 358.9 mL/min). These findings suggest that increased expiratory loading may partly reduce the effectiveness of the quadriceps muscle pump in facilitating venous return during light-intensity exercise.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B-Raf is required for normal murine cardiac development and function.","authors":"Natasha N Chattergoon, Katherina P Rees, Sara Lescher, Maho Takahashi, Philip J S Stork","doi":"10.1152/ajpregu.00063.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00063.2025","url":null,"abstract":"<p><p>Developing cardiomyocytes grow by proliferative and hypertrophic pathways and can be mediated by the RAF/MEK/ERK (MAPK) pathway. Dysregulation of Raf-1 in late development causes murine myocardial hypertrophy, however, less is known about B-Raf. We hypothesized the loss of B-Raf (conditional knockout) would lead to reduced neonatal cardiomyocyte proliferation and accelerate maturation, resulting in impaired function in adulthood. We also determined sex differences to ensure complete interrogation of the model. Murine neonatal hearts undergo a proliferative to terminal differentiation switch that is complete by 2 weeks of age and thus studied hearts at four timepoints in that period (Days 1, 3, 8, 14). Primary cultures of knockout (KO) hearts revealed reduced B-Raf and phosphorylated ERK1/2 by postnatal day 3, even when stimulated with insulin growth factor 1. Histology revealed increased cardiomyocyte volume in KO hearts by 3d and elevated markers of hypertrophy and maturation by 8d (mTOR and SERC2A). There was also elevated cell cycle inhibitors p21, p27 and p53, accompanied with increased cyclin levels. Heart weight to body weight ratio was greater in 8d KO compared to age matched wildtype (WT) animals as well as other KO ages, whereas there was no difference among WT ages. Earliest signs of altered myocardium via echocardiographs were detected by 3 months. KO mice exhibited dilated cardiomyopathy, thinned myocardial walls, and enlarged left chamber volume. Deletion of B-Raf led to adaptive remodeling of male KO hearts. This adaptation maintains cardiac function however future studies will interrogate changes in the face of physiological stress.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-Altitude Exercise Performance and Acute Mountain Sickness Unchanged Following Cold Water Habituation.","authors":"Afton D Seeley, Thomas A Mayer, Billie K Alba, Phillip O Bodurtha, Karleigh E Bradbury, Shaun C Brazelton, Aaron R Caldwell, K Riley Connor, Gabrielle E W Giersch, Samantha J Goldenstein, David H Gonzalez Rojas, Benjamin A Fry, Andrew M Greenfield, Molly E Heikkinen, Kathryn G McCarthy, Benjamin J Ryan, Roy M Salgado, MariaLena A Shaw, John W Castellani","doi":"10.1152/ajpregu.00149.2025","DOIUrl":"https://doi.org/10.1152/ajpregu.00149.2025","url":null,"abstract":"<p><p>Cross stress adaptation (CA) refers to the induction of physiological adaptation to one stimulus, such as cold water, to adaptively influence the physiological response to another novel stimulus, such as hypoxia. This study sought to determine if cold-hypoxia CA, induced by repeat cold water immersion (CWI) and compared to a thermoneutral water (TN) control, could reduce resting and submaximal exercise physiologic strain, improve exercise performance, and decrease the incidence and severity of acute mountain sickness (AMS) symptoms during a 29-h exposure to hypobaric hypoxia (~4100m). Cold ventilatory habituation was achieved, evidenced by an ~20% reduction in peak minute ventilation (V_E) and ~31% reduction in 10-min average V_E with six, 10-min 12°C water immersions. At 3h of hypobaric hypoxia, an exercise bout at 50% VO_2peak elicited greater ventilation (+3.8 [0.8-6.7] L·min^-1, <i>p</i> = 0.014) with no concomitant improvement of SpO₂ (TN: 76 ± 4 vs. CWI: 76 ± 4%, <i>p</i>> 0.05) following CWI. Exercise heart rate was also elevated following CWI compared to TN, irrespective of altitude exposure duration (+5 [1-8] beats·min^-1, <i>p</i>= 0.030). Two-mile time trial performance and AMS symptomology were both unchanged by repeated CWI compared to TN. Habituation to repeated cold-water immersion does not advantageously cross adapt those subsequently exposed to hypobaric hypoxia. Instead, CWI heightened early altitude ventilatory and cardiovascular strain during submaximal exercise.