Peer-reviewed discovery platform and data in PNAS show that single transcription factor modulation reverses aging-associated gene expression and restores healthy cellular and tissue function in models aging
Findings establish the scientific foundation for Junevity’s RESET discovery platform for cell reprogramming and support development of siRNA therapeutics advancing toward first-in-human studies in 2026
SAN FRANCISCO--(BUSINESS WIRE)--#AI--Junevity, a biotechnology company on a mission to extend lifespan and healthspan with cell reprogramming, today announced the publication of a peer-reviewed study in Proceedings of the National Academy of Sciences (PNAS) validating that precise modulation of individual transcription factors can reverse core hallmarks of cellular aging and restore tissue function in vivo. The paper covers systemic identification of transcription factors for cell and tissue rejuvenation. The findings form the scientific foundation for Junevity’s RESET platform and longevity-focused therapeutic programs, including JUN_01, the company’s lead siRNA (silencing RNA) candidate for type 2 diabetes and obesity.
Junevity co-founders Dr. Janine Sengstack and Dr. Hao Li together at the University of California San Francisco (UCSF) set out to identify novel transcription factor targets for rejuvenation back in 2017. The study describes a data-driven framework developed at UCSF that integrates global transcriptomics, computational modeling and targeted genetic perturbations with CRISPR-based Perturb-seq to uncover transcriptional control points that drive cellular rejuvenation. Using this approach, the authors identified multiple single-factor perturbations that reversed hallmarks of aging in human cells and demonstrated tissue-level rejuvenation in vivo, without inducing dedifferentiation or oncogenic programs.
Utilizing a model of human fibroblast aging, the researchers identified four transcription factors individually capable of reversing age-associated gene expression programs across multiple cellular hallmarks including proteostasis, mitochondrial function and senescence. Importantly, the research also showed significant rejuvenation of livers in aged mice, marked by the reversal of aging-associated gene expression profiles, reductions in liver steatosis and fibrosis and improved glucose tolerance, indicating functional metabolic benefits.
“Our work at UCSF laid the groundwork for the platform and therapeutics we are developing at Junevity. This research, with the preprint in 2022, was the first to show that repressing a single transcription factor could rejuvenate cells. Single-target repression enables siRNA as a modality, significantly improving therapeutic translatability for cell reprogramming with once every 6-12 month dosing, low manufacturing costs and a strong safety profile," said Dr. Janine Sengstack, PhD, the co-founder and Chief Scientific Officer at Junevity and co-first author of the paper.
“We created a platform that demonstrates systematic discovery of novel rejuvenating targets. Its applications are broad for cell reprogramming and rejuvenation, and the platform approach can apply to many cell types, tissues and age-related diseases,” said Dr. Hao Li, a UCSF Professor of Biochemistry and Biophysics and Director of UCSF Hillblom Center for Biology of Aging.
Dr. Sengstack’s breakthrough research led to the founding of Junevity to bring siRNA reprogramming therapeutics to patients. The proprietary Junevity RESET platform uses omics, genetic linkages, machine learning and siRNA to unlock novel cell reprogramming targets for therapeutic development. Previously “undruggable,” this technology enables targeting of transcription factors, which are master regulatory genes.
Junevity’s lead program, JUN_01, engages a novel, confidential target identified by the Junevity RESET platform using human disease data, genetic linkages, and machine learning. Preclinical studies demonstrated that JUN_01 led to significant improvements in glucose control, insulin sensitivity, and body weight, supporting advancement toward first-in-human development for type 2 diabetes and obesity. The company is growing its initial pipeline of siRNA candidates in metabolism and neurodegeneration. Junevity’s long-term vision is to develop siRNA reprogramming for all major tissues implicated in complex disease to extend healthspan and longevity.
Please see the full PNAS research article here: https://doi.org/10.1073/pnas.2515183123
About Junevity
Junevity is a biotechnology company developing cell reprogramming therapeutics with siRNA. The Junevity RESET platform is the first to use human disease omics, genetic linkages and ML/AI to identify novel transcription factor targets and repress them with siRNA therapeutics. Initial programs are in metabolism and neurodegeneration. Based in San Francisco and founded out of UCSF in 2023, Junevity’s mission is to increase lifespan and healthspan. Learn more at junevity.com.
Contacts
Media:
Tim Ingersoll
Linnden Communications
tim@linndencom.com
