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Brain derived neurotrophic factor (BDNF) signals through its high-affinity full-length tropomyosin receptor kinase-B (TrkB.FL) and plays role in maintaining the survival and function of phrenic motor neurons (PhMNs), neuromuscular transmission and synaptic activity. Disruption of this pathway is a hallmark of several neurodegenerative diseases associated with dysfunction and death of PhMNs with impaired mitochondrial function. BDNF/TrkB.FL signaling phosphorylates CREB at serine 133 (pCREBS133) and promotes its nuclear localization in cervical ventral horn of rats, however its downstream molecular pathway has not yet been established. Recently, we demonstrated that in human airway smooth muscle cells, pCREBS133, as a transcription factor, binds to the CRE sequence in the PGC1a promoter and activates its expression. PGC1a co-transcriptionally activates mitochondrial transcription factor A (TFAM) expression promoting mitochondrial DNA (mtDNA) replication and mitochondrial biogenesis. In the present study, we hypothesized that BDNF/TrkB.FL signaling promotes pCREBS133 phosphorylation and transcriptional activation of PGC1a and downstream expression of TFAM, leading to mitochondrial biogenesis. In this study, we employed a loss of function approach using a novel chemogenetic rat model (TrkBF616A) with a knock-in allele sensitive to the selective kinase inhibitor 1NMPP1 to inhibit TrkB.FL kinase activity. One group of female and male rats were treated intrathecally at C4 with either artificial cerebrospinal fluid (aCSF) or BDNF (450 ng/ 300 g b.w.; diluted in aCSF) for 40 mins, followed by collection of C3-C6 cervical ventral horn. In a second group, female and male rats were treated with 1NMPP1 (25 uM; i.p.) or the vehicle DMSO for 2 h. After 2 h, both groups were treated intrathecally with BDNF for 40 min and the C3-C6 cervical ventral horn collected. Intrathecal BDNF increased the pTrkB.FLY817 autophosphorylation and downstream phosphorylation of pCREBS133. Bioinformatic analysis identified a putative binding site of pCREBS133 on PGC1a promoter, which was confirmed by Chromatin immunoprecipitation (ChIP) assay. Consistent with this, BDNF treatment increased the expression of PGC1a and downstream TFAM, with an increase in mtDNA copy number. 1NMPP1 inhibition of TrkB.FL kinase (blunted BDNF-induced pTrkB.FLY817 phosphorylation) inhibited downstream activation of the pCREBS133/PGC1a/TFAM signaling cascade. Additionally, 1NMPP1 treatment blunted the BDNF-induced increase in mtDNA copy number. We conclude that BDNF/TrKB.FL signaling mediates mitochondrial biogenesis in the cervical ventral horn suggesting that interventions targeting this pathway could be a therapeutic strategy for neurodegenerative diseases. This research was funded by NIH Grants HL146114 & AG44615. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Alzheimer’s disease (AD) is characterized by profound metabolic dysfunction and disturbances in gut–brain axis signaling. Ketogenic diet (KD) has demonstrated metabolic and cognitive benefits in both preclinical and clinical studies. However, factors that determine individual responsiveness or non-responsiveness to KD interventions remain poorly understood. Emerging evidence suggests that gut microbiome composition plays a critical role in modulating these factors. This study examined how KD responsiveness, determined by fecal microbiota transplantation (FMT) derived from human KD responders (RES) or non-responders (nRES)- influences cognition, gut barrier function, neuroinflammation, and microbial structure in 3xTg-AD mice. We further evaluated whether supplementing KD with a novel Synbiotic Yogurt (SY) formulated by our team could augment or restore responsiveness. We hypothesized that RES microbiota would confer superior KD-driven benefits and that KD-SY would synergistically improve metabolic and neurobiological outcomes, particularly among nRES recipients. Adult 3xTg-AD mice were antibiotic-cleansed and randomized to receive Control-, RES-, or nRES – FMT, while maintained on KD for four weeks. A second cohort received KD supplemented with SY or non-fat milk along with RES- or nRES-FMT. Behavioral tests, gut permeability assay, serum inflammatory