Many world firsts here: first use of aging clocks in clinical trials, the first drug to reverse many independent aging clocks, and the first AI-generated drug for an AI-discovered target in phase 3
A small question: if a treatment changes fibrosis-related biology and several proteomic “aging clocks” move with it, how do we know that the clocks are measuring aging itself rather than a changing disease state?
Dominika, excellent article! I just watched your ARDD2025 presentation and thought it was very insightful! I'm sharing some links that I think you might find interesting.
The NAMPT increase buried in the protein list is the detail I'd want to chase further. NAMPT is the rate-limiting enzyme in the NAD+ salvage pathway, the same enzyme NMN and NR supplementation is trying to support indirectly. Seeing it come up alongside SOD2 and ALDH1A1, both stress-resistance and antioxidant enzymes, suggests TNIK inhibition might be doing something to NAD+ regeneration capacity that's independent of the senescence and fibrosis story the paper centers on. That would be a genuinely unexpected cross-link between TGF-beta/fibrosis biology and the NAD+ decline pillar of aging, two literatures that don't talk to each other much. Given that the clock signal plateaus at week 4 while several of these metabolic proteins were, per your read, still developing, it seems worth asking in the phase 3 data whether NAD+-pathway markers specifically keep moving past week 4 even after the composite clock score flattens out. If so that would argue the plateau is a clock-sensitivity artifact rather than the underlying biology stalling.
A small question: if a treatment changes fibrosis-related biology and several proteomic “aging clocks” move with it, how do we know that the clocks are measuring aging itself rather than a changing disease state?
Dominika, excellent article! I just watched your ARDD2025 presentation and thought it was very insightful! I'm sharing some links that I think you might find interesting.
https://youtu.be/Aj6pvAxWJyA
https://www.lifebiosciences.com/our-platform/targeting-the-biology-of-aging/
https://www.techbuzz.ai/articles/r3-bio-raises-funding-to-grow-brain-free-organ-systems
https://www.sciencefocus.com/the-human-body/freezing-brain-back-to-life
Congratulations! Human data with aging biomarkers is exactly what the field needs right now.
The NAMPT increase buried in the protein list is the detail I'd want to chase further. NAMPT is the rate-limiting enzyme in the NAD+ salvage pathway, the same enzyme NMN and NR supplementation is trying to support indirectly. Seeing it come up alongside SOD2 and ALDH1A1, both stress-resistance and antioxidant enzymes, suggests TNIK inhibition might be doing something to NAD+ regeneration capacity that's independent of the senescence and fibrosis story the paper centers on. That would be a genuinely unexpected cross-link between TGF-beta/fibrosis biology and the NAD+ decline pillar of aging, two literatures that don't talk to each other much. Given that the clock signal plateaus at week 4 while several of these metabolic proteins were, per your read, still developing, it seems worth asking in the phase 3 data whether NAD+-pathway markers specifically keep moving past week 4 even after the composite clock score flattens out. If so that would argue the plateau is a clock-sensitivity artifact rather than the underlying biology stalling.