49 replies to this topic

[normalizing]

this is very very recent study i have found on sciencedaily; https://www.scienced...60315121054.htm and i managed to get the full copy of it at; http://www.impactjou...65&path[]=22203 and read through and found it very very interesting. out of so many compounds only 6 have life extending qualities and surprisingly its not some of those we would expect!

 

anyway im interested in comments about this, especially from niner since i know he enjoys this type of stuff a lot

[Ohm]

A list of stuff that human beings have been consuming in one shape or another for a long time.

 

"Willow bark was commonly used during the time of Hippocrates, when people were advised to chew on it to relieve pain and fever. The study showed that it increases the average and maximum chronological lifespan of yeast by 475 per cent and 369 per cent, respectively. This represents a much greater effect than rapamycin and metformin, the two best drugs known for their anti-aging effects."

 

We can safely conclude based on human history that willow bark does not have the same effect on human beings as it does on yeast.

 

Likewise, astragalus is probably not going to activate your telomerase and therefore extend your life.  Nor will it likely induce cancer.  Both outcomes are desired/feared lately but based on the fact that the Chinese have consumed astragalus for a long long time without incident of 150 year olds or cancer epidemics it is relatively safe to conclude that this plant will not do what we hope/think it will.

 

More simply, if human beings consuming a plant or animal had the effect of extending life in any meaningful way it would have already become known and likely brutally fought over a very very very long time ago...

[Castiel]

It depends on dosing.  If the required dose is within a minute range to be most effective, it might not have been tested.  Also consistency.   If people only took willow bark to treat some things from time to time, obviously that is not a consistent dose.

[Ohm]

It might depend on dosing.  It might not.  

 

It might depend on a handful of factors, various compounds being consumed in very specific amounts, perhaps ratios of calories being skewed a certain way, being cycled in various ways, so as to make the whole thing give new meaning to the words "highly improbable".  Then again, it might not.

 

What is likely to happen is that people, based on very limited information, will flock to the trough and gorge themselves with a "more is better" mentality not unlike EGCG leading to the exact opposite of what they are trying to prevent in the first place (detriment to their health, specifically in this case liver damage) at worst, or simply throwing their money away at best.

[Castiel]

 

It might depend on dosing.  It might not.

 

 

Well dose makes the poison, or cure.   And consistency is also important.

 

But unless people in the past had reason to consistently consume this at a dose that is not too high or too low, we can't dismiss its potential... further tests are needed.

[Darryl]

In yeast.  While the usual experimental progression (yeast, roundworm, fly, rodent, monkey) makes sense for cost reasons, so many promising compounds that extend yeast, roundworm, or fly longevity have no effect in mammals that I wouldn't get excited (yet)

 

The promising extracts:

 

Black cohosh root: Native American medicinal with serotonin & GABA_A receptor agonist activity & phytosterols

Valerian root: GABA_A receptor agonist and adenosine A1 receptor antagonist/inverse agonist

Purple passionflower plant: GABA_A receptor agonist and high flavonoid & alkaloid content

Gingko biloba leaf: possibly helpful in dementia. Wiki not helpful with active compounds, and tonight I'm lazy.

Celery seed: high in apigenin and luteolin, effective hormetics 

Willow bark: salicylates are known AMPK inducers.

 

For the most part, we're looking at common polyphenol effects. The GABA_A receptor agonist activity of three of these extracts is intriguing. They didn't test lavender (whose aromatic compound linalool is one of the best known GABA_A receptor agonists). Do yeast even have GABA receptors? It's not clear, but they certainly have analogs to GABA receptor associated protein that are important in autophagy, and many longevity interventions are dependent on autophagy upregulation. Might be worth looking into.

[normalizing]

nothing about resveratrol... i guess it became too overrated and studies are aimed at new things

Edited by normalizing, 16 March 2016 - 03:24 AM.

[niner]

Their extract "PE7" was from Japanese Knotweed root, so that should have had ~40-50% resveratrol, along with various other things.  This is an interesting paper from the point of view of the molecular biology involved.  However, as Darryl pointed out, it's in yeast, and those results don't usually translate into mammals very well.

[joelcairo]

When you say "only 6" compounds were identified (out of 37), that minimized the implications of the study. From the original paper: "Each of the six longevity-extending PEs [plant extracts] increases lifespan more efficiently than any lifespan-prolonging chemical compound currently known." It's only yeast, but nonetheless a remarkable result if confirmed.

 

...Also, thinking about it, it's not clear to me that some of the remaining compounds didn't extend lifespan as well, just not to such a remarkable degree. I didn't read the entire study in detail, but they seemed to only publish the data for the candidates that passed their screen, so it's hard to tell.

[normalizing]

i sure hope they move on to rats next and try the same extracts see the differences

[normalizing]

so how does willow bark compare better to simply taking aspirin?

[Castiel]

 

i sure hope they move on to rats next and try the same extracts see the differences

 

Rats or mice would be nice.  But another quick study that could be done is gene expression tests on human cells exposed to the extracts.

 

After resveratrol was tested on yeast, tests on human cells showed it tripled survival to radiation exposure, also iirc it induced expression changes similar to calorie restriction but not complete, only partial changes.

