NAD+ OptimizersHigh dose of metformin with the SIRT1 activator reduces lifespan

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AlbertY
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High dose of metformin with the SIRT1 activator reduces lifespan

Post by AlbertY » Mon Jun 29, 2020 8:51 pm

It is known that severe CR is detrimental in very old age. And metformin can block the beneficial effects of exercise. Recent research suggests it might also be the case for a high dose of NMN. All of this evidence suggests that we shouldn't blindly combine longevity regimes, especially for older people.

Now this paper shows that combining a high dose of metformin with the SIRT1 activator, SRT1720, reduces lifespan in aged mice fed a high-fat diet.
SRT1720, a sirtuin1-activator, and metformin (MET), an antidiabetic drug, confer health and lifespan benefits when administered individually. It is unclear whether combination of the two compounds could lead to additional benefits. Groups of 56-week-old C57BL/6J male mice were fed a high-fat diet (HFD) alone or supplemented with either SRT1720 (2 g/kg food), a high dose of MET (1% w/w food), or a combination of both. Animals were monitored for survival, body weight, food consumption, body composition and rotarod performance. Mice treated with MET alone did not have improved longevity, and lifespan was dramatically reduced by combination of MET with SRT1720. Although all groups of animals were consuming similar amounts of food, mice on MET or MET+SRT1720 showed a sharp reduction in body weight. SRT1720+MET mice also had lower percent body fat combined with better performance on the rotarod compared to controls. These data suggest that co-treatment of SRT1720 with MET is detrimental to survival at the doses used and, therefore, risk-benefits of combining lifespan-extending drugs especially in older populations needs to be systematically evaluated.
https://academic.oup.com/biomedgerontol ... 48/5859153


Ph.D. student at Harvard Medical School, doing research on aging
Newage
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by Newage » Mon Jun 29, 2020 10:49 pm

Goes along with the “very old advice of everything in moderation”
What’s good for one is not necessarily good for another...We still all have a long way to go on this longevity journey.
ChrisBON
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by ChrisBON » Mon Jul 06, 2020 8:17 pm

AlbertY wrote:
Mon Jun 29, 2020 8:51 pm
It is known that severe CR is detrimental in very old age. And metformin can block the beneficial effects of exercise. Recent research suggests it might also be the case for a high dose of NMN. All of this evidence suggests that we shouldn't blindly combine longevity regimes, especially for older people.

Now this paper shows that combining a high dose of metformin with the SIRT1 activator, SRT1720, reduces lifespan in aged mice fed a high-fat diet.
SRT1720, a sirtuin1-activator, and metformin (MET), an antidiabetic drug, confer health and lifespan benefits when administered individually. It is unclear whether combination of the two compounds could lead to additional benefits. Groups of 56-week-old C57BL/6J male mice were fed a high-fat diet (HFD) alone or supplemented with either SRT1720 (2 g/kg food), a high dose of MET (1% w/w food), or a combination of both. Animals were monitored for survival, body weight, food consumption, body composition and rotarod performance. Mice treated with MET alone did not have improved longevity, and lifespan was dramatically reduced by combination of MET with SRT1720. Although all groups of animals were consuming similar amounts of food, mice on MET or MET+SRT1720 showed a sharp reduction in body weight. SRT1720+MET mice also had lower percent body fat combined with better performance on the rotarod compared to controls. These data suggest that co-treatment of SRT1720 with MET is detrimental to survival at the doses used and, therefore, risk-benefits of combining lifespan-extending drugs especially in older populations needs to be systematically evaluated.
https://academic.oup.com/biomedgerontol ... 48/5859153
I am assuming by CR you mean Calorie Restriction? I would agree.

I am also thinking with NMN with my elderly mother to keep it at 250mg per day max, and rather than taking Resveratrol, have her take Curcumin, because it is also a great anti-inflammatory.

I am thinking we may find that we need to use caution with the very young and the very old.

Mind you if I was 84 I would be testing all this to the limits. Pickleball is my hero!!!
Taking:
NMN since June, 2019 (started at 250mg, 500mg as of Oct 1st)
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Resveratrol since Sept 2019
Astaxanthin 10mg since October 20th
Blueberry concentrate 500 mg since October 20th
Berberine 250 mg since October 20th
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AlbertY
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by AlbertY » Tue Jul 07, 2020 2:29 pm

ChrisBON wrote:
Mon Jul 06, 2020 8:17 pm

I am assuming by CR you mean Calorie Restriction? I would agree.

I am also thinking with NMN with my elderly mother to keep it at 250mg per day max, and rather than taking Resveratrol, have her take Curcumin, because it is also a great anti-inflammatory.

I am thinking we may find that we need to use caution with the very young and the very old.

Mind you if I was 84 I would be testing all this to the limits. Pickleball is my hero!!!
Yes, CR is for calorie restriction (also now people also like to use DR -- dietary restriction, as it stands for restriction on both calorie and feeding time). Sorry if these acronyms are confusing.

And wise choice, curcumin is a very mild compound in my mind.
Ph.D. student at Harvard Medical School, doing research on aging
drkris69
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by drkris69 » Thu Jul 09, 2020 8:59 pm

So this paper is stating that taking NMN with Metformin is NOT beneficial for longevity? It seems to contradict what's out there from Dr. Sinclair. Hmm, need more evidence on which way to go.
Newage
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by Newage » Thu Jul 09, 2020 10:58 pm

drkris69 wrote:
Thu Jul 09, 2020 8:59 pm
So this paper is stating that taking NMN with Metformin is NOT beneficial for longevity? It seems to contradict what's out there from Dr. Sinclair. Hmm, need more evidence on which way to go.
Yes drkris69
Unfortunately the left hand is not always in sync with the right hand... :roll:
drkris69
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by drkris69 » Fri Jul 10, 2020 2:16 pm

The other question is that a high dose of metformin with SIRT1 is bad for "older people". Whats considered old? 50, 60 80?
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AlbertY
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Re: High dose of metformin with the SIRT1 activator reduces lifespan

Post by AlbertY » Sun Jul 12, 2020 2:25 pm

drkris69 wrote:
Thu Jul 09, 2020 8:59 pm
So this paper is stating that taking NMN with Metformin is NOT beneficial for longevity? It seems to contradict what's out there from Dr. Sinclair. Hmm, need more evidence on which way to go.
Not NMN, it's a SIRT1 activator, similar to resveratrol. And it's old rats with a high-fat diet, you can see it is a very artificial setting. So it is unclear how to apply the result to humans with a normal diet.
Ph.D. student at Harvard Medical School, doing research on aging
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