markers, brain amyloid beta (Aβ), intestinal morphology, gene expression, and 16S rRNA microbial profiling were measured. RES-FMT recipients showed early improvements in spatial memory (Y-maze and novel object recognition) and consistently lower Aβ accumulation in cortex and hippocampus. They also showed higher synaptophysin and IL-10 expression. In contrast, nRES-FMT mice exhibited distinct microbiome clustering, lower microbial diversity, enrichment of Proteobacteria, and impaired gut barrier function relative to RES-FMT recipients. Functionally, specific taxa like Enterococcus, Enterobacter, and Paenibacillus were associated with greater vulnerability to AD-related pathology, while Akkermansia, Bifidobacterium, and Muribaculum were linked with lower vulnerability. SY supplementation improved metabolic and gut barrier indices across groups characterized by increased circulating ketone levels, lowered fasting glucose and glucose-ketone index, and decreased gut permeability. nRES-SY mice showed the strongest gains in recognition memory and reductions in brain Aβ1–42 burden. SY increased expression of barrier- and inflammation-modulating genes, including occludin, APLP2, and IL-10. Microbiome analysis demonstrated higher microbial diversity and enrichment of beneficial genera such as Paralactobacillus, Eubacterium, and Muribaculum. These findings show that KD responsiveness is strongly determined by gut microbiota composition and that SY supplementation can enhance or rescue metabolic, cognitive, and microbial outcomes, particularly in nonresponders. This supports a precision-microbiome strategy combining metabolic and Synbiotic interventions to improve gut–brain axis function in AD. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

In the aerodigestive system (ventilation, swallow, speech and airway defense manoeuvres), age-related neuromotor declines contribute to the increased risk of aspiration pneumonia, a leading cause of mortality in the elderly. In the Fischer 344 (F344) rat model, we and others have identified that brainstem hypoglossal motor neuron (MN) degenerations and death contribute to motor dyscoordination and tongue muscle weakness, respectively. In F344 rats, both MNs and striated muscle exhibit morphological and functional deficits of mitochondria in aging, consistent with elderly human post mortem results. However, to date the dendritic and axonal compartments have been relatively ignored. In young (6-months old; n=6 rats) and old (24-months-old; n=6 rats) female and male F344 hypoglossal motor axons were assessed using serial block face scanning electron microscopy (SDFEM). Within myelinated hypoglossal motor axons and hypoglossal MN dendrites, mitochondrial volume density and morphology (mitochondrial CSA, form factor and aspect ratios) were assessed. In old age, mitochondrial volume density was reduced in dendrites and, surprisingly, increased in axons. Mitochondrial fragmentation (reduced CSA, form factors and aspect ratios was apparent in dendrites. In axons, old age mitochondria were larger, but more simplistic. We interpret these dendritic findings to be consistent with altered neural network function in old age. In the axons, excessive mitochondria may physically impair the anterograde and retrograde transit along the axons. Our results suggest that a more nuanced compartment-specific evaluation of mitochondrial structure and function is required to fully elucidate the pathophysiology underlying age-related neuromotor dysfunction. Funding for this research was provided by National Institutes of Health (NIH) grant AG086136 (MJF). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Tongue-muscle associated behaviours (swallow, speech) are impaired in the elderly. In the Fischer 344 (F344) rat model of aging, hypoglossal MNs and intrinsic tongue muscle weakness and atrophy are evident. Here we evaluated young (6-months; n=6 rats) and old (24-months-old; n=6 rats) F344 rat longitudinal muscles for neuromuscular junction (NMJ) innervation. In 140 µm free floating sections, presynaptic components were labelled with synaptophysin and neurofilament. Postsynaptic acetylcholine receptors were labelled with α-Bungarotoxin. NMJs were imaged using confocal microscopy with presynaptic invasion of the postsynaptic endplate quantified (n=200 young NMJs, n=180 old NMJs). We found marked denervation of tongue NMJs in old age,. Our findings underpin the significant role that tongue dysfunction has in the increased risk of aspiration pneumonia and obstructive sleep apnea in the elderly. This study was supported by R56 HL166204 (MJF), R01 AG086136 (MJF) and AG44615 (GCS) from the NIH. