24 replies to this topic

[niner]

Skulachev's group published a paper last year that looks at the effects of mitochondrially targeted antioxidants on the lifespan of rodents. Their compounds are structurally similar to the adduct formed from C60 reacting with the fatty acids in olive oil, and all the effects of c60-oo are consistent with it being a mitochondrially targeted antioxidant. Skulachev's group has seen evidence that the enhancement of lifespan caused by their compounds are only seen when started early in life:

The unusual biphasic shape of the survival curves of mole-voles (Figure7) should be discussed in more detail. We suggest that the reason for this is that some animals received SkQ1 at a younger age than others. This seemed to be quite likely since among the mole-voles caught in the Siberian taiga were animals of various ages. As previously shown in our group [3, 4], one week-long SkQ1 treatment prolonged the lifespan of Drosophila if the treatment was carried out during the first week of life, but it was ineffective when given for the same period in the middle of life. Assuming SkQ1 is an inhibitor of the execution of the aging program, we speculate that it fails to induce a strong increase in lifespan of mice since the SkQ1-treated animals die, after all, as a result of cancer. If cancer is a very rare reason for death of mole-voles, a large increase in the lifespan by SkQ1 becomes possible. This possibility was confirmed when post mortem estimation of age of dead mole-voles was carried out. All the SkQ1-treated animals who died during first two years in captivity started to receive the antioxidant since the 2nd year of the life (Figures 7C,D).

The theoretical underpinning of this effect was eloquently described by Reason on his blog, Fight Aging. It is definitely worth a read.

A particular consequence of this effect might show up in AgeVivo's mouse experiment. He started c60-oo treatment on three middle-aged mice, one of which recently died from a tumor.

There are a number of reasons to believe that mitochondrial antioxidants will provide health benefits even if started late in life; see for example this post, not to mention the numerous reports we've had from people here.

[Andey]

Skulachev's group published a paper last year that looks at the effects of mitochondrially targeted antioxidants on the lifespan of rodents. Their compounds are structurally similar to the adduct formed from C60 reacting with the fatty acids in olive oil, and all the effects of c60-oo are consistent with it being a mitochondrially targeted antioxidant. Skulachev's group has seen evidence that the enhancement of lifespan caused by their compounds are only seen when started early in life:

The unusual biphasic shape of the survival curves of mole-voles (Figure7) should be discussed in more detail. We suggest that the reason for this is that some animals received SkQ1 at a younger age than others. This seemed to be quite likely since among the mole-voles caught in the Siberian taiga were animals of various ages. As previously shown in our group [3, 4], one week-long SkQ1 treatment prolonged the lifespan of Drosophila if the treatment was carried out during the first week of life, but it was ineffective when given for the same period in the middle of life. Assuming SkQ1 is an inhibitor of the execution of the aging program, we speculate that it fails to induce a strong increase in lifespan of mice since the SkQ1-treated animals die, after all, as a result of cancer. If cancer is a very rare reason for death of mole-voles, a large increase in the lifespan by SkQ1 becomes possible. This possibility was confirmed when post mortem estimation of age of dead mole-voles was carried out. All the SkQ1-treated animals who died during first two years in captivity started to receive the antioxidant since the 2nd year of the life (Figures 7C,D).

The theoretical underpinning of this effect was eloquently described by Reason on his blog, Fight Aging. It is definitely worth a read.

A particular consequence of this effect might show up in AgeVivo's mouse experiment. He started c60-oo treatment on three middle-aged mice, one of which recently died from a tumor.

There are a number of reasons to believe that mitochondrial antioxidants will provide health benefits even if started late in life; see for example this post, not to mention the numerous reports we've had from people here.

As I remember Baati experiment also starts with mid aged rats. Am I right ? (obviously it depends on what we call young and mid-aged and how this correlates with human lifespan)

Also it can be attributed to mice/rats phisiology itself. I found this info familiar and remember when I saw like this before.
In another experiment taking place now in Russia - big lifespan screening on mice started by Skulachev's sponsor - Alexander Chikunov (what a coincidence)) they screen about 1k substances on total 200k mice. And they also experience such effect on their most promising substance - when they started to give it to aged mice group they didnt got any benefit of it.

Edited by Andey, 03 November 2012 - 06:18 PM.

