Cell Repair
Telomeres and Teleomere Length
In order to have any discussion of cell repair I must first introduce telomeres and explain why they are so important. Telomeres are special protein structures of DNA sequenced at the end of the DNA that creates a cap on the ends of the linear chromosomes. Every time a cell divides it loses telomers in the process. When a cell's telomeres gets as small as 4-6 kbs in length it can trigger a non-replicating cell known as senescence or cell death known as apoptis. You'll hear this called the 'end-replication problem. Telomeres prevent senescence if DNA is broken and prevents DNA from end-joining with other broken DNA strands. They provide a mechanism for counting cell divisions and protect chromosome end stability which if not in place could turn to cancer. There is a second type of DNA damage that you might here people discussing. This is called ROS (reactive oxygen species). Mitochondrial DNA (mtDNA) when damaged can create ROS which also can play a major role in cell death by creating additional stress on telomeres which are already suffering repair.
In order to have any discussion of cell repair I must first introduce telomeres and explain why they are so important. Telomeres are special protein structures of DNA sequenced at the end of the DNA that creates a cap on the ends of the linear chromosomes. Every time a cell divides it loses telomers in the process. When a cell's telomeres gets as small as 4-6 kbs in length it can trigger a non-replicating cell known as senescence or cell death known as apoptis. You'll hear this called the 'end-replication problem. Telomeres prevent senescence if DNA is broken and prevents DNA from end-joining with other broken DNA strands. They provide a mechanism for counting cell divisions and protect chromosome end stability which if not in place could turn to cancer. There is a second type of DNA damage that you might here people discussing. This is called ROS (reactive oxygen species). Mitochondrial DNA (mtDNA) when damaged can create ROS which also can play a major role in cell death by creating additional stress on telomeres which are already suffering repair.
Picture courtesy of Nature Magazine pg 342, 17 February 2011
So, as you can see it is important that I protect the telomeres in my body since they eliminate age related disease by senescence, also aging and in a perfect world prevent cancer. By introducing a enzyme called Telomerase I can encourage the cell to create its own telomere's thus preventing telomere shortening and senescence by cell replication. Telomarase seems to work independently of creating telomeres and creates against oxidative stress thus defeating ROS. Studies suggest there is a synergism between mitochondria and telomere damage within cells. Reducing telomere shortening will reduce aging yet it is important to note that there are other things that can cause cell death and unless I can prevent these hazards then immortality is a proverbial red herring. At best I can only prevent the effects of aging and perhaps extend human life with this knowledge.
It has been demonstrated in numerous studies that activating telomerase in mice can reverse the affects of aging by senescence. In some tests, even if by a little genetic slight of hand, mice have even grown younger with telomerase activation. Other studies demonstrate that telomere therapy does not cause cancer. The suggestion that telomerace activation could cause cancer gives this big rat a feeling for caution since this science is so new. I am not writing a thesis here so you should do your own research. I am placing some relevant studies in the Links section of this site. I am merely providing a backdrop for my thinking and actions in taking telomerase activators and inhibitors.
Astragalus
Jim Green's website attracted my attention a couple of years ago when I found his postings and musings concerning longevity. He had been testing telomerase activators and is very knowledgeable about the science of home remedies and commercial remedies. He also has a series of photos which shows he has achieved some level of success. His photos aren't the best and the website for me was difficult to read and navigate. If it were not for his wealth of knowledge I probably would have discounted this highly organized site!
This except describes what he refers to as "Telomere Remodeling with Cyclic Telomerase Activation"
"... Run telomerase activation as a square wave with a cycle period of a month, using 2 weeks of telomerase activation followed by 2 weeks of anticancer telomerase inhibition. Avoiding high polyphenol foods during the first 2 weeks helps separate telomerase activation phase from the telomerase inhibition phase to implement a push-pull telomere elongation engine approach to life extension propulsion. Now we can catch a ride on a monthly telomerase activation cycle and attempt to ride it into eternity like a new pet hitched to the moon for a perpetual lifetime."
One thing is sure and that's that astragalus Root powder and astragalus extract are both his telomerase activator of choice. He has studied many of the commercial applications and it is his opinion that the root and it's extract are actually more potent.
