ArticleExperimental gerontology2014
Dysfunctional survival-signaling and stress-intolerance in aged murine and human myocardium.
Article in Experimental gerontology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
34 citing papers in PubMed, 61 citations in OpenAlex.
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- Isoflurane and Surgical Stress Disrupt Fatty Acid and Carbon Metabolism Leading to Cardiomyopathy.bioRxiv : the preprint server for biology · 2025Article
- Individual and Comorbid Influences of Chronic Stress and a Western Diet on Allostatic Loads and Cardiac Resilience, Adaptation and Proteome Profiles in Male Mice.Comprehensive Physiology · 2025Article
- Dysfunctional mitochondria elicit bioenergetic decline in the aged heart.The journal of cardiovascular aging · 2024Article
- Considering impact of age and sex on cardiac cytoskeletal components.American journal of physiology. Heart and circulatory physiology · 2024Review
- Remifentanil but not sufentanil induces cardioprotection in human ischemic heart muscle in vitro.BMC pharmacology & toxicology · 2023Article
- Defective dimerization of FoF1-ATP synthase secondary to glycation favors mitochondrial energy deficiency in cardiomyocytes during aging.Aging cell · 2022Article
- Reversing mitochondrial defects in aged hearts: role of mitochondrial calpain activation.American journal of physiology. Cell physiology · 2022Article
- Constitutive activation of ERK1/2 signaling protects against myocardial ischemia via inhibition of mitochondrial fragmentation in the aging heart.Annals of translational medicine · 2021Article
- Ageing, sex, and cardioprotection.British journal of pharmacology · 2020Review
- Targeting ER stress and calpain activation to reverse age-dependent mitochondrial damage in the heart.Mechanisms of ageing and development · 2020Review
- Dietary α-Linolenic Acid Counters Cardioprotective Dysfunction in Diabetic Mice: Unconventional PUFA Protection.Nutrients · 2020Article
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- Hurdles to Cardioprotection in the Critically Ill.International journal of molecular sciences · 2019Review
- Conditioning-induced cardioprotection: Aging as a confounding factor.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2018Review
- Hypoxia-derived exosomes induce putative altered pathways in biosynthesis and ion regulatory channels in glioblastoma cells.Biochemistry and biophysics reports · 2018Article
- The Effects of Aging on the Regulation of T-Tubular ICa by Caveolin in Mouse Ventricular Myocytes.The journals of gerontology. Series A, Biological sciences and medical sciences · 2018Article
- Caveolins as Regulators of Stress Adaptation.Molecular pharmacology · 2018Review
- Connexins and Nitric Oxide Inside and Outside Mitochondria: Significance for Cardiac Protection and Adaptation.Frontiers in physiology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Changes in cytoprotective signaling may influence cardiac aging, and underpin sensitization to ischemic insult and desensitization to 'anti-ischemic' therapies. We tested whether age-dependent shifts in ischemia-reperfusion (I-R) tolerance in murine and human myocardium are associated with reduced efficacies and coupling of membrane, cytoplasmic and mitochondrial survival-signaling. Hormesis (exemplified in ischemic preconditioning; IPC) and expression of proteins influencing signaling/stress-resistance were also assessed in mice. Mouse hearts (18 vs. 2-4 mo) and human atrial tissue (75±2 vs. 55±2 yrs) exhibited profound age-dependent reductions in I-R tolerance. In mice aging negated cardioprotection via IPC, G-protein coupled receptor (GPCR) agonism (opioid, A1 and A3 adenosine receptors) and distal protein kinase c (PKC) activation (4 nM phorbol 12-myristate 13-acetate; PMA). In contrast, p38-mitogen activated protein kinase (p38-MAPK) activation (1 μM anisomycin), mitochondrial ATP-sensitive K(+) channel (mKATP) opening (50 μM diazoxide) and permeability transition pore (mPTP) inhibition (0.2 μM cyclosporin A) retained protective efficacies in older hearts (though failed to eliminate I-R tolerance differences). A similar pattern of change in protective efficacies was observed in human tissue. Murine hearts exhibited molecular changes consistent with altered membrane control (reduced caveolin-3, cholesterol and caveolae), kinase signaling (reduced p70 ribosomal s6 kinase; p70s6K) and stress-resistance (increased G-protein receptor kinase 2, GRK2; glycogen synthase kinase 3β, GSK3β; and cytosolic cytochrome c). In summary, myocardial I-R tolerance declines with age in association with dysfunctional hormesis and transduction of survival signals from GPCRs/PKC to mitochondrial effectors. Differential changes in proteins governing caveolar and mitochondrial function may contribute to signal dysfunction and stress-intolerance.
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