AgingResearch.NewsJoin free
Aging Cell

A protein helped limit aging-related changes in stem cells

Experiments in stem cells found that increasing a protein preserved the structure of their DNA-containing nuclei and counteracted senescence, a state in which cells stop dividing.

Paper by Ke Cheng, Yaru Wang, Yueyuan Pan, 12 more authorsXiaoling Zhou · Stem Cell Research Center Shantou University Medical College Shantou China
Graphical abstract from Aging Cell
Open the figure at full size
Graphical abstract. Cheng et al., CC BY
Experiments in cellsMechanisms

Limit: Senescence staining used a subjective endpoint: completion depended on observing several blue cells

Edited by Boris Djordjevic · AgingResearch.News

Paper
Follow

Experiments in mesenchymal stem cells, which can develop into several tissue cell types, examined how TOP2A, a protein that helps resolve twists in DNA, affected senescence. The researchers found that TOP2A levels progressively fell in senescent cells.

Depleting TOP2A reduced levels of Lamin B1, a protein that supports the nucleus, the cell’s DNA-containing compartment. It also caused rupture of the membrane surrounding the nucleus, disrupted heterochromatin—tightly packed DNA—and accelerated senescence. The researchers reported that TOP2A directly regulated production of Lamin B1. Increasing TOP2A restored Lamin B1 levels, reduced the loss of nuclear proteins, preserved nuclear integrity and counteracted senescence.

Why it matters

The authors point to the organization of DNA as a potential focus for research aimed at age-related cellular decline.

Caveats

The main evidence came from cell experiments, not studies in people. The abstract’s mouse finding involved inhibiting TOP2A, not showing benefits from increasing it.

Where the evidence stands

TOP2A

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.

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

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

  • 2 independent labs in 1 country
  • 10 trials, 5 with no results posted
  • Funder: Natural Science Foundation of Jiangxi Province
  • 9 of 10 trials sponsored by developers of drugs on it

LMNB1

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.

  • 25 independent labs in 15 countries
  • 1 finding against
  • Funders: National Institutes of Health and others
  • 2 of 32 findings with company ties

Comments

Be the first to comment.

More on Cellular senescence