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Preeclampsia (PE) is a hypertensive disorder of pregnancy defined by new-onset hypertension occurring after 20 weeks of pregnancy, with end organ damage. Pro-inflammatory changes are also observed in these patients. Although the clinical features of PE are resolved soon after delivery, affected patients face a higher risk and earlier onset of cardiovascular disease (CVD). It is unknown what leads to this persistent elevated risk, and long-term alterations of the maternal immune system could be involved. Study objective: Our goal was to address the immune alterations and functional changes in the first year postpartum in PE as compared to normotensive (NT) pregnancies. Hypothesis: We hypothesize that the maternal immune profile is altered in the postpartum period in PE vs NT patients, with a proinflammatory bias and altered function in PE patients. Brief Statement of Methods: We prospectively followed 31 women (PE=15, NT=16) and collected blood 24 hours, and 3, 6, and 12 months postpartum. Plasma and peripheral blood mononuclear cells (PBMC) were isolated and stored for analysis. Inflammatory mediators were quantified through multiplex assays, and PBMCs profile were defined through flow cytometry as well as following inflammatory stimuli to assess their functional changes through intracellular cytokine staining and expression of activation markers. Summary of Results: PE patients had elevated CD3+ T cell frequencies at 3 and 12 months postpartum compared to NT patients. Both groups showed reduced CD14+ monocytes across postpartum timepoints compared with 24 hours. PE was also associated with increased amounts of pro-inflammatory cytokines (such as IL1α, IL9, IFNγ), chemokines and growth factors at multiple timepoints throughout the first year postpartum; NT patients had decreased amounts of pro-inflammatory cytokines. Intracellular staining showed altered immune cell functions in PE, with decreased IL-6 production following polyI:C stimulation and decreased IL-10+ monocytes after LPS and polyI:C at 3 months postpartum. At 3 months, PE patients had increased markers of activation (i.e. CD69+) in both NK cells and T cells, the latter following PMA/Ionomycin stimulation. Statement of Conclusions: Pregnancy itself induces lasting immune changes persisting to 12 months postpartum, even in NT patients, whilst PE complicated pregnancies have sustained inflammation and altered immune function in the postpartum period. Overall, this work will provide essential insight into an understudied period that many women experience and help to identify long lasting immunological changes that could impact long term maternal health. Future work will explore the impact of this sustained inflammation on epigenetic modifications in immune cells. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Background: Cardiovascular-Kidney-Metabolic (CKM) syndrome entails pathophysiological interactions leading to multiorgan dysfunction and a high rate of cardiovascular morbidity and mortality, largely driven by the development of heart failure (HF). Mechanisms leading to HF in CKM syndrome are unknown. We created a model of CKM syndrome in swine and showed that cardiac abnormalities associate with cardiac microvascular (MV) rarefaction and decreased expression and availability of VEGF. Emerging research focuses on micro-RNAs (miRNAs) and their role in the pathophysiology of HF, but whether they play a role in the development of cardiac injury in CKM syndrome via VEGF modulation has not been investigated. We aimed to identify specific miRNAs that can target VEGF to test the hypothesis that their direct cardiac inhibition will rescue cardiac VEGF, improve angiogenic signaling, and cardiac hemodynamics in CKM syndrome. Methods: CKM (bilateral renal artery stenosis+high-cholesterol/high-carbohydrate