[zorba990]

The theoretical underpinning of this effect was eloquently described by Reason on his blog, Fight Aging. It is definitely worth a read.

Hmm. From that link:

• The signal to break down a mitochondrion is triggered by sufficient damage to its membrane: a sign that it's old, leaky, inefficient and needs to be replaced with a shiny new power plant.
• BUT: if a mitochondrion has had its DNA damaged to the point of stopping OXPHOS, it will no longer be producing free radicals that can damage its membrane. So it will never get broken down by a lysosome. When the time comes to divide and replicate, it will replicate its damaged DNA into new mitochondria. None of those new mitochondria will be producing free radicals via OXPHOS, and so will not be recycled either.
• One DNA-damaged, non-OXPHOS mitochondrion will eventually take over the entire mitochondrial population of a cell in this way. At that point, the trouble really gets started

So what kind of natural cocktail can we come up with that will start causing the non OXPHOS producing mitochondria to die off, or repairing the mitochondrial DNA?

http://newsroom.ucla...air-230241.aspx

Is it possible that the nOpm have weaker membranes than healthy ones and could succumb to a sort of chemotherapeutic approach like high dose fish oil, fasting, or ?

Some good pictures:
http://intelegen.com...restoration.htm

Autophagy:
http://www.ncbi.nlm....pubmed/18433711

Edited by zorba990, 03 November 2012 - 07:48 PM.

[maxwatt]

To answer the above post, there was a theory that resveratrol induced apoptosis in such defective mitochondria, as well as keeping healthy mitochondria from breaking down to produce excessive ROS. The muscle tissue of Auwerx' resveratrol fed rodents was replete with big, fat, healthy mitochondria whem compared to controls, who had far fewer, and smaller, mitochondria. The resveratrol-fed rodents remained physically active into old age, unlike the controls, but they did not live any longer.

If I am going to live to be 92, I want to be self-powered and not wheelchair-bound or tottering like most 92 year-olds seem to be. IF resveratrol is not the answer, I hope we come up with a good cocktail before too long.

[Anthony_Loera]

I think i had given an estimate here (in the comments) :

http://c60.net/were-to-get-pure-c60/


Basically the C60oo study had the mice start treatment at M10 (month 10) and treated them for 7 months, then the researchers stop the treatment.

That is like treating a human at 22 (with a lifespan estimate of 82.7 years) and treating them for 16 years. The treatment (if it would work on humans) would have the human live to over 152+ years, instead of 82.7 years.

Cheers
A

Edited by Anthony_Loera, 03 November 2012 - 11:06 PM.

[AgeVivo]

Bump. I'll try to read the theory described above of why c60oo would work when started in middle age but not well later and much better earlier (at the moment I have no such a priori). If someone can resume it in one or two sentences, that could be nice.

What I learned in labs is that too much theory in biology is wrong (does "if a then b" and "if b then c" imply "if a then c"? not so often. it needs to be very clear implications rather than the result of experiments with very particular conditions) but it seems you found here several things pointing to the same direction, plus it seems to be a theory for a large part of what aging is => to read in detail at the very least by curiosity

Edited by AgeVivo, 04 November 2012 - 04:15 AM.

[Mind]

I think AgeVivo means "summarize" it in one or two sentences.

One thing to remember is that C60oo is NOT currently theorized to promote rejuvenation, only to slow aging, which relates to what Maxwatt posted.

Does everyone want to be as healthy as possible when they reach 92? Of course. However, the ultimate goal is rejuvenation. If C60oo slows aging more than any other substance we know, that is great, and it would be a good treatment for a lot of the world's aging population. They might then be able to reach "longevity escape velocity". But sometimes I think, and many people (like Reason) would agree, there is way to much focus on slowing aging and not enough on rejuvenation. I think (from my layman's perspective) that the slowing aging mindset is affecting a lot of thought on lifestyle choices. CR, resveratrol, metformin, maybe C60, other possible CR-memetics, get all the discussion and headlines. Anything that promotes growth or rejuvenation is seen a "bad" in comparison. We are getting very knowledgeable about substances that slow metabolism, or slow the rate of damage, which is fine, but it is not productive in the long run. Substances and treatments that produce rejuvenation and growth are going to necessarily (from my basic understanding) work on different metabolic pathways that are most times antogonistic to the CR-memetic pathways.

