Evidence map›Paper›PMID 34324543›Full record

ArticlePloS one2021

Aging increases senescence, calcium signaling, and extracellular matrix deposition in human airway smooth muscle.

Sarah A Wicher, Benjamin B Roos, Jacob J Teske, Yun Hua Fang, Christina Pabelick, Y S Prakash

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Aging, brain-derived neurotrophic factor, and allergen-induced pulmonary responses in mice.American journal of physiology. Lung cellular and molecular physiology · 2025
    Article
  6. Review
  7. Article
  8. Unveiling mechanisms of lung aging in COPD: A promising target for therapeutics development.Chinese medical journal pulmonary and critical care medicine · 2024
    Review
  9. Endoplasmic reticulum stress-induced senescence in human lung fibroblasts.American journal of physiology. Lung cellular and molecular physiology · 2024
    Article
  10. Article
  11. Article
  12. Non-Genomic Hallmarks of Aging-The Review.International journal of molecular sciences · 2023
    Review
  13. Age-associated differences in the human lung extracellular matrix.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  14. Review
  15. The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023
    Article
  16. Basic Science Perspective on Engineering and Modeling the Large Airways.Advances in experimental medicine and biology · 2023
    Article
  17. Pim-1 kinase is a positive feedback regulator of the senescent lung fibroblast inflammatory secretome.American journal of physiology. Lung cellular and molecular physiology · 2022
    Article
  18. Article
  19. Cellular senescence is increased in airway smooth muscle cells of elderly persons with asthma.American journal of physiology. Lung cellular and molecular physiology · 2022
    Article
  20. Virus-Induced Membrane Fusion in Neurodegenerative Disorders.Frontiers in cellular and infection microbiology · 2022
    Review
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

6 authors at 2 institutions in 1 country.

Sarah A WicherDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America.ORCID 0000-0002-0079-7924
Benjamin B RoosDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America.
Jacob J TeskeDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America.ORCID 0000-0002-3361-5859
Yun Hua FangDepartment of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN, United States of America.
Christina PabelickDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America.ORCID 0000-0002-4632-2174
Y S PrakashDepartment of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN, United States of America.ORCID 0000-0002-2968-224X
Mayo Clinic · USMayo Clinic in Florida · US

Funding

Neurotrophins in the LungR01HL088029 · NHLBI · MAYO CLINIC ROCHESTER · PI PRAKASH, Y. S. · 2009 to 2022
$5.9M
Nicotine, Airway Smooth Muscle and AsthmaR01HL142061 · NHLBI · MAYO CLINIC ROCHESTER · PI PABELICK, CHRISTINA MARIA, PRAKASH, Y. S. · 2019 to 2022
$2.0M
NHLBI NIH HHS R01 HL088029NHLBI NIH HHS R01 HL142061
6 · The paper itself

Abstract

Lung function declines as people age and their lungs become stiffer. With an increasing elderly population, understanding mechanisms that contribute to these structural and functional changes in the aging lung is important. Part of the aging process is characterized by thicker, more fibrotic airways, and senile emphysema caused by changes in lung parenchyma. There is also senescence, which occurs throughout the body with aging. Here, using human airway smooth muscle (ASM) cells from patients in different age groups, we explored senescence pathways and changes in intracellular calcium signaling and extracellular matrix (ECM) deposition to elucidate potential mechanisms by which aging leads to thicker and stiffer lungs. Senescent markers p21, γH2AX, and β-gal, and some senescence-associated secretory proteins (SASP) increased with aging, as shown by staining and biochemical analyses. Agonist-induced intracellular Ca2+ responses, measured using fura-2 loaded cells and fluorescence imaging, increased with age. However, biochemical analysis showed that expression of the following markers decreased with age: M3 muscarinic receptor, TRPC3, Orai1, STIM1, SERCA2, MMP2 and MMP9. In contrast, collagen III, and fibronectin deposition increased with age. These data show that senescence increases in the aging airways that is associated with a stiffer but surprisingly greater intracellular calcium signaling as a marker for contractility. ASM senescence may enhance fibrosis in a feed forward loop promoting remodeling and altered calcium storage and buffering.

Indexed as

AgingCalcium SignalingCellular SenescenceExtracellular MatrixMyocytes, Smooth MuscleAdultAgedAged, 80 and overCalciumCalcium ChannelsCells, CulturedFemaleFibronectinsHumansLungMaleCalciumCalcium ChannelsFibronectinsNeoplasm ProteinsORAI1 ProteinORAI1 protein, humanReceptor, Muscarinic M3STIM1 protein, humanStromal Interaction Molecule 1TRPC3 cation channelTRPC Cation Channels

Identifiers

PMID34324543
PMCPMC8321097
OpenAlexW3185364303

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.