 

In any case, if there was no error in procedure, this nearly quadrupled lifespan.  Usually you see under 65% extension even with Calorie Restriction in most organisms, greater increases often require genetic engineering.  If anyone recalls similar from other compounds on simple organisms' maximum lifespan,  it would be interesting to know and see what resulted of them in higher organisms.

[joelcairo]

Speaking of calorie restriction, an interesting result was that

 

1. Growing the yeast under CR conditions extended lifespan -- not surprisingly.

 

2. Each of the 6 plant extracts identified extended lifespan much more than CR did.

 

3. When the plant extracts were used under CR conditions, the increase in lifespan was clearly much less in every case than with the plant extract alone.

 

Not sure what this means. Of course it only applies to these specific experimental conditions, but maybe CR isn't the gold standard after all.

[normalizing]

i didnt see this. so doing CR and taking those extracts seem like a bad idea wow. so its like how resveratrol might mimic CR in obese individuals but i dunno of studies done on it being used under CR conditions, it might lower life expectations. which means CR should be practiced careful and you shouldnt be taking any supplements under this practice because of some unknown reason. perhaps the body is already in a state of stress and doesnt require excessive hormesis, right?

[joelcairo]

Just speculating, my interpretation would be that CR has a myriad of effects and some of them are negative. Given that we need food to live, I guess that would not be so surprising. Maybe these plant extracts can achieve the beneficial results (e.g. AMPK activation) without inducing the harmful effects of starvation.

[Tom Andre F. (ex shinobi)]

almost anything increase yeast lifespan.. For me its like increase hair growth (and look for the rt pcr expression of the related growth factors, wnt..) on mice .. Any herbs increase hair growth on mice.

 

What we want is : increase lifespan on mamals versus control and versus CR. And to date, the only one I found doing so is beta-lapachone. I would like someone else showing me im wrong..

 

and please dont mention the studies where they directly modified the genes or induced a retro virus, I speak about mice fed studies

Edited by Tom Andre F. (ex shinobi), 18 March 2016 - 12:30 AM.

[niner]

Here's a database of lifespan studies:  http://lifespandb.sageweb.org/

 

There are a number of compounds that increase lifespan in mammals.  (e.g. rapamycin)  It's pretty easy to fool yourself, however, if there are defects in animal husbandry that are killing your control group while the compound provides some type of protection against whatever is wrong with the husbandry.  Michael has posted on this a lot.

 

The best work seems to be done under the NIA's ITP.  There's a list of published paper that might be useful.

[Tom Andre F. (ex shinobi)]

thank you niner, the DB is very impressive and useful especially due to the summary allowed.

 

As I see, there is very few molecules tested (if we remove growth hormone for instance). As for rapamycin, i have to look deeper but since its an immunosuppressor, i wouldnt feel confident into this. Sometimes you can increase lifespan as you said in mamals prone to develop cancer just by feeding anti cancer drug. The useful studies are very few unfortunately. Again I add that to my favorite in order to look deeper

[normalizing]

i still dont understand how rapamycin works. isnt it the opposite that should increase lifespan, immunomodulatory, instead of immunosuppresion? if thats the case, lots of immunosupressors out there that might be safer

[Tom Andre F. (ex shinobi)]

There is a difference between immunomodulatory and immunosuppression, I mean they are not opposite. Most often your body start to attack itself, its a part of aging. Thats why we can target short term living or especially mice designed to have particularly such deaseased i imagin.. A natural safer immunosupressor (more acurately : reducer) is vit D

[Polyamine]

If you want to extend life, all you have to do is lower the intracellular loss of the polyamines and decrease pathogenic DNA from being incorporated into our DNA.  Sounds easy doesn't it......

[Tom Andre F. (ex shinobi)]

spermidine supplementation ?

[normalizing]

spermidine is readily available in most food i dont see it being really vital

[Skyguy2005]

I swear by Ginkgo Biloba!

[treonsverdery]

this is a copy n paste list from the paper

PE4 Cimicifuga racemosa Root and rhizome

PE5 Valeriana officinalis L. Root
 

PE6 Passiflora incarnate L.Whole plant

PE8 Ginkgo biloba Leaf

PE12 Apium graveolens L. Seed
    

PE21
    

Salix alba
    

Bark
    

Idunn Technologies

Edited by treonsverdery, 13 August 2016 - 12:22 AM.

[Castiel]

A comment on past human usage of herbs and supplements with regards to potential life extension.   There are many factors that might seriously handicap survival in ancient populations even if most of the aging process was somehow significantly slowed or halted.  For example unless you stop cataract formation, that will impede ease of survival in ancient times.  If you don't stop tooth loss, that will also interfere with the chances of survival.   The region that controls automated breathing in humans as in many other animals is subject to neuron loss over time, the central nervous system cannot regenerate such damage, eventually the system will become probabilistic and there will be a high probability of breathing stopping over night without waking up to restart breathing and thus leading to death.

 

Any of these would probably result in likelihood of early death even where a substance that interferes with the aging process were used.  And as I've stated previously a standardized dose is a must, and also an optimal dose range.  Random variations of intake are not ideal, and can also take it to ineffective or toxic ranges.