You can use all of these substances and practice CR, and remain healthier than the average person, but you are still going to deteriorate and die in the end.

Edited by Mind, 04 November 2012 - 01:51 PM.

[niner]

To answer the above post, there was a theory that resveratrol induced apoptosis in such defective mitochondria, as well as keeping healthy mitochondria from breaking down to produce excessive ROS. The muscle tissue of Auwerx' resveratrol fed rodents was replete with big, fat, healthy mitochondria whem compared to controls, who had far fewer, and smaller, mitochondria. The resveratrol-fed rodents remained physically active into old age, unlike the controls, but they did not live any longer.

I wonder how that squares with this, taken from zorba's second link (source)

Mitochondria of healthy young adults respond differently to increased requirements for energy than older folks. Mitochondria of youthful people adapt to increased energy requirements by replicating rapidly. This results in more mitochondria producing more ATP for energy. However, as we age, our mitochondria replicate less readily. That means there are fewer mitochondria to produce the energy (Fig. 7). These fewer mitochondria attempt to respond to increased demand by hypertrophying (increasing in size) (Fig. 8). Unfortunately these larger mitochondria are less efficient and produce more damaging free radicals than their more youthful, more numerous, and smaller progenitors.

I hope we come up with a good cocktail before too long.

Mojitos have too much sugar. The search goes on...

[niner]

But sometimes I think, and many people (like Reason) would agree, there is way to much focus on slowing aging and not enough on rejuvenation. I think (from my layman's perspective) that the slowing aging mindset is affecting a lot of thought on lifestyle choices. CR, resveratrol, metformin, maybe C60, other possible CR-memetics, get all the discussion and headlines. Anything that promotes growth or rejuvenation is seen a "bad" in comparison.

Things that promote growth or rejuvenation aren't seen as "bad", they just don't get most people excited because they are inevitably inaccessible to average humans. They are usually laboratory curiosities that haven't been demonstrated in humans. In a recent post from Reason, he was puzzling over the fact that Americans are now said to be spending more on medicines (not to mention cosmetics) to control the effects of aging than any other category, yet there seems to be no interest at all in funding research into real rejuvenation. I posted a response there that I hope Reason will carefully consider. I'll reproduce it here in its entirety, since I think it needs wider dissemination in the hard core life extension community.

I think this can be explained pretty simply. People believe that they can postpone the appearance of aging, because it obviously works. Everyone knows that hair dye and boner pills and anti-TNF mabs work, and the message is getting out that wildly overpriced anti-wrinkle serums are somewhat effective as well. On the other hand, no one believes that anything can be done about real aging, because they haven't seen it. Demonstrate it, and they will come. I would advise that we put some research dollars into therapies that slow aging, rather than obsessing over our ultimate goal of therapies that reverse aging. We will be able to demonstrate the slowing of aging years, if not decades before we can demonstrate reversal. Proving that we can slow aging significantly will turn on a huge flow of money that can then be directed toward reversal.

I think c60 is the best thing that has ever come along for slowing aging, and while it may not be the sort of rejuvenative therapy that we're ultimately interested in, some of us who were not perfectly healthy have seen improvements that sure feel like rejuvenation.

[Turnbuckle]

One thing to remember is that C60oo is NOT currently theorized to promote rejuvenation, only to slow aging, which relates to what Maxwatt posted.

By whom is it not theorized? I think it does and I've seen evidence for it. So that's one.

[Mind]

One thing to remember is that C60oo is NOT currently theorized to promote rejuvenation, only to slow aging, which relates to what Maxwatt posted.

By whom is it not theorized? I think it does and I've seen evidence for it. So that's one.

I got that from reading all of the opinions bandied about in our Longecity C60 threads.

[maxwatt]

Human growth hormone (HGH) is claimed to promote rejuvenation, as is testosterone for men (and estrogens for women?). HGH is also said to promote cancer, and in excessive amounts enlargement of the internal organs resulting in a pot belly is a side effect. CR lowers HGH levels.

The doctor who gave me some shots I needed for travel practices bio-identical hormone therapy, and offered to email me papers to the effect that HGH is not cancer-promoting at lower doses, and I am curious. Low doses of these things have been used by (cheating) athletes to boost performance without short term negative effects, other than baldness from testosterone for some (those with DHT receptors in the scalp, a genetic trait that would eventually lead to baldness anyway.)

