Summary

We analyzed 850,000 single-cell transcriptomes of hematopoietic stem cells (HSCs) across ages and identified lead target genes for rejuvenation. This proposal aims to validate these targets in vitro using RNA-based interventions and small molecules.

Problem

Aging drives HSC dysfunction, impairing the regeneration of blood and immune cells. Current treatments lack strategies to restore youthful HSC function. Precise targets for rejuvenation remain unvalidated despite advances in scRNA-seq.

Impact

Validated interventions could reverse HSC aging, restoring regenerative capacity and immune balance. This work opens a new path for regenerative medicine, enabling multi-modal strategies to improve healthspan and combat age-related decline.

Background

VitaSTEM is the first AI-enabled longevity project and inaugural IP-Token launched by Aubrai, VitaDAO's decentralized scientific agent. After six months of deep research on public and proprietary single-cell RNA-seq and multi-omics datasets, the team analyzed more than 850,000 human hematopoietic stem cell transcriptomes from donors aged 23–91.

This effort uncovered 100+ high-potential rejuvenation target genes and revealed critical drivers of decline such as RhoA hyperactivation, CD38 upregulation, and CCR9 downregulation. Rather than treating HSC aging as a single defect, Aubrai recognized it as convergent damage across interconnected systems, generating a comprehensive multi-modal, five-phase rejuvenation protocol targeting transcriptional stress, metabolic dysfunction, and epigenetic drift in parallel.

Roadmap

Q3 2025 ✓ In-silico study
Identification of genes which have potential for in-situ HSC rejuvenation by human single cell RNA-seq data analysis.

Q4 2025 — In-vitro validation
Validate shortlisted target genes/proteins in in-vitro HSC cells.

Q2 2026 — Intervention studies
Perform gene activation/inhibition to confirm efficacy of the intervention in human Hematopoietic stem cells.

Q3 2026 — Small-molecule/drug intervention
Identify small molecules that can activate/inhibit to mimic targeted interventions.

Q4 2026 — Pre-clinical testing
Complete additional tests such as Toxicity studies, effective dose studies, etc., in mice and platforms such as human-on-a-chip.