 

Regards willow bark here's my post on the other related thread:

 

Well it might depend on the dose,  High dose chronic aspirin can supposedly lead to kidney injury and can also require vitamin k supplementation to avoid adversely affecting clotting ability.  So if it requires a high dose we'd need to find what the highest safe dose is, and if it requires pairing with another protective compound to be used at effective doses....

 

But the aging process is very fundamental, if something affects the aging process in multiple species it is highly promising, and should be tested on human cells, and higher animals.

 

 

 

[tunt01]

 

Gingko biloba leaf: possibly helpful in dementia. Wiki not helpful with active compounds, and tonight I'm lazy.

 

 

I think you want to start looking at EGb761.

 

 

 

Effects of ginkgo biloba extract EGb761 on expression of RAGE and LRP-1 in cerebral microvascular endothelial cells under chronic hypoxia and hypoglycemia.

Yan FL1, Zheng Y, Zhao FD.

 

Alzheimer's disease (AD), characterized by accumulation of amyloid-beta protein (Abeta) in brain parenchyma, is closely associated with brain ischemia. Decreased clearance of Abeta from brain is the main cause of Abeta accumulation in sporadic AD. However, the mechanisms underlying ischemia-mediated AD pathogenesis remain unclear. The receptor for advanced end glycation products (RAGE) and low-density lipoprotein receptor-related protein-1 (LRP-1) expressed at blood brain barrier (BBB) are actively involved in Abeta clearance. RAGE is thought to be a primary transporter of Abeta across BBB into the brain from the systemic circulation, while LRP-1 mediates the transport of Abeta out of the brain. Ginkgo biloba extract EGb761, a traditional Chinese medicine, has been widely used in the treatment of AD. To investigate the effects of EGb761 on the expression of RAGE and LRP-1 in endothelial cells in response to ischemic injury, we cultured bEnd.3 cells, an immortalized mouse cerebral microvessel endothelial cell line, under a chronic hypoxic and hypoglycemic condition (CHH) to mimic ischemic injury of BBB, and then treated with EGb 761. We found that EGb 761 markedly ameliorated the damage (evaluated by MTT assay) from CHH. Moreover, we demonstrated that CHH led to a significant increase in the expression of RAGE both at the mRNA and protein levels at all times (24, 36, and 48 h), conversely; CHH induced a dramatic decrease in LRP-1 mRNA and protein expression at both 36 and 48 h. The results indicated that CHH has differential effects on the expression of RAGE and LRP-1. Furthermore, EGb761 significantly reversed CHH-induced upregulation of RAGE expression and downregulation of LRP-1 expression. Our findings suggest that EGb761 favor clearance of Abeta via regulating the expression of RAGE and LRP-1 during brain ischemia. This may provide a new insight into a possible molecular mechanism underlying brain ischemia-mediated AD pathogenesis, and potential therapeutic application of EGb 761 in treatment of AD.

 

 

 

 

 

Amyloid precursor protein metabolism is regulated toward alpha-secretase pathway by Ginkgo biloba extracts.

Colciaghi F1, Borroni B, Zimmermann M, Bellone C, Longhi A, Padovani A, Cattabeni F, Christen Y, Di Luca M.

Author information

Abstract

Clinical trials report that Ginkgo biloba extracts (e.g., EGb761) reduce cognitive symptoms in age-associated memory impairment and dementia, including Alzheimer disease (AD). However, the mechanisms behind their neuroprotective ability remain to be fully established. In this study, the effect of EGb761 on the amyloid precursor protein (APP) metabolism has been investigated by both in vitro and in vivo models. To this aim, alpha-secretase, the enzyme regulating the non-amyloidogenic processing of APP and the release of alphaAPPs, the alpha-secretase metabolite, were studied in superfusates of hippocampal slices after EGb761 incubation, and in hippocampi and cortices of EGb761-treated rats. PKC translocation state was evaluated as well. EGb761 increases alphaAPPs release through a PKC-independent manner. This effect is not accompanied by a modification of either APP forms or alpha-secretase expression. Moreover, EGb761 influence on alphaAPPs release was strictly dependent on treatment dosage. Our findings suggest that the benefit of EGb761 reported by previous clinical studies is underscored by a specific biological mechanism of this compound on APP metabolism, directly affecting the release of the non-amyloidogenic metabolite. Additional research will be needed to clearly define the effective clinical relevance, thus considering EGb761 as a possible supplementary treatment in dementing diseases.

 

 

[limerence]

I don't really trust websites or publications with the word science in the name. Always odd conflict of interest

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[treonsverdery]

I just read that aspirin causes mice to live about 10-15% longer at the Jenage.de database.  That goes well with the paper of the topic, where yeast live asbout 11.4 days compared with about 2.4 for the controls.  Aspirin is a modified version of willow bark extract, salicyclic acid.  the Jenage.de databse is at http://lifespandb.sa...earch?q=Aspirin

[normalizing]

yeh but aspirin works much better than williow bark exactly because it is bettered modified version. try willow bark and compare if you dont believe