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Aging Cell

Immune and scar-related signals cluster in aging mouse hearts

Gene activity maps from 6- and 24-month-old mice pointed to valves and the aorta as major sites of age-related immune and scar-related changes.

Paper by Aleksandra Aljakna Khan, Amalia Sintou, Yue Zhao, +11 more authorsNadia A. Rosenthal · The Jackson Laboratory Bar Harbor Maine USA
Graphical abstract from Aging Cell
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Graphical abstract. Aljakna Khan et al., CC BY

Our read

Mechanisms
Studied:
Cross-sectional study of male and female C57BL/6J mice, against other heart regions
What changed:
Immune and scar-related gene signals were concentrated in heart valves and the aorta rather than other heart regions
The catch:
Only 3 mice per sex and age group supported the spatial patterns
Why it’s aging research:
It studies organisms or tissues that aged naturally.

Editor of record: Boris Djordjevic · AgingResearch.News

Paper
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Male and female C57BL/6J mice aged 6 or 24 months were compared in an animal experiment, with three mice per sex at each age. The researchers measured gene activity across whole hearts and mapped it to cell types and locations.

Signals from macrophages, immune cells, and fibroblasts, cells that build tissue’s supporting material, were concentrated mainly in valves and the aorta, the body’s main artery. In older mice, macrophages showed gene activity changes linked to poorer immune regulation, attracting other cells and reshaping tissue. More widely distributed fibroblast-lineage cells showed changes in genes involved in organizing tissue’s supporting material and communication between cells. They also showed increased activity of a gene associated with senescence, a state in which cells stop dividing.

Why it matters

Age-related inflammation and tissue scarring can reinforce one another. Pinpointing where these processes meet may help clarify how this feedback loop affects the aging heart.

Caveats

Gene activity patterns do not by themselves show that the mapped changes caused scarring or impaired heart function. The comparison involved one mouse strain, with three animals per sex at each age.

Where the evidence stands

Cellular homeostasis

Mice: replicated by independent labs. Cells, worms or flies and humans: a single group.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 74 independent labs in 17 countries
  • 1 finding against
  • Funders: National Institutes of Health and others
  • 11 of 84 findings with company ties

Cellular senescence

Cells, worms or flies, mice and humans: replicated by independent labs.

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

No results posted: trials that ended over a year ago with no results on ClinicalTrials.gov and no paper reporting them.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

Includes the processes named after it and trials of drugs aimed at it.

  • 859 independent labs in 75 countries
  • 518 findings against
  • 51 trials, 15 with no results posted
  • Funders: National Natural Science Foundation of China and others
  • 663 of 9,875 findings with company ties
  • 49 of 51 trials sponsored by developers of drugs aimed at it

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