In January 2026, their work published: Sengstack et al. Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation, PNAS, 2026

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.

They found four unique transcription factors that could each independently restore cellular aging hallmarks. Two were via overexpression, and two were via repression. This is the first study to demonstrate single-target repression can cause rejuvenation.

“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.

UCSF posted an article covering the publication, including some beautiful images by Dr. Sengstack from her research.

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.

We look forward to bringing the first programs from the RESET Platform, inspired by this breakthrough research, to human clinic trials.

Please see the full PNAS research article here: https://doi.org/10.1073/pnas.2515183123

Things are progressing rapidly at Junevity. We are building a future where cell reprogramming for all major tissues enables far longer healthspan and lifespan. The ongoing data from our first drug program supports the feasibility and promise of our approach.

As demonstrated in preclinical studies, Junevity’s JUN_01 is the first known candidate to reprogram metabolism to a healthier, younger state. The effects include reduced blood glucose, improved insulin sensitivity, weight loss and maintenance of lean mass, all with the infrequent dosing and safety benefits enabled by siRNA. JUN_01 engages a novel, confidential target identified from the Junevity RESET platform, human disease data and genetic linkages. This target is implicated as a principal regulator of chronic metabolic dysfunction, insulin signaling and appetite. Preclinical models suggest best-in-class efficacy potential, low side effects, dosing once every six months and resistance to weight bounce back after treatment is ended. JUN_01 is promising as a monotherapy and in combination with GLP-1s and could enable lower or less frequent doses of GLP-1s. First-in-human trials are expected to begin in the second half of 2026.

The median age in the U.S. is now 38.5 years. This means more than half of the U.S. is middle-aged and aging (two of our three founders included!). Father Time remains undefeated. We aim to change this, starting with healthspan and lifespan-extending drugs in metabolism and neurodegeneration, and ultimately cell reprogramming for all major tissues.

Coverage: First Word Pharma, Axios, Longevity.Technology, LinkedIn

Today is another step towards longer, healthier lives.

It all started back in 2017 when Janine’s PhD advisor at UCSF, Dr. Hao Li, asked her, “I have an idea for a PhD project for you to lead… but it’s high risk. Would you be interested?”

With much hesitation, Janine said, “Yes!”

Today, we are thrilled to announce Junevity has raised our first $10M of VC Seed funding to develop Cell Reset therapeutics for longevity. Our science and platform is based on Janine’s PhD work with Hao and the Li Lab.

We make siRNA therapeutics targeting transcription factors. This approach is powerful. Transcription factors regulate broad-based gene expression. Targeting transcription factors with therapeutics can lead to reversing cellular damage caused by aging and disease. Breakthroughs in genomics, AI and siRNA make this possible. In fact, this only was possible to even consider during Janine’s PhD from 2017-2023.

We’ve all experienced the suffering, pain and loss of age-related disease in people close to us. We believe science, AI and human ingenuity can fix this.

John and Rob are both second-time founders, with John’s first company earning FDA approval for Trudhesa for migraines and Rob’s successfully acquired by FranklinCovey (NYSE: FC). When looking for their next venture, they both wanted a big idea that could change the future of human health.

Junevity is that idea.

You can read more about our funding announcement here, as well coverage from Longevity.Technology (here) and Endpoints News (here, paywall).

Please consider following us and sharing the news on LinkedIn or X (@Junevity).