Yes… Mianserin is mechanistically intriguing, but its off target profile and safety concerns above make it a controversial longevity candidate.
To me, the most conceptually elegant molecule on the calcium-aging axis is ARM210 / S48168.
It targets leaky ryanodine receptors, aiming to restore proper calcium compartmentalization rather than simply blocking calcium signaling.
If RyR leak drives mitochondrial Ca2+ overload, ROS, and cellular dysfunction with age, then stabilizing RyR may help push cells back toward a younger functional state.
Thanks for this post.
Q. would it be helpful and feasable to run an analysis on British Biobank data and get survival analysis for persons using or having used mianserin, mirtazepin or fluvoxamin for prolonged time and compare those with matched age controls?
Probably death by suicide should be excluded assuming that risk to be lower in people striving for longevity.
My goodness how the Nature Communications standards have fallen. Letting people publish the headline-grabbing 17% lifespan extension based on 7 mice per group
I have been on low-dose 10 mg Mianserin for 30 years, for one wonderful effect It lets me fall asleep right after night-time urination. No side effects noticed. Intriguing if there could be some longevity aspect on top.
One long-term goal of aging research is to find drugs that can delay aging and the onset of age-associated diseases. With this in mind, we screened 88,000 chemicals for the ability to increase the lifespan of Caenorhabditis elegans nematodes. We found that mianserin, a serotonin receptor antagonist used as an antidepressant in humans, can increase C. elegans lifespan when given only during adulthood.
Using Caenorhabditis elegans as a model, we show that extending lifespan by inhibiting serotonergic signals by the antidepressant mianserin attenuates transcriptional drift, allowing the preservation of a younger transcriptome into an older age. Our data are consistent with a model in which inhibition of serotonergic signals slows age-dependent physiological decline and the associated rise in mortality levels exclusively in young adults, thereby postponing the onset of major mortality.
Relevant human trials are urgently needed to validate its anti-aging efficacy. Given that consistent lifespan extension has already been demonstrated in both nematodes (C. elegans) and mice, Mianserin would be a strong candidate for inclusion in the next ITP cohort. @RapAdmin
Yes, but the issue is that in mice it was delivered via IP injection and the ITP only takes orally delivered drugs (and there seem to be lots of potential issues regarding first pass metabolism and ultimate bioavailability of Mianserin in mammals). I’ll do an ITP proposal next year, but I could see it being rejected because of these issues.
The biotransformation and excretion of the antidepressant mianserin were studied after oral administration of the labelled drug to rats, mice, rabbits, guinea pigs and humans. Mianserin was well absorbed and almost completely metabolized in all five species.
Pts receiving M (and CT or BSC) had significantly better OS (p=0,0012). CT treated pts receiving M had significantly better survival comparing to those not receiving M (p=0.0015). BSC treated pts receiving M had also significantly better survival than those without M (p=0.003). M treated pts subgroups had significantly higher scores of QLQ-C30 and LC13 i.e. better HRQoL as well. (M:Mianserin)
I didn’t take it for depression. It was a bet by my doc that 10 mg would put me back to sleep after urination in the night. Works beautifully. An hour’s more sleep, instead of a battle to get back to sleep.I hardly remember having been up.
Calcium signaling and nitric oxide are deeply intertwined in biology… but paper stays strictly on the S100A6–PARP1–cGAS-STING pathway inside cells…
Good longevity research often starts narrow (like this paper) but then expands in follow-ups or in the broader field. This study is valuable because it gives a druggable entry point (calcium homeostasis via an old, cheap drug), but it is important to understand that it is only that, “one” entry point among many.
In my opinion, the adverse effects are particularly risky for older adults. The combination of sedation, orthostatic hypotension (raising fall/fracture risk), and the rare but serious agranulocytosis makes it far from ideal for long-term use. No human data.
Dang, I have been complaining on these board forever that I can’t sleep after I wake up to pee and not even melatonin helped me at all.
Do you take it at the time you wake up to pee, or do you take it before bed (and still helps you sleep), basically what time of day/night you take it? I desperately need to order it. Thanks,
Plus do any of you guys know if it’s available from India?
I take the Mianserin half to one hour before going to bed. It probaby helps me fall asleep I think it prevents occasional insomnia, but the main thing is that I do my peeing in the night without waking up. I have a stainless steel jug my bed, easily cleaned. In the morning it´s largely filled, from the water of the 1.2 kilos of veggies and berries that I consume in the evening before. I may be peeing up to three times a night I don´t know since I don´t remember. Once in a while I forget to take the Mianserin and my night is wrecked. When travelling it´s the one essential thing, together with my passport, to have along. I am forever indebted to the doc who was creative to think outside the box and prescribed it for me.
I get it prescribed here in Sweden. It´s commonly available as an anti-depressant and anxiolytic.
