Evidence map›Paper›PMID 40841648›Full record

ArticleCell communication and signaling : CCS2025

Cisd2 delays atrial aging via a modulation of calcium homeostasis that mitigates atrial myopathy.

Chi-Hsiao Yeh, Zhao-Qing Shen, Li-Hsien Chen, Carol Seah, Tsai-Yu Tzeng, Chien-Yi Tung, Wen-Tai Chiu, Cheng-Heng Kao, Ting-Fen Tsai

Abstract read
In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. A probioticGut microbes · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Chi-Hsiao YehDepartment of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Zhao-Qing ShenDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Li-Hsien ChenDepartment of Pharmacology, National Cheng Kung University, Tainan, Taiwan.
Carol SeahDepartment of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan.
Tsai-Yu TzengThe National Genomics Center for Clinical and Biotechnological Applications, Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Chien-Yi TungThe National Genomics Center for Clinical and Biotechnological Applications, Cancer and Immunology Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Wen-Tai ChiuDepartment of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan. wtchiu@mail.ncku.edu.tw.
Cheng-Heng KaoCenter of General Education, Chang Gung University, Taoyuan, Taiwan. kao@mail.cgu.edu.tw.
Ting-Fen TsaiDepartment of Life Sciences and Institute of Genome Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan. tftsai@nycu.edu.tw.

Funding

Chang Gung Memorial Hospital CMRPG3K2241National Health Research Institutes NHRI-11A1-CG-CO-07-2225-1, NHRI-12A1-CG-CO-07-2225-1, NHRI-13A1-CG-CO-07-2225-1 and NHRI-14A1-CG-CO-07-2225-1National Health Research Institutes NHRI-EX112-11239SINational Science and Technology Council MOST110-2314-B-182A-113-MY3National Science and Technology Council MOST 110-2320-B-A49A-529-MY3 and NSTC 112-2320-B-A49-011-MY3
6 · The paper itself

Abstract

Age-associated atrial myopathy results in structural remodeling and a disturbance of atrial conductance. Atrial myopathy often precedes atrial fibrillation (AF) and can facilitate AF progression. However, the molecular mechanism linking aging to atrial deterioration remains elusive. CDGSH iron-sulfur domain-containing protein 2 (CISD2) is a mammalian pro-longevity gene. We used Cisd2 knockout (Cisd2KO) and Cisd2 transgenic (Cisd2TG) mice to investigate pathophysiological mechanisms underlying age-related atrial myopathy. Four findings are pinpointed. Firstly, in both humans and mice, the level of atrial CISD2 declines during natural aging; this correlates with age-associated damage, namely degeneration of intercalated discs, mitochondria, sarcoplasmic reticulum (SR) and myofibrils. Secondly, in Cisd2KO and naturally aged wild-type mice, Cisd2 deficiency causes atrial electrical dysfunction and structural deterioration; conversely, sustained Cisd2 levels protect Cisd2TG mice against age-related atrial myopathy. Thirdly, Cisd2 plays a vital role in maintaining Ca²⁺ homeostasis in atrial cardiomyocytes. Cisd2 deficiency disrupts Ca²⁺ regulation, leading to elevated cytosolic Ca²⁺, reduced SR Ca²⁺, impaired store-operated calcium entry, and mitochondrial Ca²⁺ overload; these compromise mitochondrial function and attenuate antioxidant capability. Finally, transcriptomic analysis reveals that Cisd2 protects the atrium from metabolic reprogramming and preserves into old age a transcriptomic profile resembling a youthful pattern, thereby safeguarding the atrium from age-related injury. This study highlights Cisd2's crucial role in preventing atrial aging and underscores the therapeutic potential of targeting Cisd2 when combating age-associated atrial dysfunction, which may lead to the development of strategies for improving cardiac health in aging populations.

Indexed as

AgingCalciumHeart AtriaHomeostasisAnimalsHumansMaleMembrane ProteinsMiceMice, KnockoutMice, TransgenicMitochondriaMyocytes, CardiacSarcoplasmic ReticulumCalciumCISD2 protein, humanMembrane ProteinsAgingAtrial fibrillationAtrial myopathyCalcium homeostasisCisd2

Identifiers

PMID40841648
PMCPMC12369199

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.