Ever looked into SR9009 or SR9011? They’re implicated in circadian clock modulation. It might be of interest to you.
I just posted a deep dive on the studies on both of these: Anyone Tried Various Modulators of Circadian Systems? - #3 by AustraliaLongevity
GPT analysis on the potential longevity implications of doubling REM sleep without increasing sleep duration:
What REM amplification drugs like BMB-101 could mean for longevity
• Sleep becomes an active rejuvenation platform, not just recovery
Doubling REM without increasing sleep time means the brain gets far more neural repair, emotional detoxification, and synaptic optimization every night. This turns sleep into a nightly cognitive rejuvenation cycle rather than just downtime.
• Chronic stress and inflammation would be structurally reduced
REM sleep is where the brain shuts off norepinephrine and processes emotional memory. More REM means less baseline stress signaling, lower cortisol, and less systemic inflammation, all of which are core drivers of aging.
• Neurodegeneration risk would likely drop
REM supports synaptic pruning, network reorganization, and metabolic waste clearance in the brain. Enhancing it could slow or prevent processes involved in Alzheimer’s, Parkinson’s, and age related cognitive decline.
• Mental health and biological aging are tightly linked
Depression, anxiety, PTSD, and burnout all suppress REM and accelerate aging. By restoring REM, you attack both psychological suffering and the biological wear and tear that comes with it.
• Learning, plasticity, and skill retention would stay youthful
REM is where new memories, motor skills, and abstract patterns are consolidated. Maintaining high REM across decades means preserving the brain’s ability to adapt, which is one of the strongest predictors of long term cognitive health.
• Sleep efficiency increases instead of sleep duration
Longevity is not just about sleeping more. It is about sleeping better. Converting light, low value sleep into high value REM is like upgrading the quality of nightly cellular maintenance without increasing time spent unconscious.
• This fits perfectly into a “Sleep 2.0” model
A drug like BMB-101 would be one component of a future system that combines pharmacology, wearables, environment control, and biological feedback to turn every night into a targeted rejuvenation session.
• This is the kind of intervention that compounds for decades
One good night helps. Ten thousand optimized nights could reshape aging trajectories. REM amplification is the rare lever that could quietly produce massive gains over a lifetime.
I can’t find any more announcements from this womans profile or the organization she works for but apparently the molecule they were working with was called Harmine.
- Sleep deprivation leads to alterations in mitochondrial health and a protein complex known as DREAM.
- Harmine, which blocks DREAM, mitigates the cellular aging triggered by sleep deprivation.
- Blocking DREAM allows cellular repair genes, such as antioxidant genes, to be activated.
What is harmine?
GPT analysis:
In the Context of Sleep and Aging
In the sleep deprivation study you referred to, harmine is being tested not for its traditional neuropharmacology but for its ability to block components of the DREAM complex, enabling repair gene activation in conditions where sleep is insufficient. That is a distinct molecular angle from its roles as a MAO-A or DYRK1A inhibitor and speaks to emerging research on cellular aging pathways.
Bottom line:
Harmine is a multifunctional natural alkaloid with a long traditional history, multiple molecular targets in the nervous system, and a emerging experimental role in cellular repair pathways. Early research suggests both potential benefits and dose-dependent risks, but it remains far from validated as a therapeutic in humans outside of tightly controlled studies.
To me this indicates harmine could be another worthy candidate for ITP testing, and certainly for improving sleep which I believe is one of the main levers we will end up using for meaningful lifespan extension.
I recently put my genome into Claude.ai and followed it’s recommendations for longevity given my genetic vulnerabilities - citicholine 500mg + lecithin 1200mg + creatine 3g + lithium orotate 5mg + magnesium threonate and bisglycinate+ glycine 3g.
Four days later and i slept 10 hours with vivid dreams for the first time in a couple of years.
I’ve since had 10 days of good sleep with no waking or easy fall back to sleep. Dreams nightly. Average sleep time has increased by almost an hour.
Ok, I was avoiding this so I didn’t keep spending money, but now @L_H you have me interested in getting this info…
I’m sure it’[s been discussed, but what are the least expensive ways to get our genome?
The problem. Sleep is the most rejuvenating process we have, but it isn’t fully restorative. Biological age markers still accumulate despite good sleep. One underexplored lever: sleep’s rejuvenating power isn’t fixed, and its main waste-clearance mechanism has an identified upstream regulator that may be pharmacologically targetable.
The mechanism. The glymphatic system clears interstitial waste (beta-amyloid, tau, metabolic byproducts) via CSF-interstitial fluid exchange through perivascular channels, dependent on astrocytic AQP4 water channels. Flow is gated by norepinephrine tone: elevated NE during wake shrinks extracellular space and blocks exchange; NE decline during NREM sleep expands the space and lets flow proceed. Locus coeruleus output is the controlling structure.
Proof of concept: dexmedetomidine. This alpha-2 agonist hyperpolarizes LC neurons, cutting norepinephrine release, and produces EEG slow-wave activity resembling natural NREM sleep. Preclinical work shows it enhances glymphatic clearance, restores AQP4 localization, and is being studied for reducing postoperative cognitive dysfunction. It’s also been shown to enhance glymphatic delivery of intrathecal drugs, confirming it opens the CSF-ISF pathway pharmacologically. Caveat: it works by inducing sleep-like unconsciousness, not by decoupling flow from arousal. It’s ICU/anesthesia-only for good reason (bradycardia, hypotension). This is proof of mechanism, not a usable intervention.
Guanfacine: plausible, unconfirmed. Guanfacine is a weaker, more selective alpha-2A agonist used at non-sedating doses (0.5-4mg) for ADHD and hypertension, working mainly on postsynaptic PFC receptors rather than producing LC-driven unconsciousness. No study directly measures its effect on glymphatic clearance. The inference that it partially engages the same pathway is mechanistically plausible (same target, same direction on NE tone) but unconfirmed. Its sedation side effect is circumstantial support, not evidence.
Open question for the piece: Is there a dose/selectivity sweet spot between “too weak to matter” (possibly guanfacine) and “full sedation” (dexmedetomidine) that could deepen or extend the NE-trough during actual sleep, without acting as a daytime sedative? Nobody appears to have tested this.
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