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging Diminishes Thymic Output, Reduces Naive T Cells, Promotes Memory T-Cell Accumulation, and Impairs Thymic Regeneration.","authors":"Daria M Konovalova, Madison D Cooper, Shuli Huang, Danielle X Shane, Jordyn S Mulhern, Ying Ann Chiao, Sarah Y Yuan, Yonggang Ma","doi":"10.1152/ajpregu.00242.2025","DOIUrl":"10.1152/ajpregu.00242.2025","url":null,"abstract":"<p><p>Aging increases susceptibility to a wide range of diseases, partially due to alterations in T lymphocytes. This study aimed to characterize age-related changes in T-cell output, phenotype, and function under basal conditions and after myocardial infarction (MI). Compared with young mice (2-6 months), aged mice (≥18 months) demonstrated reduced thymic size and fewer developing thymocytes. Accordingly, circulating T-cell counts were significantly lower in aged mice than in young mice. Interestingly, the spleen and bone marrow of aged mice showed increased T-cell accumulation, primarily due to expansion of memory T cells. Similarly, older humans (≥60 years old) exhibited reduced circulating T cells and a higher proportion of memory T cells. Under basal conditions, aged splenic T cells expressed higher mRNA levels of pro-inflammatory and cytotoxic factors (e.g. <i>Ifnγ</i>, <i>Tnfα</i>, <i>granzyme b</i>, and <i>perforin</i>). Moreover, aged T cells exhibited a higher frequency of PD-1⁺, TIGIT⁺, LAG-3⁺, and CTLA-4⁺ cells compared to young T cells, indicative of an exhausted phenotype. Metabolically, aged T cells showed higher basal glycolytic and mitochondrial oxidative phosphorylation. Following MI, thymic regeneration was evident in young mice by day 14, whereas the aged thymus remained atrophic. Additionally, aged MI mice exhibited reduced naïve T cells and increased memory T cells in the spleen and bone marrow than young mice. In conclusion, our study reveals that aging diminishes thymocyte output and circulating T-cell pools, facilitates memory T-cell accumulation, and compromises thymic regeneration under basal conditions and post-MI.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac autonomic regulation across the menstrual cycle is highly individual: Evidence from phase-aligned cyclic generalized additive mixed models.","authors":"Marcelle Schaffarczyk, Lucie Rückemann, Billy Sperlich, Thomas Gronwald","doi":"10.1152/ajpregu.00028.2026","DOIUrl":"https://doi.org/10.1152/ajpregu.00028.2026","url":null,"abstract":"<p><p>Cardiac autonomic regulation, indexed by heart rate variability (HRV), is hypothesized to fluctuate across the menstrual cycle. Empirical findings remain inconsistent, likely due to sparse phase-based sampling and limited consideration of interindividual variability. This study examined cyclic HRV trajectories using longitudinal monitoring and phase-aligned cycle time scaling (PACTS) to distinguish population-level from individual-specific patterns and to evaluate associations with well-being. Daily HRV (smartphone photoplethysmography) and well-being were collected in 21 naturally cycling women. Cycle time was aligned using PACTS, with ovulation set to 0 and follicular and luteal phases rescaled to a common -1 to +1 interval. Vagally mediated HRV was indexed using log-transformed RMSSD (ln(RMSSD)) and the coefficient of variation (CV) of ln(RMSSD), calculated from a centered rolling window. Cyclic generalized additive mixed models separated population-level smooths from participant-specific cyclic deviations. Associations between well-being (sleep quality, stress, fatigue, muscle soreness) and HRV were examined using mixed-effects models distinguishing within- and between-person effects. For ln(RMSSD), the population-level cyclic trajectory was flat and non-significant, whereas participant-specific cyclic deviations were significant, indicating pronounced interindividual heterogeneity despite a stable average pattern. Similar results were observed for CV ln(RMSSD). Within-person analyses showed that poorer sleep quality, higher stress, and greater fatigue were associated with lower ln(RMSSD), while between-person differences were unrelated to mean HRV. Increases in stress and muscle soreness were associated with modest increases in HRV fluctuations. When menstrual cycle timing is precisely aligned to ovulation, vagally mediated HRV shows no consistent population-level rhythm but marked individual-specific dynamics, strongly modulated by day-to-day well-being.</p>","PeriodicalId":7630,"journal":{"name":"American journal of physiology. Regulatory, integrative and comparative physiology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}