LSD1 (KDM1A) demethylates H3K4me1/2 via FAD-dependent oxidation — removing active enhancer/promoter marks and licensing transcriptional repression.
In the CoREST complex, it couples demethylation to HDAC1/2-mediated deacetylation for compounded silencing.
LSD1 inhibition extends lifespan in model organisms. The local H₂O₂ byproduct at demethylation sites may be a redox signal — the full mechanistic picture isn't resolved yet.
EZH2 (PRC2) trimethylates H3K27 → PRC1 recruitment → chromatin compaction → transcriptional silencing.
Elegant at the mechanistic level. Consequential at the organismal level — elevated EZH2 activity shortens lifespan in model organisms, likely via progressive silencing of stress-response loci.
The SET domain may be one of the most underrated targets in aging biology.
#EZH2 #PRC2 #Epigenetics #AgingBiology #H3K27me3 #ChromatinRemodeling #Longevity
Mitochondrial health = longevity foundation 🔋
Healthy mitochondria → efficient energy production + cellular protection
Dysfunction = nearly every age-related disease
Promising interventions: NAD+ precursors, mitophagy enhancers, targeted antioxidants
The question now: how do we translate this into effective therapies?
#Longevity #Mitochondria #AgingBiology #Healthspan #CellularBiology
New 30% mouse lifespan extension paper just dropped!
Another example of rapamycin + something increasing mouse lifespan more than rapamycin or something alone. In this case, the something is trametinib, an anti-cancer drug.
Read more here: https://andrewsteele.co.uk/blog/2025/05/rapamycin-trametinib-cocktail-lifespan-mice/
I had an amazing chat with Davina McCall (!!!) about ageing, menopause, how we could live to 90 in good health, and how much fun it is to give birth?!? (Her words not mine!)
Check it out her new podcast, Begin Again, for the full conversation :)
#aging #ageing #longevity #menopause #longevityscience #agingbiology
Current lab crew:
The new semester has begun, and we have welcomed a new student to the lab🤩
And, we we are already celebrating his birthday during his first week🎉🥳
#GraduateSchool #BiomedicalScience #CellBiology #MolecularBiology #Genetics #Biochemistry #CancerBiology #AgingBiology
A new paper in Nature Aging suggests age-related changed are nonlinear, and change is most rapid around ages 45 and 60.
As someone rapidly approaching the first, biggest hump: gulp!
They did thousands of measurements, and these graphs show how many change at different ages:
You can check out a video of the session here, and my question around 51 minute sums up my thoughts: https://www.weforum.org/open-forum/event_sessions/turning-back-the-clock-the-science-of-ageing/
All the #rapamycin trials in the news this month! This is looking at using it in ME/CFS: https://meassociation.org.uk/2023/11/rapamycin-pilot-treatment-trial-for-me-cfs/
The idea is that ME/CFS may be partly driven by dysfunctional autophagy (a process by which cells recycle waste), and rapa could help. Fascinating, I hope it works!
In a recent podcast, Peter Attia decried some coverage of aging biology as ‘sci-fi’, and said it was impossible to ‘biohack your way to 150’.
I think he’s right.
But I made a video about it because I think he’s missing something very important: https://youtu.be/cCOh8l2NEQg
Alice Frolov
Andrew Steele
Eishi Noguchi