feeding) and normal pigs (n=4 each, 2 males/2 females) were studied for 14 weeks. Unbiased micro-RNA sequencing identified 26 miRNAs differentially expressed in CKM pig hearts, of which only miR-452-5p can target VEGFA, which was confirmed by pulldown analysis and qPCR. In addition, CKM (n=4, 2 males/2 females) were treated after 6 weeks with a single intracoronary (IC) administration of a miR-452-5p inhibitor (antagomiR). Cardiac hemodynamics (echocardiography), MV architecture (3D micro-CT) and cardiac expression of VEGF and miR-452-5p (RT-qPCR) were quantified before IC miR-452-5p inhibition, and again at the end of the study (14 weeks). Results: Pigs with CKM syndrome showed blunted diastolic relaxation, increased cardiac remodeling, and reduced subendocardial MV density and cardiac VEGF expression, accompanied by higher cardiac expression of miR-452-5p compared to normal pigs. Notably, most of these parameters were improved after in vivo IC miR-452-5p inhibition (single dose). Blood pressure was unchanged ( Table 1 ). Conclusions: Our study supports a role for VEGF in preserving cardiac MV integrity in CKM syndrome. Also, it identifies a targeted post-transcriptional regulation of VEGF via miR-452-5p and supports the feasibility and efficacy of its mechanistic modulation in vivo. The predictive power of our model conceptually supports the potential of a novel targeted intervention to protect the heart in CKM syndrome. [Table: see text] Support: NIH AG084154 (ARC), and DK129240 (AE) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Rationale: Respiratory disease is a major cause of mortality in Down syndrome (DS; trisomy 21, T21). DS is considered a progeroid syndrome, with elevated cellular senescence (SEN) and oxidative stress. Because SEN shapes organogenesis, its dysregulation may impair lung morphogenesis. We previously found SEN/SASP (senescence-associated secretory phenotype) abnormalities in prenatal human T21 lungs. Here, we test whether these alterations persist and change after birth. Methods: We analyzed human lung single-nuclear RNA (snRNA-seq) datasets (prenatal and postnatal) to quantify epithelial and mesenchymal SEN/SASP signatures. Sex- and age-matched T21 and non-T21 prenatal and postnatal lungs were studied; fibroblasts were isolated as prenatal human lung fibroblasts (HFLF) and postnatal human lung fibroblasts (HLF). SEN/SASP were measured by RT-qPCR and immunofluorescence (IF) in tissue and HFLF/HLF. HFLF/HLF were assayed for SA-β-gal, oxidative stress (CellROX/MitoSOX), and Ca 2 + dynamics (Fura-2 AM). 48h treatments with tunicamycin (1µM, SEN inducer), 4-phenylbutyrate (4-PBA, 2 mM, ER Stress inhibitor), or pyrroloquinoline quinone (PQQ, 20 μM, antioxidant) were performed on T21 and non-T21 HFLF/HLF. Conditioned media (CM) were collected after 48h from untreated cultures and then applied to cells of the opposite genotype for 24, 48, and 72h. Results: Overall SEN profile was similar in epithelium and mesenchyme across ages, but pathway signatures differed. Epithelium shows an inflammatory SASP, while mesenchyme shows a less-inflammatory, remodeling/growth-factor SASP. These lineage patterns were more evident postnatally. Whole-tissue IF showed increased γ-H2AX and p21 in T21 vs non-T21 both prenatally and postnatally (p< 0.05). At baseline, T21 HFLF/HLF had higher CDKN1A, CDKN2A, TP53, CDKN2B, and SERPINE1 (p< 0.05; n=5–6), with increased γ-H2AX/p21 IF (p< 0.01; n=6), SA-β-gal (p< 0.05; n=5–6), and ER/mitochondrial stress (p< 0.05; n=5–6). Fura-2 AM showed greater Ca 2 + release in T21 HFLF/HLF at baseline and after acetylcholine (10 μM, p< 0.01; n=5). Mitochondrial-morphology genes (FIS1, DNM1L, MFN1) were elevated in T21 HFLF/HLF (p< 0.05; n=6). In T21 HFLF, 4-PBA and PQQ each reduced SA-β-gal (p< 0.01; n=6). In postnatal HLF, PQQ had the stronger effect (p< 0.05; n=5). T21 CM induced progressively greater SEN/SASP over 24/48/72h in non-T21 cells (p< 0.05; n=5-6), while non-T21 CM partially rescued T21-HLF phenotypes at 24h only (p< 0.05; n=5-6). Conclusion: These data indicate that lung senescence in T21 initiates in utero and intensifies after birth and reflects lineage-specific pathways. ER-stress-related mechanisms are more prominent prenatally, while mitochondrial/redox mechanisms are predominant postnatally. This evidence suggests age and lineage-dependent drivers of senescence that may help explain DS lung disease and highlight potential new mechanistic targets. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Our knowledge regarding baroreflex regulation of subpopulations of differently sized sympathetic action potentials (APs) remains incomplete. This study tested the hypothesis that baroreflex sigmoid morphology varies across AP subpopulations. In 12 healthy individuals (6 females; 32 ± 5 years), we measured diastolic blood pressure (DBP; brachial artery catheter) and muscle sympathetic APs (peroneal microneurography; continuous wavelet transform) during a modified Oxford protocol (100 μg nitroprusside bolus, 150 μg phenylephrine bolus). Baroreflex sigmoids (four-parameter logistic functions) modelled the relationship between DBP and sympathetic AP discharge probability for 10 normalized AP clusters. For each AP cluster, baroreflex sigmoid morphology was quantified by max gain, threshold, centering, and saturation pressures, and operating and response ranges. One-way analyses of variance and Dunnett post-hoc tests were performed. Data are mean ± SD. At the centering pressure of the baroreflex sigmoid, max gain was greater for medium APs (e.g., Cluster 3: -5.6 ± 2.9%/mmHg) compared to small (e.g., Cluster 1: -1.4 ± 1.1%/mmHg; P < 0.01) and large APs (e.g., Cluster 9: -0.6 ± 0.4%/mmHg; P < 0.01). Discharge probability at the centering pressure was also greater for medium APs (e.g., Cluster 3: 61 ± 22%) compared to small (e.g., Cluster 1: 12 ± 10%; P < 0.01) and large APs (e.g., Cluster 9: 3 ± 3%; P < 0.01). There were no differences in the saturation pressure (i.e., DBP where any further reduction does not elicit an increase in AP discharge probability) between AP clusters (main effect P = 0.22). The threshold pressure (i.e., DBP where any further reductions elicit an increase in AP discharge probability) was greater for medium (e.g., Cluster 3: 78 ± 8mmHg) compared to large APs (e.g., Cluster 9: 74 ± 11mmHg; P = 0.03). The operating range (i.e., Threshold – Saturation DBP) was greater for medium (e.g., Cluster 3: 14 ± 3mmHg) compared to large APs (e.g., Cluster 9: 8 ± 5mmHg; P < 0.01). There were no differences in the threshold pressure or operating range of medium compared to small APs (both P ≥ 0.82). The response range (i.e., Saturation – Threshold discharge probability) was greater for medium (e.g., Cluster 3: 26 ± 13%) compared to small (e.g., Cluster 1: 5 ± 4%; P < 0.01) and large APs (e.g., Cluster 9: 1 ± 1%; P < 0.01). These data confirm prior work using linear modeling and spontaneous approaches to quantify sympathetic AP baroreflex gain and extend to demonstrate variation in the morphology of the baroreflex sigmoid. During large changes in blood pressures, we identify differences in broader features of baroreflex control (e.g., threshold pressure, operating range, and response range) between AP subpopulations that support strong baroreflex regulation over medium-sized APs. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

The motor unit consists of an individual motor neuron (MN) and the muscle fibers it innervates. In humans and rodents, muscle weakness in aging (sarcopenia) has focused on altered motor unit discharge properties and intrinsic skeletal muscle pathophysiology, with MNs relatively ignored. In the brainstem, the intrinsic and extrinsic tongue muscles are innervated by hypoglossal MNs. In the spinal cord, the hindlimb muscles are innervated by the lumbar motor enlargement. Both aerodigestive and locomotor behaviours are affected in old age. In Fischer 344 rats, age-related MN death is evident by 24 months, disproportionately affecting larger (likely fast fatiguable motor unit) MNs. Here, we evaluated hypoglossal and lumbar MN survival in female and male Sprague Dawley rats at young (6-months-old; n=12) and old (24-months-old; n=6) ages. Stereological assessment of hypoglossal MN numbers and surface areas were performed on 16 µm Nissl-stained brainstem and spinal cord cryosections. We observed a robust loss of ~20% of hypoglossal MNs and a modest ~15% reduction in their surface areas with age. In the larger size tertile of hypoglossal MNs, age-associated loss of MNs approached ~30%. Similarly, we observed an ~20% lumbar MN loss, with a striking ~25% reduction in somal surface area. In the larger size tertile of lumbar MNs, age-associated loss of MNs approached ~40%. These findings underscore a marked neurogenic component to age-related neuromotor dysfunction, with reliability of findings across rat strains. This MN death likely contribute to physiologically relevant aerodigestive and locomotor impairments in old age. This study was supported by R56 HL166204 (MJF), R01 AG086136 (MJF) and AG44615 (GCS) from the NIH. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Mitochondrial quality control is maintained by coordinated turnover mechanisms involving mitophagy (removal of damaged mitochondria) and mitochondrial biogenesis (generation of new mitochondria). Disruption of either one or both processes results in the accumulation of damaged mitochondria, oxidative stress and subsequently impaired cellular function. In human airway smooth muscle (hASM) cells, such impairment compromises sustained ATP production required for contractile responses. A key regulator of this balance is PARIS (ZNF746), a transcriptional repressor of PGC1α. Accumulated PARIS binds upstream to the promoter of PGC1α and interferes with the recruitment of transcriptional activators, resulting in decreased PGC1α transcription and reduced mitochondrial biogenesis. In addition, PARIS is implicated in the disruption of cellular antioxidant defense mechanisms due to its direct interaction with NRF2 transcriptional complex. Under basal conditions, PARIS levels are tightly regulated by post-translational modifications such as ubiquitination and phosphorylation. As a target of PINK1/pParkinS65 mediated mitophagy, pParkinS65 binds to PARIS, catalyzing its ubiquitination and proteasomal degradation, thereby alleviating its transcriptional repression of PGC1α and NRF2 and promoting mitochondrial biogenesis. Furthermore, evidence indicates that NRF2 transcriptionally regulates PINK1 expression during oxidative stress and amplifies mitophagy. Therefore, we hypothesize that mitochondrial turnover mechanisms can be regulated by targeting PARIS. In the present study, primary hASM cells were isolated from bronchiolar tissue of 6 patients with no history of chronic pulmonary disease or smoking. The hASM cells were phenotyped and separated into two treatment groups: 1) FCCP (1 µM, 6 h; positive control), a proton ionophore that induces mitochondrial depolarization (damage); 2) untreated control. We observed that FCCP induced extensive mitochondrial membrane depolarization, assessed by changes in mitochondrial membrane potential (Ψm) using TMRM (250 nM). Increased mitochondrial damage was observed with FCCP, measured by the extent of co-labeling of MitoTracker Red FM (200 nM) and CellLight Mitochondria-GFP. Mitochondrial turnover was also quantified by confocal imaging of hASM cells transfected with pMitoTimer, a fluorescent reporter protein in which fluorescence shifts over time from green (Excitation/Emission-488 nm/518 nm) to red (Excitation/Emission-543 nm/572 nm) when oxidized due to mitochondrial stress. Ratiometric analysis of pMitoTimer revealed significant shift from green to red fluorescence with FCCP and accumulation of pure red fluorescent puncta indicative of damaged mitochondria. FCCP increased PINK1 recruitment to mitochondria and increased pParkinS65 and ubiquitin (pUbS65) phosphorylation. Total PARIS accumulation decreased due to increased PARIS ubiquitination, as measured by immunoprecipitation. As a result, PGC1α and downstream NRF2 mRNA and protein expression, as well as mtDNA copy number were increased, indicative of increased mitochondrial biogenesis. Bioinformatics analysis and chromatin immunoprecipitation (ChIP) assay using an NRF2-specific antibody revealed that NRF2 binds to the promoter of PINK1, with FCCP further increasing the binding, thereby increasing PINK1 expression and enhancing mitophagy. Together, these findings identify the PARIS-NRF2 axis as a promising target to mitigate oxidative stress and maintain mitochondrial homeostasis in hASM cells. Supported by NIH grants HL157984 (GCS) and AG44615 (GCS) This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.