Aging-Related Myocardial Susceptibility Lowers Cardiac Tolerance to Chronic Intermittent Hypoxia Through Dynamin-Related Protein 1-Associated Mitochondrial Vulnerability.
Y, S., Y, M., J, T., F, W., & Q, Z. (2026). Aging-Related Myocardial Susceptibility Lowers Cardiac Tolerance to Chronic Intermittent Hypoxia Through Dynamin-Related Protein 1-Associated Mitochondrial Vulnerability.. Aging cell. https://doi.org/10.1111/acel.70684
Y S, Y M, J T, F W, Q Z. Aging-Related Myocardial Susceptibility Lowers Cardiac Tolerance to Chronic Intermittent Hypoxia Through Dynamin-Related Protein 1-Associated Mitochondrial Vulnerability.. Aging cell. 2026; doi: 10.1111/acel.70684
Y S, Y M, J T, et al. Aging-Related Myocardial Susceptibility Lowers Cardiac Tolerance to Chronic Intermittent Hypoxia Through Dynamin-Related Protein 1-Associated Mitochondrial Vulnerability.[J]. Aging cell. 2026. DOI: 10.1111/acel.70684.
@article{y2026,
author = {Su Y and Miao Y and Tan J and Wang F and Zhang Q},
title = {Aging-Related Myocardial Susceptibility Lowers Cardiac Tolerance to Chronic Intermittent Hypoxia Through Dynamin-Related Protein 1-Associated Mitochondrial Vulnerability.},
journal = {Aging cell},
year = {2026},
doi = {10.1111/acel.70684},
note = {PMID: 42642787},
}
TY - JOUR AU - Su Y AU - Miao Y AU - Tan J AU - Wang F AU - Zhang Q TI - Aging-Related Myocardial Susceptibility Lowers Cardiac Tolerance to Chronic Intermittent Hypoxia Through Dynamin-Related Protein 1-Associated Mitochondrial Vulnerability. T2 - Aging cell PY - 2026 DO - 10.1111/acel.70684 AN - PMID:42642787 ER -
Chronic intermittent hypoxia (CIH), a cardinal pathophysiological feature of obstructive sleep apnea (OSA), repeatedly exposes the heart to hypoxia-reoxygenation stress. The cardiac outcome of CIH, however, may depend on the biological state of the target myocardium. Here, we investigated whether a pre-existing aging-related myocardial susceptibility lowers the tolerance threshold for CIH-induced injury and whether Dynamin-related protein 1 (Drp1) contributes to the enhanced vulnerability of senescence-like cardiomyocytes under CIH. Using G3 Tert-deficient (Tert-/-) mice and D-galactose (D-gal)-induced senescence-like primary cardiomyocytes, we show that aging-related susceptibility consistently amplifies CIH-induced cardiac injury. In young wild-type mice, 8 weeks CIH induced early cardiac remodeling and senescence-associated myocardial stress without overt systolic decompensation. In Tert-/- mice, the same CIH exposure shifted the cardiac response further toward maladaptive remodeling. Compared with CIH alone, EF and FS were reduced by an additional 24.6% and 15.8%, respectively. In senescence-like cardiomyocytes, CIH amplified mitochondrial vulnerability, with impaired energy production, elevated mitochondrial oxidative stress, and a fission-biased mitochondrial dynamics marker profile. Drp1 knockdown did not fully reverse this mitochondrial state but restored 55.1% of the CIH + D-gal induced ATP decline and reversed 47.4% of the mitochondrial ROS excess, while attenuating DNA damage response activation and senescence-associated signaling. These findings indicate that aging-related myocardial susceptibility is not a passive contextual factor in CIH-induced injury but a biological state that actively shapes the cardiac response to repeated hypoxia-reoxygenation stress. Drp1-associated mitochondrial dynamics imbalance may represent a functional link between diminished mitochondrial stress tolerance and amplified cardiomyocyte vulnerability.