Nir Barzilai's ranked list of longevity compounds

#36

Our personal experience with sulphoraphane supplementation is quite amazing. I had read that it may help with Autism so I purchased some for our, at that time 4y/o autistic grandson. He is now 5.

He was non-verbal, no eye contact but was comfortable with a hug and a cuddle :slight_smile: some are not.

Within a week of taking 400mcg of Swanson Sulphoraphane in his morning juice, he changed dramatically. Eye contact, all the time, saying one or two words.

A year later, full sentences, says his alphabets, knows all his dinos, fully engaged and looks you straight in the eye. He is a very kind little boy and treats his little 3 y/o sister very well, even when she causes him trouble, he does not retaliate. She is on the spectrum as well but not as bad at her age as he was.

He is still autistic as this is not a “cure” but it sure makes a difference. When he misses a dose you can see it the next day. If he takes too much, he becomes overly emotional (sad scenes really bother him) when he is watching his fav TV show.

Dose makes a difference for him. It’s quite amazing.

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#37

As far as I understand, a sulforaphane supplement must contain both glucoraphanin and myrosinase. I looked up the label for the Swanson brand and it’s unclear if it contains both.

Last I checked, BROQ/protaphane and Avmacol (and perhaps Broccomax which is suspiciously cheap) are the only sulforaphane supplements that have both.

Since Broq is considered the gold standard but costs more than $1 per day to get a serving, I haven’t been taking it.

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#38

May i ask the sourcing for Retatrutide?

I didn’t managed to find out any commercial

Fabio

#39

Agree. On the other hand, hip fractures result in significant morbidity and mortality in the elderly. As a dentist, my advice is to only use these if you either have no teeth or super healthy teeth. If you’re on a bisphosphonate, there’s a risk of non-healing. If you really need bone density support, I’d recommend either Forteo (not used much as it’s pricey and a daily injection) or Prolia, which only lasts about 6 months, so any oral surgery is safe if timed properly with the infusions. Floss!!

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#40

Deborah_Hall, Osteoporosis is one of the things I’m concerned about. I always thought an adequate diet and exercise would resolve any problems for me until I got an osteopenia report years ago. I’ve avoided the bisphosphenates for the reasons you cite and I’ve found no solutions other than continuing my diet + exercise routine. Have you done any research on HGH or peptides that increase HGH in connection with bone heatlh? I speak from ignorance, but I do wonder if low-dose HGH (or HGH promoting peptides) would improve bone density the way it would naturally take place.

#41

Posted in the wrong thread. Here’s a great talk on bone health. Or just buy his book: Great Bones.

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#42

Hi Jay, you said that you found no solutions, and I think that we don’t have solutions, at least not a pharma silver bullet. Even the “best” drugs help somewhat with vertebral fractures (but the improvements are not durable). They really don’t help much with hip fractures and actually can weaken bones and precipitate those weird femur fractures.

So perhaps we need to follow a multi-pronged approach.

(1) weight bearing exercise, and perhaps augmented by using a vertical linear vibration platform. Not a powerplate, which is not vertical. I use mine for 10 minutes most days. Since I am not a heavy person, I feel that the bonus of the vertical vibration is especially important for me to get the necessary stimulation.

(2)Take vitamins D, Magnesium, K2 MK7 and also MK4. Get enough calcium but not too much. Read the “COMB” (Combination of Micro Nutrients) study. It focuses on these and also on Strontium Citrate. I won’t elaborate on Strontium here but you may want to read about it. I took Strontium for a while but stopped.

(3) Reduce inflammation and aim for an overall alkaline balance

(4) Estradiol if it is right for you (age, gender, menopausal status) or a SERM such as raloxifene

(5)Muscle strength, mobility and balance. This might be most important! I work on this a little nearly every day. Of course – avoid falls, avoid being bedridden or even just being sedentary.

My T-score (negative 3.7 at the hip) is terrible. But remember that the DXA measures mineral content of the bones. It does not assess the strength or brittleness of the lattice so its utility as a proxy of bone strength and flexibility is limited.

I had a consultation with Keith McDonald, hoping to hear of something new. No dice. But there is a very good series of talks by Dr. John Bilezikian (on Youtube) – these are lectures to his students on osteoporosis, and he reviews the drugs. He mentions the newest one, Evinity, which seems like one of those with some potentially nasty sides, so I have eschewed that one… Worth checking out the lectures though for a good overview.

