Project Grant R01AG096197

The National Institute on Aging awarded $648,930 to the Regents of the University of California, doing business as University of California, Berkeley, on August 15, 2026, under the Aging Research program (CFDA 93.866) to develop human stem cell-based microphysiological systems for aging research.

The recipient will create a novel human aging-on-a-chip platform integrating fat and liver tissues derived from human induced pluripotent stem cells (hiPSCs) and microfluidics using serum from young versus old human donors of both sexes. The work addresses limitations of current animal models and human peripheral blood samples in studying aging of critical internal organs and the influences of genetic and functional diversity on human aging patterns. Under the first aim, the recipient will identify which hallmarks of aging can be generated in the on-chip tissues and determine their biological age using heterochronic microfluidics. The second aim involves developing sex-specific transcriptome-based age-predictor machine learning models for human white adipose tissue and liver, leveraging these models to identify aging biomarkers and correlate sex-specific expression signatures between in vitro and in vivo aging. The third aim uses the multi-tissue platform to establish age-related dysfunctions, then test young human serum and multiple pharmacological approaches for their ability to rejuvenate the system while identifying drivers of biological diversity in the rejuvenation response with respect to cell types, sex, genetics of hiPSC lines, and characteristics of serum donors.

The period of performance runs from August 15, 2026, through April 30, 2031, with work performed in Berkeley, California.