Approach.
Approach.Epigenetic clocks are validated biomarkers of aging.
The methylation pattern on genomic DNA changes in a conserved way as organisms age.
Steve Horvath, whose research lies at the intersection of several fields including epigenetic biomarkers of aging, preclinical and clinical studies, genomics and epidemiology, showed that specific methylation sites could be used to predict the chronological age across most tissues in the human body with unprecedented accuracy.
Epigenetic clocks have become the most widely used aging biomarker in the field with close to 7000 citations. (1)
OSKM.
The Yamanaka Factors.
Discovered in 2006, the Yamanaka factors (OSKM) are a group of four genes known to rejuvenate the epigenetic clock in multiple cell types, and have been shown to extend the lifespan of mouse models.
This gene combination has not been translated into a rejuvenation therapeutic as it activates a tumor-inducing pluripotency pathway that poses serious safety concerns for its use in a therapeutic setting.
By omitting oncogene C-Myc from OSKM to leave OSK, researchers have been able to double the remaining lifespan of already aged mice (2) with OSK now being advanced to clinical trial to restore age-linked loss of vision (3). Despite these promising developments, the therapeutic window of OSK remains unclear given its pluripotency legacy.
Platform.
Platform.CLOCKWORK.
Discovery Platform
UMAP plot of scRNAseq data used to train the AC3 single cell aging clock.
Shift has pioneered a next-generation discovery platform built around two large-scale proprietary datasets:
- A multiomic observational dataset, enabling the training of our high throughput single cell aging clock (AC3) that is highly correlated with validated DNAm aging clocks (1)
- An scRNAseq perturbation dataset for training virtual cell models.
Using these powerful datasets, we have been able to train machine learning tools that allow us to identify promising targets for cell rejuvenation with unprecedented speed and precision, streamlining centuries of real-world experiments into months.
SB000.
The SB000 Breakthrough for Safer Cell Rejuvenation.
Identified in 2025 (4), Shift’s discovery of SB000 was a groundbreaking development for cell rejuvenation therapeutics.
SB000 is a rejuvenation gene selectively expressed in early development, capable of rejuvenating epigenetic clocks across cell types by 3-10 years per month of over-expression. SB000 can be delivered as a gene therapy to address a wide range of indications, including age-related hearing loss and vision loss.
SB000 expression does not induce pluripotency with absence of iPSC colonies (white dotted lines).
SB000.
SB101.
SB101 is a dual purpose target.
Shift is investigating small molecule inhibitors of SB101 that could enable systemic cell rejuvenation and fibrosis attenuation.