Would love to hear if anyone has any other thoughts on strategies …

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#43

I feel like aspirin is only on the list because it causes “micro-bleeding” which leads to a reduction in blood iron, ferretin levels. It is much easier to just donate blood a few times a year.

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#44

More reason for SGLT2 inhibitors to be #1

From Healthspan:

SGLT2 Inhibitors as Metabolic Senolytics: Clearing Senescent Cells to Combat Pathological Aging

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Senolytic Therapy: What are you doing?
#45

Check with your doctor to see if you have any contraindications to low dose hydrochlorothiazide (12.5 mg/QD) as there are several RCTs in the literature suggesting it decreases calcium excretion and preserves bone mass. Bonus is that it is very low cost.

#46

Are you saying a person can have low bone density but high enough bone quality to offset some of the issues caused by low bone density? Perhaps low bone density is normally associated with poor bone quality, so “bone density” is a good-enough metric for most people but others or with certain interventions the quality can be good despite low density? I never considered this before.

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#47

But remember that the DXA measures mineral content of the bones. It does not assess the strength or brittleness of the lattice so its utility as a proxy of bone strength and flexibility is limited.

The DXA I get from UCSD includes a Trabecular Bone Score for the spine, which is a report on precisely that lattice. In my case, although I have a spinal bone density T-score of -2.7, TBS T-score for same is -0.7 (and actually +1.0 age matched). Report follows.

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#48

That is the claim made for CR in animals, the BMD is lower, but the architecture of the bone is superior, and as a result the net bone quality is superior - so the opposite of the drugs which increase BMD, but impair bone architecture leading to a net inferior quality of bone. I myself am unsure about the validity of this claim, particularly in humans on CR who can have lower BMD, perhaps to osteoporotic levels - I don’t know of any definitive evidence that their bone quality is superior; it might be possible, perhaps with compensatory bone supporting nutrition and/or exercise intervention, but I would not bet my health on that, rather I think osteoporosis and weaker bones might be a risk factor for CR in humans.

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#49

I would add GLP1-RA if glucose not in control with SGLT2i. After all the primary indication of GLP1-RA is diabetes. Obesity came later.

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#50

Yes my understanding is that the strength and flexibility of the lattice is an independent factor that can somewhat offset bone mineral density insufficiency. That is why just taking calcium to make sure the spaces in the lattice are filled up will not necessarily protect you if your lattice is brittle and you fall. That is why weight bearing exercise is so important – the little stresses (hormesis?) stimulates repair/rebuilding similarly to what happens with muscle.

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#51

As you note Krister, zero of the compounds in the OP list will halt or reverse aging. Maybe we will get a median or p90 extension of a decade or two if we are lucky from their combination, mostly coming from rapamycin.

Thus, in my opinion, to focus on them in research would be incorrect, unless it is to generate understanding in service of the larger goal of dramatically altering, halting or reversing aging.

Focusing on them is a good idea for practitioners who want to apply what we have now, though.

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#52

Makes sense to me.

My personal annoyance with the concept of “life extension”, i.e. living beyond 120 in a healthy manner is tied to elastin. Among all the puzzles that need to be solved elastin is so far down the list it boggles my mind.

We cannot live without it and after puberty we do not make any more of it and there is no known way to make any more. This limits human life span to max 120 years.

While I do appreciate the significant efforts in eliminating disease and other things that impair the quality of my health span and will take full advantage of anything I can afford, I have become highly skeptical of the “life extension” research crew that don’t seem to comprehend this simple fact.

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#54

Have you noticed any effects on resting heart rate and HRV suppression with GLP-1 use? I know it’s a known side effect, but I’m not sure if many people are actively tracking it. On low-dose semaglutide (0.25-0.5mg), I’ve experienced a higher RHR and significantly lower HRV, which is concerning since higher HRV is linked to better longevity. Curious if others have experienced the same.

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#55

I think one would need to weight the pros and cons.

My HRV is good due to my tVNS stimulating program. I’m not terribly concerned about RHR, mine is typically 60bpm.

I measure both every morning shortly after I wake and before getting out of bed. Have been doing that for over 4 years so I have good data on that.

Pros of GLP1-R’s, for me personally, far outweigh the cons of 2 markers that don’t affect my blood test results.

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#56

Interesting because I have read that small, low weight indivduals -
which you are more likely to be if you are calorie restricting - are at greater risk. Having more weight puts more force on the bones, which stimulates remodeling.