Cell type-specific modulation of healthspan by Forkhead family transcription factors in the nervous system
Ekin Bolukbasi, Nathaniel S. Woodling, Dobril Ivanov, Jennifer Adcott, A. Reghan Foley, Arjunan Rajasingam, Lauren M. Gittings, Benjamin Aleyakpo, Teresa Niccoli, Janet M. Thornton, Linda Partridge
Abstract
Significance Aging is the main risk factor for the costliest diseases in today’s world. However, significant gaps remain in understanding how different cell types modulate this most common physiological process. Here, we use published single-cell gene expression data to map the prolongevity roles of two evolutionarily conserved Drosophila transcription factors, FKH and FOXO, onto either neuronal or glial cells. We then demonstrate that neuronal FKH preserves healthy function even under stress. Finally, we identify an autophagy-related gene as one of FKH’s downstream prolongevity effectors. Our results exemplify tapping into publicly available gene expression datasets to extract physiological insights, and highlight the need to shift away from organism-wide approaches and toward cell type-specific strategies to obtain meaningful insights in aging research.