UC San Diego Engineer Awarded Hypothesis Fund Grant to Explore Aging in Brain and Heart Cells

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Why do some of the body’s most important cells — like those in the brain and heart — age, even though they never divide? Zeinab Jahed, a professor in the Aiiso Yufeng Li Family Department of Chemical and Nano Engineering at the University of California San Diego Jacobs School of Engineering, has received a seed grant from the Hypothesis Fund to help answer this question.

While most research on the biology of aging has focused on cell division, cells such as neurons and cardiomyocytes do not divide. Yet, they show some of the earliest and most damaging signs of aging. Jahed suspects that these changes may stem from progressive weakening of the nuclear membrane — the barrier that protects a cell’s DNA.

A new project led by Jahed will put this idea to the test. The team will use nanotechnology developed in Jahed’s lab to trigger and study tiny ruptures in the nuclear membrane in real time.

The technology consists of an array of nanosized pillars that can delicately and precisely breach the cell nucleus without damaging the rest of the cell.  When a cell is placed on top of this array, its nucleus wraps around the pillars, creating local curvatures in the nuclear membrane. The curvatures induce tiny, self-sealing ruptures to temporarily form in the nuclear membrane. Researchers can then observe how well live cells can repair these ruptures, and whether that ability declines with age.

Using this tool, the team will study neurons and cardiomyocytes derived from established aging models at UC San Diego. They will measure how often nuclear ruptures occur; how quickly they are repaired; and how these events affect DNA damage, protein localization and cell survival. Comparing young and old cells will provide the first quantitative link between age and nuclear membrane integrity in post-mitotic tissues.

The findings could reshape how scientists understand aging at the cellular level. Instead of viewing nuclear damage as a byproduct of aging, it could represent one of its root causes — especially in long-lived cells that cannot renew themselves.

This project is supported by the Hypothesis Fund, which aims to advance scientific knowledge by backing early-stage, innovative research before preliminary data exist. The Fund targets bold ideas in basic research that might otherwise remain unpursued or underfunded through traditional channels.