But yes, there are some doctors who do claim they can offer rejuvenation, and they charge for it. Those who have taken HGH have reported they love the effects. But physical rejuvenation is not necessarily life extending, it may shorten it.

If anyone is interested in this subject, PM me and I will start a thread on bio-identical hormone replacement, with whatever info I can glean from my source.

[Mind]

I gather from the likes of A4M, LEF, and some other rejuvenation-focused doctors that there are many thousands of people (probably tens of thousands) world-wide who are getting bio-identical hormone therapy. We should have some pretty good data on health/rejuvenation/life extension aspects of these therapies by now, right? Or is this the type of thing that is not going to be published in any journals? (sorry to derail the topic Niner, maybe can be split later)

Edited by Mind, 04 November 2012 - 04:05 PM.

[AgeVivo]

Again I'll read. Mind, at some time I've worked in labs with so-called rejuvenating hormones. Answer is: not at all, or very epsilon perhaps; pass your way. I fully agree that regeneration by improved use of stem cells is the biggest leap we currently foresee. I've followed a few of your news-selection on the topic and I was very impressed by your choices (any garage activity other than gardening? )

Edited by AgeVivo, 04 November 2012 - 04:53 PM.

[pleb]

Again off topic, my apologies, before finding the Longecity site i spent quite a lot of time reading about HGH, primarily after reading probably the same study study mentioned by Maxwatt, which was i believe published in the New England journal of medicine,

15 older males between the ages of 61 and 80 were given 1iu a day of HGH, at the end of 6 months it was reported that their cells were now the equivalent of 19 to 20 year olds and that they had also a loss of approximately 14 + percent body fat and an 8 percent increase in muscle mass, and reports of the following benefits,
some of the following is part of the study,


Human growth hormone (HGH) has been called a miracle anti-aging drug -- it's widely used in alternative clinics for the elderly as a means of rejuvenation. Human growth hormone is an effective anti-ageing drug due to its ability to return an adult's hormone levels to those of their youth.


Numerous studies have been conducted on the effects and benefits of HGH injections; the most complete study was done by Dr. Rudman and was published in the New England Journal of Medicine on July 5, 1990. The journal reported that men who had taken HGH injections had shown an 8.8 percent gain in lean muscle mass and a 14 percent decrease in body fat - without any change in diet or activity!
If you look at all the studies that have been conducted on injection therapy you will find the following list of facts demonstrating the benefits of HGH:
14% average decrease in fat
8.8% average increase in muscle and lean body structures
Improved skin texture resulting in a more youthful appearance
Fewer skin wrinkles
Increased bone density, reversal of osteoporosis
Faster healing of any type of injury, fracture, or wound
Greatly enhanced immunity and resistance to infection
Enhanced brain function, retention of intellect with aging
Improvement in Alzheimer and Parkinson's syndromes
Improved sex drive
Improvement in overall physical and mental well being
Improved exercise tolerance
Improved mood, with less depression and fatigue
Improved heart and kidney function
Greater cardiac output

HGH does extend life slightly but as it also causes the liver to produce IGF-1 which shortens life slightly (possibly this being a balance,) IGF-1 is what builds new muscle and is at the moment the only thing that can do that,
the recommended amount for rejuvenation is between 1iu to 2 iu a day,
and i have been unable to find one report of this amount causing any health problems and certainly none saying that it can cause or even effect the start or progress of cancer,

body builders are not taking small amounts i have this first hand from some of my sons friends most are taking anything between 4 and 10 iu a day, mostly the cheap Chinese generic HGH which can be bought for less than 1/20th of the cost of that produced in the west, and many are now starting to use IGF-1 as this is what builds muscle and is cheaper than HGH and Long3 IGF-1 which is three times as potent,

side effects are progressive and at the larger amounts used by BB’s start mostly with carpel tunnel syndrome which can also occure at small doses about 2 iu and upwards, but no reports of acromegaly even at the larger amounts, except in the subjects mentioned,
and the reports of large amounts causing acromegaly are also skewed as those with these side effects and most of the other problems which have caused it to be banned in the US except on prescription already had high levels of HGH secreted by their own pituary gland, but that stopping taking HGH resulted in the symptoms disappearing, after stopping the HGH injections,

[nowayout]

Since we don't even know if it will extend lifespan if started in early life, no amount of blah blah blah will change the fact that your question is really unanswerable right now by modern science.

