vamin
#73
Could you share a list of SNP ids that you think are important to check?
First, like rapamycin for longevity, neutrigenomics is also relatively new and still at the pre-scientific stage.
I’m returning to this thread after some time. I was asked where I found out about the SNPs. I got them from re-analysis of 23andMe raw data. 23andMe only analyzes about 15% of the genome so I wouldn’t recommend them. I’ve got a kit ordered from Dante. Periodically they have a $199 full genome analysis sales.
With the full genome, there will be a lot of problematic SNPs. The re-analysis programs will alert you to problem mutations.
Promethiase should have all the problematic mutations. I’m going to say mutations because my Android dictation does better with that word then using the acronym. It seems to be compiled for professionals so it can go into more detail than then I can understand. On the other hand, it won’t go into enough detail for us to understand if we’re not well educated in molecular biology. And maybe evolutionary biology too.
A previous post listed the reanalysis services that I used.
I found this website when we got started 10 or 12 years ago. It’s a great overview and it’s been extended quite a bit since last time I looked at it. It is from a for-profit medical practice so you’re not going to get the best deal on supplements from them. That said, they’ve been doing neutrogenomics for a long time and might be helpful.
There is a big learning curve, even for a professionals, so if you can find somebody with a lot of experience and you have money, it might be faster to work with a person like that then hacking it yourself. The hacking is fun but it can be slow and there may be some uncomfortable mistakes. It might depend upon how young you are and how much time you have.
https://heartfixer.com/AMRI-Nutrigenomics.htm
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I started selegiline June '23 at 1.25mg in the morning and ran out in April '24. While taking it I found more “clarity” of thought and more motivation. Re-ordered and started back at the same dose this week.
Have already noticed the motivation aspect has returned, pretty happy with that 
Our youngest son is 40 and was diagnosed with ADHD when he was 13. The Psychologist said it was “too late” to do much as he had already “adapted”. Quit school at 16, got a good union job in construction and bought his first house at 19. Then got lost/obsessed with an online game and quit work, eventually had to sell his house. He has struggled with a variety of interpersonal issues and could not hold down a job for very long. Smarter than the average bear, memory like a steel trap, incredibly ambitious, one of the hardest working men I’ve met, at least physically. Organized? not a chance but oddly, always finds the most efficient way to do what he needs to do. Authority? not into being told what to do LoL! and thus the job issues. May '22 he started his own junk removal and metal recycling business. And it’s going very well, getting lots of commercial business and enjoying being his own boss. Gets up at 4am to work out and then out making it happen by 5:30am. He’s a monster physically and loving all the peptides LoL!
He started on selegiline at 2.5mg in the morning the same time I did and ran out the same time and started back the same time. Last year, about 3 months in we were all out for dinner with some friends and without prompting he started talking about how much better he felt and how he was more able to organize his thoughts. He attributed this to the selegiline.
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LukeMV
#76
I ask Liner AI if Selegiline increases lifespan. Here was the answer.
The effects of low-dose selegiline on lifespan have been explored in various studies, indicating potential benefits in longevity.
Background on Selegiline
Selegiline, also known as (-)-deprenyl, is primarily recognized as a monoamine oxidase-B (MAO-B) inhibitor that is used in the treatment of Parkinson’s disease. Its mechanism relates to the enhancement of dopaminergic activity, which has sparked interest in its potential effects on aging and longevity .
Longevity Studies in Animals
Experiments have demonstrated that low doses of selegiline can lead to increased lifespan in certain animal models. A significant study published in 1988 reported that rats treated with MAO-B inhibitory doses of (-)-deprenyl lived significantly longer than their saline-treated counterparts . This finding has been corroborated by various subsequent studies, which consistently indicate a lifespan-extending effect.
Mechanism of Action
The proposed mechanism for the lifespan-extending effects of selegiline involves enhancing catecholaminergic activity. Research has shown that selegiline’s effects are dose-dependent, exhibiting both “specific” and “non-specific” enhancer effects at different dosages . The enhancement in learning ability in aged rats treated with low doses corroborates the notion that selegiline may positively influence age-related decline .
Comparative Potency
In comparative studies, it has been found that other enhancer substances, such as BPAP, may be more potent than selegiline in extending lifespan. Specifically, BPAP in lower doses achieved significant results in promoting longevity, suggesting that while selegiline has positive effects, its efficacy may not be as pronounced as that of certain newer substances .
Conclusion
The collective evidence suggests that low-dose selegiline may increase lifespan, particularly in laboratory animals, by enhancing dopaminergic function and mitigating age-related cognitive decline . However, further research is needed to explore the translation of these findings to human subjects and to fully elucidate the mechanisms involved.
