The Treaster Lab

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Comparative Genomics of Longevity and Evolutionary-informed Solutions to Aging

Aging is a universal challenge for life, yet different species do so at wildly different rates and timings. Inherent to this variable trait is the linked ability to maintain heath and resist age-related diseases. While most species lose critical functionality in weeks, months, or a few years, some species are able to resist cancer, heart disease, and maintain neuromuscular function in an unforgiving wild for centuries. How this diversity has evolved and is regulated is a complete mystery. In short—why do some animals live longer than others?

Knowledge of these mechanisms would have untold value towards understanding and mitigating human aging, which remains the greatest risk factor for the diseases that plague modern society.

My lab taps into the natural diversity of lifespans across species and populations to identify shared genomic signatures, produced by evolution, to regulate those changes. This work includes generating and mining genomic data from exceptional species, as well as developing tools for their analysis and their intersection with diverse ‘omics resources, including human population variation. Shared evolutionary signatures underlying lifespan shifts are then tested and modeled in zebrafish to identify mechanisms that will extend healthspan. This research discovers and tests evolutionary solutions to aging, ultimately to inform treatments to delay age-related diseases in people.

Projects

Evolution of Exceptional Longevity in Rockfish and Humans

To resolve the genetic regulation of longevity, we have mined genomic variation in rockfishes, ranging in maximum lifespan from 11 to over 205 years. Multiple shifts in rockfish longevity have occurred independently, and in a short evolutionary time frame, empowering convergence analyses. Our analyses reveal a common network of genes under convergent restricted evolution in long-lived lineages. These include established aging regulators such as insulin-signaling pathways, yet also aromatic-hydrocarbon metabolism as a novel pathway modulating longevity. Further, these genes were used to refine human longevity GWAS, identifying the aromatic-hydrocarbon metabolism pathway to be significantly associated with human survival to the 99th percentile. This evolutionary intersection defines and cross-validates a novel, conserved genetic architecture that associates with the evolution of longevity across vertebrates.

Genetics and Genomics of the Longest-lived Animal

The ocean quahog, Arctica islandica, can survive for over five-hundred years off the coast of Iceland. However, 1000 miles away in the Baltic Sea, the same species survives for only 35 years. With collaborators from the Alfred Wegener Institute, we have generated a high-quality reference genome for Arctica islandica and sequenced individuals from the different populations. We are working to identify genomic controls that may be underlying the dramatic reduction in maximum longevity as the species proliferated into the Baltic Sea roughly 10,000 years ago. In parallel, we are comparing genomes across clam species of different lifespans, from 4 to 500 years, to find both population and species level signatures underlying changes in lifespan.

Evolution of Fleeting Lifespan in the Shortest-lived Vertebrate

Dwarf Gobies include the shortest-lived vertebrate known, surviving a mere 59 days in the wild. Due to high extrinsic mortality, they have been selected for rapid development and reproductive maturity with no investment in longevity. These lineages are a unique, natural case study in vertebrate genomics at the limits of life history possibilities, including the timing of development, reproduction, onset of aging, and maximum longevity. Importantly, intrinsic to these variable traits is also variable paces of aging and resistance to age-related disease. We have sequenced sixteen goby species, including eight in the short-lived Dwarf Goby clade, to compare across fishes and discover genomic controls that have accelerated their life history.

Zebrafish Modeling of Evolutionary Solutions to Aging

In order to capitalize on the evolutionary aging solutions identified in the above analyses, and to inform treatments to extend healthy aging in humans, they must first be tested to extend healthy aging in a lab model. The Treaster Lab is capitalizing on the zebrafish as a high-throughput, low-cost, genetically-amenable vertebrate as an experimental platform for aging research—a field that desperately needs new vertebrate models. This platform will enable timely assessment of genetic and chemical manipulations to modulate biological age in vertebrates, strengthening the likelihood of translational potency in humans. To enable this platform, we are establishing comprehensive healthspan and biomarker tests to accelerate aging mechanism validation and empower zebrafish labs worldwide to pivot their research towards aging with minimal investment.

Meet the Team

Collaborators 

Matthew Harris, Ph.D., The Harris Lab at Harvard Medical School and Boston Children’s Hospital

Michael MacArthur, Ph.D., Princeton

Yi Feng, Ph.D., Rockefeller University

Publications

See Dr. Treaster’s full list of publications here. 

Castro J., Fagerstrom, K., Treaster S., Duryea J., Charles J., Harris MP. The function and regulation of celsr1a in skeletal age-associated homeostasis and repair. Journal of Gerontology: Biological Sciences (2025). doi.org/10.1093/gerona/glaf091

Treaster S., Deelen J., Daane J., Murabito J., Karasik K., Harris MP. Convergent genomics of longevity in rockfishes highlights the genetics of human life span variation. Science Advances (2023). doi.org/10.1126/sciadv.add2743

Treaster S., Daane J., Harris MP. Refining Convergent Rate Analysis with Topology in Mammalian Longevity and Marine Transitions. Molecular Biology and Evolution (2021). doi.org/10.1093/molbev/msab226

Treaster S., Karasik, D., and Harris, MP. Footprints in the Sand: Deep Taxonomic Comparisons in Vertebrate Genomics to Unveil the Genetic Programs of Human Longevity. Frontiers in Genetics (2021). doi.org/10.3389/fgene.2021.678073

Peskin B., Henke K., Cumplido N., Treaster S, Harris M., Bagnat M., Arratia G. Notochordal Signals Establish Phylogenetic Identity of the Teleost Spine. Current Biology (2020). doi.org/10.1016/j.cub.2020.05.037

Li C, Barton C, Henke K, Daane J, Treaster S, Caetano-Lopes J, Tanguay RL, Harris MP. celsr1a is essential for tissue homeostasis and onset of aging phenotypes in the zebrafish. eLife (2020). doi.org/10.7554/eLife.50523

Treaster, S.B., Chaudhuri, A.R., Austad, S.N. Longevity and GAPDH Stability in Bivalves and Mammals: A Convenient Marker for Comparative Gerontology and Proteostasis. PLoS ONE (2015). doi.org/10.1371/journal.pone.0143680

Treaster, S.B., Ridgway, I.D., Richardson, C.A., Gaspar, M.B., Chaudhuri, A.R., and Austad, S.N. Superior proteome stability in the longest-lived animal. AGE (now GeroScience) (2014). doi.org/10.1007/s11357-013-9597-9

Zhang, Y., Bokov, A., Gelfond, J., Soto, V., Ikeno, Y., Hubbard, G., Diaz, V., Sloane, L., Maslin, K., Treaster, S., Rendon, S., van Remmen, H., Ward, W., Javors, M., Richardson, A., Austad, S., Fischer, K. Rapamycin extends life and health in C57BL/6 mice. J. Gerontol. A. Biol. Sci. Med. Sci. (2014). doi.org/10.1093/gerona/glt056

Sung, L.-Y., Chang, C.-C., Amano, T., Lin, C.-J., Amano, M., Treaster, S.B., Xu, J., Chang, W.-F., Nagy, Z.P., Yang, X., Tian, XC. Efficient derivation of embryonic stem cells from nuclear transfer and parthenogenetic embryos derived from cryopreserved oocytes. Cell. Reprogramming (2010). doi.org/10.1089/cell.2009.0072

Funding Sources

Massachusetts Department of Agricultural Resources

Massachusetts Life Sciences Center

Massachusetts Technology Collaborative

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