ArticleProceedings of the National Academy of Sciences of the United States of America2013
Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.
- The Dual Nature of Sinoatrial Node Remodelling in Athletes: A Systematic Review of Electrophysiological Adaptations and the Pathological Tipping Point.International journal of molecular sciences · 2025Pooled it
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- AMPK-mediated HCN4 channel phosphorylation contributes to age-related intrinsic bradycardia.The Journal of general physiology · 2026Article
- Evaluation of Dexmedetomidine-Associated Bradycardia and Related Drug-Drug Interactions Using Electronic Health Record (EHR) and miRNA Target Analysis.Current issues in molecular biology · 2025Article
- Extracellular activation of HCN4 by a subtype-specific nanobody.Nature communications · 2025Article
- Cardiac ageing: from hallmarks to therapeutic opportunities.Cardiovascular research · 2025Review
- Healthy ageing in older adults with cardiovascular disease.European heart journal · 2025Review
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Aging reduces the number and function of L-type calcium channels in the membrane of cardiac pacemaker cells.bioRxiv : the preprint server for biology · 2025Article
- Old and new equations for maximal and anaerobic threshold heart rate prediction in coronary heart disease in Chinese population.BMC cardiovascular disorders · 2024Article
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- The brain-body energy conservation model of aging.Nature aging · 2024Review
- Phosphorylation of cardiac sodium channel at Ser571 anticipates manifestations of the aging myopathy.American journal of physiology. Heart and circulatory physiology · 2024Article
- SanPy: Software for the analysis and visualization of whole-cell current-clamp recordings.Biophysical journal · 2024Article
- Circadian regulation of sinoatrial nodal cell pacemaking function: Dissecting the roles of autonomic control, body temperature, and local circadian rhythmicity.PLoS computational biology · 2024Article
- Identifying sex similarities and differences in structure and function of the sinoatrial node in the mouse heart.Frontiers in medicine · 2024Article
- Injection of IFrontiers in physiology · 2023Article
- The funny current If is essential for the fight-or-flight response in cardiac pacemaker cells.The Journal of general physiology · 2022Article
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- Cardiomyocyte-Specific Long Noncoding RNA Regulates Alternative Splicing of the Triadin Gene in the Heart.Circulation · 2022Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
An inexorable decline in maximum heart rate (mHR) progressively limits human aerobic capacity with advancing age. This decrease in mHR results from an age-dependent reduction in "intrinsic heart rate" (iHR), which is measured during autonomic blockade. The reduced iHR indicates, by definition, that pacemaker function of the sinoatrial node is compromised during aging. However, little is known about the properties of pacemaker myocytes in the aged sinoatrial node. Here, we show that depressed excitability of individual sinoatrial node myocytes (SAMs) contributes to reductions in heart rate with advancing age. We found that age-dependent declines in mHR and iHR in ECG recordings from mice were paralleled by declines in spontaneous action potential (AP) firing rates (FRs) in patch-clamp recordings from acutely isolated SAMs. The slower FR of aged SAMs resulted from changes in the AP waveform that were limited to hyperpolarization of the maximum diastolic potential and slowing of the early part of the diastolic depolarization. These AP waveform changes were associated with cellular hypertrophy, reduced current densities for L- and T-type Ca(2+) currents and the "funny current" (If), and a hyperpolarizing shift in the voltage dependence of If. The age-dependent reduction in sinoatrial node function was not associated with changes in β-adrenergic responsiveness, which was preserved during aging for heart rate, SAM FR, L- and T-type Ca(2+) currents, and If. Our results indicate that depressed excitability of individual SAMs due to altered ion channel activity contributes to the decline in mHR, and thus aerobic capacity, during normal aging.
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