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adssx
#77
Parkinson’s patients on selegiline don’t appear to live longer unfortunately. I still hope selegiline will succeed in the ITP…
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LukeMV
#78
So it is being tested in the ITP? I hope it does well since I’ve been taking 1.25mg for like 5 years now. The Parkinson’s patients might be using very high doses that aren’t ideal for life extension.
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adssx
#79
Yes selegiline = deprenyl: Suggestions for ITP drugs to test - #172 by LVareilles
Parkinson’s patients use 5 mg per day oral or 1.25 mg per day sublingual. So five times more than you.
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LukeMV
#80
lol, that was my own post from August but had forgotten all about it. Thanks
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We’ve been taking 1.25mg Selegiline every morning for close to 2 years now.
Since I’m nearly perfect anyways, it’s hard to tell if it’s made a difference LoL!
But our youngest son (40y/o) who has pretty high ADHD takes 2.5mg every day and after about 6 months offered his unsolicited opinion, “it’s working! and I find better focus and more clarity of thought”
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LukeMV
#82
You split the 5mg tabs into quarters I imagine? That’s what I do as well.
Although, I’ve seen some say it’s better to take sublingual. I’m not sure how accurate that is.
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adssx
#83
Sublingual is way more potent. 1.25 mg sublingual is like 5 mg orally from what I remember.
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Yep, sort of, 1/2 for the son and 1/4 each for the Boss and I so 1 tab per day.
adssx
#85
When you (or your son) don’t take selegiline (intentionally or because you forgot), did you notice any withdrawal/rebound symptoms?
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At the 1.25mg dose I don’t notice anything taking it nor if I miss a dose or 2.
Our son at 2.5mg does notice the effect and if he misses a dose.
A number of our interventions are “brain” focused
Occasionally, maybe a couple times a month I take 2.5mg but I don’t notice anything at that dose either. Since I don’t have a “condition” that this drug would technically benefit I never expected to notice much but was looking for “something” but nothing.
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adssx
#87
Thanks.
So you take it only for its purported longevity properties?
What are your other brain focused interventions?
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I’ve tried a couple nootropics but never noticed much.
Besides sleep, exercise and a decent diet we do a few things;
- a variety of basic supplements
- tVNS
- creatine
- selegiline
- caffeine
- microdose golden teacher 'shrooms a couple times a year
- low dose THC (oral)
- GLP1-R’s
- growth hormone secretagogues
- DHEA
- melatonin
Will be trying a few peptides in the New Year
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I’ve been taking it orally most days since I was in my fifties (late 60s now). Started off with 1/4 of a 5 mg tablet, gone up to 1/2 2.5mg after age 60. Don’t feel any different but am taking it on the evidence we have so far.
Just had a list of the normal NHS blood tests. Doc phoned up to give me the results, seemed slightly incredulous that everything was in normal range, except for too much testosterone.
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adssx
#90
A novel neuroprotective mechanism of selegiline by suppressing the pro-apoptotic activity of protein disulfide isomerase 2025
Beyond its role in MAO-B inhibition, selegiline exhibits neuroprotective effects, potentially through anti-apoptotic mechanisms. Recent studies have shown that selegiline can prevent mitochondria-dependent apoptosis [1], whereas the specific molecular targets for such effect remain elusive.
In summary, we leveraged selegiline’s unique N-propargylamine moiety for ABPP and identified PDI as a key target in our study. Selegiline covalently binds to PDI at residues S32, C56, and K207, notably within the catalytic CGHC motif at C56, thereby inhibiting PDI’s enzymatic activity. Typically, PDI plays a protective role in the unfolded protein response (UPR), but it can also exhibit pro-apoptotic functions in neurodegenerative diseases, leading to mitochondrial outer membrane permeabilization (MOMP) and cell death. Our findings reveal that selegiline-mediated inhibition of PDI prevents MOMP in isolated mitochondria and rescues ER stress-induced apoptosis in MN9D cells, thereby unveiling a novel aspect of its neuroprotective mechanism.
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Neo
#91
@adssx So perhaps on and off cycles of some short - would not want it to stop good apoptosis?
adssx
#92
I don’t know enough about this.
What I know is that selegiline 1.25 mg (1/4 of a pill) lifted my mild depression and apathy after a few weeks. I stopped after a month, and 2 months later my mental health is still great. (Why did I stop? It increased my blood pressure and I’m not sure about its long-term use. I also wanted to see if I could do without it and the test was successful.) So given its longevity + neuroprotection potential, low-dose selegiline might be the best antidepressant at least for mild symptoms? If my depression comes back I’ll try again selegiline (effectively cycling it as needed).
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