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Aging Cell

Human cells in long-term culture mirror features of aging

Experiments in four female fibroblast lines tracked molecular changes that resembled key features of aging in cells from the body.

Paper by Larissa Traxler, Lukas Karbacher, Oliver Borgogno, 10 more authorsJérôme Mertens · Department of Neurosciences University of California San Diego La Jolla California USA
Graphical abstract from Aging Cell
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Graphical abstract. Traxler et al., CC BY
Experiments in 4 human skin fibroblasts from female donors, 6 monthsInterventions

Limit: Uncorrected tests in the smaller comparison cohort could inflate apparent overlap in aging pathways

Edited by Boris Djordjevic · AgingResearch.News

Paper
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Researchers studied four female human fibroblast lines—connective tissue cells grown in the lab—in an experiment that maintained the cells long-term after they stopped dividing. Repeated analyses of gene activity and epigenetic patterns—features that affect gene activity without altering the DNA sequence—revealed key signatures of fibroblast aging in the body.

Individual cells became more varied in their biological age over time. Directly converting aged fibroblasts into nerve cells preserved their biological age. When the team tested compounds in the fibroblast system, metformin broadly reduced aging-related changes in gene activity and epigenetic patterns. Rapamycin showed limited effects on these measures. The authors presented the system as a platform for evaluating potential anti-aging compounds.

Why it matters

Following human cellular aging experimentally remains challenging. The authors propose that this platform could help researchers study aging mechanisms and evaluate candidate interventions for age-related diseases.

Caveats

These were laboratory cell experiments, so changes in molecular aging measures do not establish health or lifespan benefits. The paired molecular analyses involved four female fibroblast lines.

Where the evidence stands

Metformin

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.

  • 515 independent labs in 65 countries
  • 237 findings against
  • 1,476 trials, 628 with no results posted
  • Funders: National Institutes of Health and others
  • 172 of 2,398 findings with company ties
  • 195 of 1,476 trials sponsored by its developers

Rapamycin

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.

  • 298 independent labs in 47 countries
  • 97 findings against
  • 537 trials, 174 with no results posted
  • Funders: National Institutes of Health and others
  • 153 of 1,598 findings with company ties
  • 53 of 537 trials sponsored by its developers

From the paper

Result

A paired comparison of predicted age difference over 5 months in vitro revealed a significant difference in epigenetic and transcriptomic age gained, with a gain of 3.6 epigenetic years (95% CI [−1.0, 8.2]) and 21.5/10.4 transcriptomic years (95% CI [5.8, 37.2]/[4.9, 15.9]) (Figure 1h).

Results, 2.2 In Vitro Aging Accelerates DNAm and RNA Aging Clock Velocities

Limitation

This manuscript is primarily aimed at evaluating the extent to which a long-term in vitro culture model can recapitulate key features of human aging, rather than identifying novel aging pathways.

4 Limitations of the Study

Quoted word for word from the full text on onlinelibrary.wiley.com.

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Metformin is part of Bryan Johnson's Blueprint and David Sinclair's daily regimen in Lifespan

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