“My SPARK project aims to uncover how DNA modifications drive immune system decline with age. I will use cutting-edge technology to analyze T cell alterations across diverse age groups, ultimately revealing strategies to enhance immune function and prevent age-related diseases.”
2025 Tullie and Rickey Families Spark Awards Winner
Nirmalya Dasgupta, Ph.D.
Is the decline of immunity with age written in our DNA?
Funded: February 2025
Funded By: The generosity of LJI Board Director David Rickey and the Rickey Family
I have successfully collected peripheral blood mononuclear cells (PBMCs) from a diverse group of young and older adult donors, balanced by sex. I established reliable protocols for cell isolation, enrichment, and subset sorting, focusing particularly on CD8+ T cell populations. My investigation so far has revealed some key differences in how these cells work in younger versus older study participants. My work indicates that as people age, not only do they have fewer new, responsive CD8+ T cells, but a substantial fraction of their memory T cells also become “zombie-like” and less effective against infections and cancers. “Zombie” CD8+ T cells are also a problem because they can no longer divide or fight effectively, yet they persist and release signals that drive chronic inflammation.
These findings underscore a fundamental shift in the immune system’s landscape with aging and may explain reduced vaccine responses and impaired immune surveillance in older individuals. By pinpointing these shifts in T cell subsets, our study opens avenues for targeted interventions aimed at restoring functional CD8+ T cells. Such strategies could help rejuvenate the aging immune system, potentially enhancing resilience and promoting healthier aging.