How prelamin A and ZMPSTE24 contribute to premature aging
Using mouse models to dissect the roles of ZMPSTE24 and prelamin A in accelerated aging
This work looks at how a faulty protein called prelamin A and the enzyme ZMPSTE24 drive rapid aging, aiming to help people with progeria-like conditions.
Quick facts
| Grant type | R03 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Columbia University Health Sciences NIH-funded |
| Lab location | 1 site (New York, United States) |
| Project ID | NIH-11124880 on NIH RePORTER |
What this research studies
The team uses specially engineered mice that carry a human-like Lmna mutation causing permanently farnesylated prelamin A. They compare these LmnaL648R mice to mice lacking ZMPSTE24 to understand why one model shows milder, later-onset aging while the other has severe, early progeroid features. Researchers examine tissues, cell nuclei, and molecular changes to trace how prelamin A damages cells and organs over time. The goal is to pinpoint pathways that cause premature aging and to identify potential targets for future therapies.
Who could benefit from this research
Good fit: People with Hutchinson-Gilford progeria syndrome (HGPS), mandibuloacral dysplasia type B (MAD-B), or other disorders linked to prelamin A processing would be most relevant to follow or benefit from this research.
Not a fit: Patients whose aging issues are unrelated to prelamin A or ZMPSTE24 mutations are unlikely to see direct benefits from this mouse-focused project in the short term.
Why it matters
Potential benefit: If successful, this work could reveal mechanisms and targets that lead to new treatments for progeria-like disorders and inform strategies for aspects of normal aging.
How similar studies have performed: Related mouse models and interventions targeting prelamin A processing, such as farnesyltransferase inhibitors, have produced partial benefits, but the specific LmnaL648R model and the planned comparisons represent a relatively new approach.
Where this research is happening
New York, United States
- Columbia University Health Sciences — New York, United States (Active)
Researchers
- Principal investigator: Worman, Howard J — Columbia University Health Sciences
- Study coordinator: Worman, Howard J
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.