[Junk Master]

Hey, rare to read such an informed account of HGH usage/effects Pleb! On thing I'd add is most users report an improvement in eyesight, which is why it's so popular with baseball players (and I suspect golfers, given Tiger Woods visits to a Canadian doctor specializing in "platelet rich plasma injections" that also happened to contain "growth factors" including HGH.

I suspect, intermittent use of HGH would most certainly improve quality of life for those over 45, but I would be concerned with excessive use, and with HGH potentially accelerating insulin resistance.

CR with a break every six months for six months of paleo, HIT training, and HGH?

[pleb]

Hi JM thanks, the eyesight improvements and insulin resistance are new info ill look into that so thanks again as i also have a sight problem which it may help,
i'm moving to Mex in about 3 months, i had intended starting it now but can't find a reliable supplier for the small amount
i would use (1 kit 100iu ) ,
Genscience the largest Chinese manufacturer makes Jintropin but after a run in with the FDA won't send to the US and will only sell a minimum of 5 kits and i don't really fancy going through Mex customs with vials of white powder,!!!

and as you say quite a few oldies take it intermittently to cut down on cost,

[Anthony_Loera]

Hi pleb,

you wont have a problem with white powder in vials. Just tag them as personal use medicine.
Most ex-pats take lots of medicine this way into Mex.

Cheers
A

[pleb]

Hi Anthony thanks i'll look into that,

you mention tagged for personal use, is that an official tag with a docs signature or just a stick on label signed by me, ?

Cheers,

John

[Mind]

For those of use that are getting older and more frail, whose mortality risk is getting uncomfortably high with each passing year, it seems there could an optimal balance to be struck between pro-growth and age-slowing diet/lifestyle methods (as Junk Master kind-of suggested).

Minimal hormone therapy to keep hormone levels a little closer to post-puberty optimums..... coupled with known health promoting methods like CR, exercise, perhaps C60oo, a diet rich in foods/supps that hit the CR-memetic/anti-cancer metabolic pathways.

But really, this is just speculation because data on hormone therapy is a bit sparse, IMO, because of the negative bias that exists in mainstream media and the obnoxious zero-tolerance PED policies of professional sports leagues. Private sports leagues are free to ban PEDs, of course, but unfortunately their attitude of "natural performance and nothing else" permeates the culture and holds back progress.

[Anthony_Loera]

Hi Anthony thanks i'll look into that,

you mention tagged for personal use, is that an official tag with a docs signature or just a stick on label signed by me, ?

Cheers,

John

Typically its a stick on label by you. If you have a docs paperwork that is ok, but they never (at least in my experience) ask for it.

I usually have told them its medicine, and they let it go by if they see you are not from Mexico.

Now coming into the usa is another matter... You will need a docs prescription (even if its a mex doc) to come in, if you are stopped for a search. Again, it doesn't happen often, but US customs will require it if they do manually go through your bags and look at unlabeled meds.

Cheers
A

Edited by Anthony_Loera, 06 November 2012 - 06:51 PM.

[pleb]

Thanks Anthony, the last time i went in they didn't ask about my meds, but with over 4 kits of JIN still unused that would be 40+vials at 10iu each I'm sure that will show up on the scanner and raise questions as that would be over a years supply at 1 iu a day,
i think I'll forgo getting it now and order once I'm there,

Cheers

John

[jroseland]

Does this still stand?

One thing to remember is that C60oo is NOT currently theorized to promote rejuvenation, only to slow aging

 

[sensei]

I think i had given an estimate here (in the comments) :

http://c60.net/were-to-get-pure-c60/


Basically the C60oo study had the mice start treatment at M10 (month 10) and treated them for 7 months, then the researchers stop the treatment.

That is like treating a human at 22 (with a lifespan estimate of 82.7 years) and treating them for 16 years. The treatment (if it would work on humans) would have the human live to over 152+ years, instead of 82.7 years.

Cheers
A

 

ANthony -- you are way off

 

a 10 month rat is aquivalent to a 35-45 year oild human