Believes best approach is tissue maintenance and repair (not trying to prevent the damage).
Young people suffer the same damage as old people, but they have better repair mechanisms.
Younger healthier tissues are impossible without everything at cellular level being healthy.
Parabiosis in vitro - old blood dominates.
What is important in vivo?
50% plasma replacement (saline + 5% albumin) -> mice became statistically the same as young mice.
Old plasma dilution:
- reduces brain senescence
- reduces neuroinflammation (after single treatment)
- rejuvenates hippocampal neurogenesis
Compared performance to ABT263 senolytic.
Kiana Aran created a blood brain barrier (BBB) organ-on-a-chip device
- old blood perturbs BBB
Also tried young plasma dilution - did not become old - showed it isn't something in young blood that is needed.
Aging is driven by an excess of systemic proteins
- indispensable at young levels (can't just remove)
- removal of age-related proteins allows upregulation of youthful proteins
- recalibrating levels of proteins produces younger gene expression, therefore reducing epigenetic age
- younger proteome drivers younger transcriptome which drives younger epigenome
Q: Has an increased lifespan been observed?
A: Health extension is more important than life extension
Hard to do repeat procedures on mice (difficult procedure because of their size)
First impact is reduction in inflammaging, precipitates young faction.
Q: Why effect not seen in plasma donors?
A: Need to reboot system by donating ~70% at a time - more than donated - must reach a threshold to obtain positive feedback
Q: Any update on human TPE trials?
A: Was a pilot study - not full blown clinical trial. Results are promising so fund-raising a phase 3 trial.
Q: Is there an age beyond which it won't work?
A: Don't think so - mice were equivalent of 80, and have 90 year old in study