Qin Ma, PhD, FAIMBE, Dongjun Chung, PhD, and Mauricio Rojas, MD, have received a five-year, $3.2 million R01 grant from the National Institute on Aging at the National Institutes of Health (NIH) to study how senescent cells drive lung aging and age-related lung disease.
The research study, titled “Computational Identification and Experimental Validation of Senescent Cells and Signature Genes in Lung Aging and Diseases,” will identify and characterize senescent cells in aging human lungs and in idiopathic pulmonary fibrosis (IPF), a fatal disease of aging, to open new avenues for earlier diagnosis and treatment of IPF and related diseases.
IPF is the prototypical age-related lung disease, and will cause progressive scarring of the lungs and eventually, respiratory failure. A key driver is cellular senescence, a state in which damaged cells permanently stop dividing yet remain active, releasing inflammatory and pro-fibrotic signals that harm neighboring tissue. Senescent cells accumulate as the lungs age, and in IPF they accumulate earlier and in greater numbers, which suggests that the disease reflects accelerated lung aging. Because senescent cells are rare, diverse and difficult to study, it has been challenging to identify reliable biomarkers of the senescent state and to link them to tissue function and disease.
This study assembles a strong team of specialists in omics data analysis, deep learning tools development, statistical modeling, lung aging and fibrosis research and pulmonary science. Combining AI with advanced single-cell and spatial omics technologies, the team will pinpoint where senescent cells arise in aging lungs and lungs with IPF, how these senescent cells interact with neighboring cells and which signature genes distinguish normal lung aging from disease. Expected outcomes include:
- New single-cell and spatial omics datasets from aging and fibrotic human lungs.
- Novel deep learning and statistical tools to detect rare senescent cells and their signature genes.
- Experimental validation of candidate senescent cells and signature genes, i.e., Senotype.
- A foundation for senotherapeutics, treatments that selectively clear or reprogram senescent cells, for IPF, other age-related lung diseases and aging-related diseases in other organs.
By revealing how senescent cells shape the aging lung, this interdisciplinary research could help shift the current standard of care for IPE from treating late-stage lung disease to preventing or slowing it, supporting healthier lung aging for a growing older population.
