The biologist Stephen Treaster examines a zebrafish tank in the lab.

By using rockfish and zebrafish, Stephen Treaster hopes to understand how to extend animal lifespans.

Credit: Michael Goderre, Boston Children’s Hospital

New genetic pathways involved in aging

By analyzing the changing genomes of short- and long-lived rockfish, scientists identified a new set of genes that might alter lifespan.
Dan Samorodnitsky
| 4 min read
Register for free to listen to this article
Listen with Speechify
0:00
4:00

There is no complete genetic explanation for why humans live longer than mice or why tortoises can live for a century. Looking for answers in long-lived animals’ genomes is tempting for researchers who want to figure out which genes extend lifespan. 

“I want to live as long as possible,” said Stephen Treaster, a postdoctoral researcher at Boston Children’s Hospital. “I want to see what technology and society looks like in 1000 years, ideally”he said. Treaster used rockfish as an unlikely organism to explore the possibilities for longevity and uncovered two new pathways that appear connected to lifespan. He and his colleagues published their results in Science Advances (1).

For aging studies, researchers mostly use short-lived animals like mice, which live about three years, or Drosophila and Caenorhabditis elegans, which live for months or days (2–4). “To make them live 10, 15, 20 percent longer, it doesn't necessarily apply to our end of the aging spectrum,” said Treaster.  “Evolution has already solved the aging problem. There are individual species that can live hundreds and hundreds of years. My approach is to look at these exceptionally long-lived models.”

Lifespan arises in different species from a complex network of genes and environmental interactions. Because of that complexity, it is difficult to look at the genetics of many model organisms and say for certain which genes contribute to that organism’s lifespan. Fortunately, a natural evolutionary experiment on longevity exists. Rockfish are a family of common marine fish with worldwide distribution. Some species of rockfish live as little as 10 years while others can reach ages of 200 years or more. Since the rockfish clade emerged a relatively recent eight million years ago, there hasn’t been time for rockfish to develop much genetic diversity. 

A pink colored rockfish swims near a pink colored bubblegum coral.
The wide variety of lifespans in rockfish make them an interesting model for aging research.
credit: NOAA's National Ocean Service

The rockfish’s nascent lineage is an analyst’s advantage. The wide variety of lifespans that different rockfish lineages exhibit can easily be pinned to genetic differences. Just as important, rockfish lifespans do not correlate with environmental conditions such as temperature or water depth, the kind of confounding effects that might make a genetic link to longevity in other animals less clear. 

By analyzing genes related to aging that seemed to be evolutionarily selected across a variety of different rockfish species with varying lifespans, Treaster identified two different genetic pathways that seem to have evolved along with changes in lifespan. 

The first pathway controls insulin signaling. Scientists know that insulin signaling affects aging and metabolism from past studies in other model organisms. “On one hand, this is kind of a boring result,” said Treaster. On the other hand, however, the fact that insulin signaling reappeared when analyzing rockfish seems to confirm the group’s approach.

It was extremely clever analysis. It's not an easy analysis to do because the genomes of these [fish] are not well described. 
Stephen Austad, University of Alabama

The other less  well-known pathway they found is in the flavonoid signaling network. The flavonoid pathway is made up of proteins with activity modulated by flavonoid molecules, which are three-ring and 15-carbon structures common in plants (5). 

“None of the previous mouse or fly studies have pointed to the flavonoid network,” said Steven Austad, an evolutionary biologist and aging researcher at the University of Alabama at Birmingham who was not involved in the study.  “It was extremely clever analysis. It's not an easy analysis to do because the genomes of these [fish] are not well described.”

While Treaster is excited about identifying a possible new genetic link to lifespan, he emphasized that how exactly flavonoid pathway genes affect lifespan is not known. “The next step is to play with these genes from rockfish to see if we can extend longevity in a conventional model. We're doing that right now. We are targeting these genes in zebrafish to see if we can extend lifespan,” said Treaster. If that work confirms that flavonoids do directly alter lifespan, then Treaster hopes that scientists interested in aging-related diseases may explore the pathway for potential drug targets.

Austad isn’t certain that identifying these genetic pathways to aging in fish will result in druggable targets in humans. He doubts that the insulin pathway, which has a demonstrated connection to longevity in flies and roundworms, can be connected to human lifespan. “The evidence that that's a major player in human aging is relatively sparse,” he said, noting that there haven’t been any human centenarians with identified novel mutations in the insulin signaling pathway. 

Nevertheless, the publication gave him hope. “This flavonoid network — it's really a new thing and deserves investigation,” he said.

References

  1. Treaster, S. et al. Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation. Sci Adv  9, eadd2743 (2023).
  2. Van Voorhies, W. A. & Ward, S. Genetic and environmental conditions that increase longevity in Caenorhabditis elegans decrease metabolic rate. Proc Natl Acad Sci USA  96, 11399–11403 (1999).
  3. Paaby, A. B. & Schmidt, P. S. Dissecting the genetics of longevity in Drosophila melanogasterFly  3, 29–38 (2009).
  4. Blüher, M., Kahn, B. B. & Kahn, C. R. Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue. Science  299, 572–574 (2003).
  5. Chen, L. et al. Intracellular signaling pathways of inflammation modulated by dietary flavonoids: The most recent evidence. Critical Reviews in Food Science and Nutrition  58, 2908–2924 (2018).

About the Author

  • Dan Samorodnitsky
    Dan earned a PhD in biochemistry from SUNY Buffalo and completed postdoctoral fellowships at the USDA and Carnegie Mellon University. He is a freelance writer whose work has appeared in Massive Science, The Daily Beast, VICE, and GROW. Dan is most interested in writing about how molecules collaborate to create body-sized phenomena.

Related Topics

Loading Next Article...
Loading Next Article...
Subscribe to Newsletter

Subscribe to our eNewsletters

Stay connected with all of the latest from Drug Discovery News.

Subscribe

Sponsored

Gold circles with attached purple corkscrew shapes represent gold nanoparticles against a black background.

Driving gene therapy with nonviral vectors 

Learn why nonviral vectors are on the rise in gene therapy development.
A 3D digital illustration of a viral spike protein on a cell surface, surrounded by colorful, floating antibodies in the background

Milestone: Leapfrogging to quantitative, high throughput protein detection and analysis

Researchers continuously push the boundaries of what’s possible with protein analysis tools.
Blue cancer cells attached to a cellular surface against a bright blue background in a 3D rendering of a cancer infection.

Advancing immuno-oncology research with cellular assays

Explore critical insights into immunogenicity and immunotoxicity assays for cancer therapies.
Drug Discovery News November 2024 Issue
Latest IssueVolume 20 • Issue 6 • November 2024

November 2024

November 2024 Issue

Explore this issue