Altos Labs, backed by extensive funding, acquires Stanford spinout Dorian Therapeutics to integrate its epigenetic senoblockers into a cellular rejuvenation program. The deal unites Dorian’s chromatin-modulating approach for targeting senescent cells with Altos Labs’ reprogramming platform, aiming to reduce age-related tissue damage and enhance regenerative capacity across multiple organ systems.
Key points
Altos Labs acquires Dorian Therapeutics to bolster its cellular rejuvenation pipeline.
Dorian’s small-molecule senoblockers modulate epigenetic regulators to reduce senescent cell burden.
Preclinical efficacy shown in lung fibrosis and osteoarthritis models enables in vivo reprogramming strategies.
Why it matters:
This acquisition combines epigenetic senescence targeting with reprogramming platforms, accelerating the translation of cellular rejuvenation therapies to clinical applications.
Q&A
What are senescent cells?
How do senoblockers differ from senolytics?
What challenges exist for epigenetic reprogramming in vivo?
Why is targeting cellular senescence crucial for longevity?
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Academy
Cellular Senescence and Senotherapeutics
Cellular senescence is a state of permanent growth arrest that cells enter in response to stressors such as DNA damage, oxidative stress, or telomere shortening. While this mechanism protects against malignant transformation, the accumulation of senescent cells over time contributes to chronic inflammation and age-related tissue dysfunction through the secretion of pro-inflammatory cytokines, chemokines, growth factors, and proteases collectively known as the senescence-associated secretory phenotype (SASP).
Researchers have identified two main therapeutic strategies to address senescence in aging and disease:
- Senolytics: Agents that selectively induce apoptosis in senescent cells, physically removing them from tissues.
- Senomorphics or Senoblockers: Compounds that suppress or modulate the SASP to reduce harmful inflammatory signals without eliminating the cells.
Senoblockers are designed to target key signaling pathways that regulate the SASP, such as the NF-kB pathway, p38 MAPK, and mTOR signaling. By dampening the secretion of pro-inflammatory factors, senoblockers can restore tissue homeostasis and improve regeneration while avoiding the potential drawbacks of senescent cell clearance. Common molecular targets include JAK/STAT signaling, BMP pathways, and epigenetic regulators that control chromatin accessibility.
Preclinical models have demonstrated that senoblockers can ameliorate a variety of age-related conditions. For example:
- Lung Fibrosis: Senoblocker treatment reduces collagen deposition and improves lung function in mouse models by attenuating inflammatory fibrosis.
- Osteoarthritis: Intra-articular injection of senoblockers in rodents decreases joint inflammation and cartilage degradation.
- Metabolic Disorders: Systemic administration of senoblockers improves insulin sensitivity and reduces adipose tissue inflammation in aged mice.
Delivery methods for senoblockers include oral formulations, injectable nanoparticles, and targeted antibody conjugates to achieve effective tissue distribution. Challenges remain in balancing efficacy, safety, and long-term tolerability, but ongoing clinical trials are exploring combinations of senolytics and senomorphics for synergistic effects.
Future directions involve integrating senotherapeutics with partial epigenetic reprogramming techniques to rejuvenate tissue function more comprehensively. Advances in single-cell omics, AI-driven drug discovery, and biomarker development will further refine senescence-targeting strategies and enable personalized interventions in human aging.