"However, these medicines don't work as well at contemporary dosages for increasing average telomere length as astragalus root powder at 33 grams/day or 1/3 as much astragalus Root extract, though it is certainly more convenient to wolf down just one pill. - June 14, 2012"
If it's good enough for Jim (He takes 33mg of Root per day) it is good enough for me. There is a second consideration for me and that is cost. The commercial products are of a magnitude more expensive. I pay $8.00 a pound for astragalus Root. This is enough for me to make it through one two week phase of my regimen.
I'll show you Jim's two week cycle. From what I can tell he prefers the astragalus extract.
"(1) Two weeks using telomerase activation with astragalus root powder ( < 33 grams/day), or astragalus root extract (< 11 grams/day), astragalosides, other telomerase activators, with TRF1 t-loop closure protein stripping via tankyrase 1 phosphorylation with insulin expressed via Fenugreek and/or Gymnema Sylvestre to open telomere t-loops for access by the telomerase holoenzyme. Simultaneously we downregulate P16INK4a (which can make recovery from senescence irrecoverable) with Id-1 helix-loop-helix transcription factor obtainable by stimultion with nerve growth factor obtained from acetyl-L-carnitine, PQQ, huperzine A, carnosic acid, rosemary extract, or other nerve growth factor boosters. I may also use colostrum skin cream or a slurry of colostrum in water on my skin for transdermal whole-body application of colostrum, which contains growth factors that lengthen dermal fibroblast telomeres, in addition to TGF-beta that reconstructs collagen and elastin in the extracellular matrix. (I might precede this long-range telomere-lengthening treatment featuring colostrum with hyaluronic acid in water or "hyaluronic acid serum" applied to the skin as a temporary wrinkle remover.) In addition, I may rub astragalus root extract into my scalp and gums. Black cohosh, perhaps the most inexpensive telomerase activator, may also be used. Black cohosh causes no estrogenic side effects in exercising males at 4 caps/day in standard formulations. Exercise promotes 12 different endogenous telomerase activators such as HGH that may be further boosted by supplements such as alpha-GPC and arginine.
(2) Then we go two weeks using telomerase inhibitors [81s/TI] not used during the first two weeks.
This procedure is expected to produce telomere elongations of less than 38 base pairs per month, that is, less than 456 base pairs/year. I note that RevGenetics now recommends a two-week cycle for telomerase activation, alternating a telomerase activator like Astral Fruit C (cycloastragenol) or Astral Fruit (astragaloside IV) one week with life-extending telomerease inhibitors including resveratrol, quercetin and other supplements the next week.
About 50-200 telomere base pairs are typically lost per cell division, although antioxidants may reduce the loss rate. Humans have about 50 cell divisions available from the embryonic stage of development, so this procedure may outdistance the aging process, although treatment should continue for years. TA Sciences did as well as the maximum here in blood granulocytes, 230 base pairs during each 3-month telomerase-on pulse in the Patton protocol using TA-41, which was an astragalus extract. This corresponds to a rejuvenation rate of about 9 years backwards in time per year, or 0.75 years/month."
You can see that he doesn't really suggest an inhibitor here. I have to dig further into his writings to determine what he suggests.
"Telomerase inhibitors garlic, turmeric (curcumin), resveratrol, quercetin, vitamin E, green tea, melatonin, silymarin, fish oil EPA, cocoa, cacao bean products, chocolate, and dietary polyphenols may be taken during the 2nd two weeks, but must not be taken during the first two weeks. Retinoic acid, a telomerase inhibitor that also inhibits the expression of P16INK4A (which makes replicative senescence irreversible) can also be used during the telomerase inhibition phase. Retinoic acid inhibits P16INK4A expression in oral keratinocytes."
Resveratrol and Milk Thistle Seed
Most of these are easy to get into my diet. I have chosen resveratrol as it has many age defying benefits alone. My second choice is silymarin. I will get this from powdered milk thistle seed which I can buy for $6.00 lb. Milk Thistle has so many health benefits I just couldn't pass this one up. This will also last me for the second half of the cycle since I will be taking it in roughly the same amounts as the astragalus. These two will be my major inhibitors yet if you look at my regime you might notice there are other supplements that I throwing in the mix. Most of these are nootropics or have some other health function I enjoy.
It took me a while to figure out how to dose the astragalus and the powdered milk thistle seed. If I'm going for a strict 33 grams then I will need about 2 1/4 tbs which comes to approximately 32 gms. I decided that I didn't like trying to measure half a tablespoon and chose to go with 2 tsps three times a day which comes to exactly 30 gms. 1 tsp equals 5 grams. It dawned on me that Jim is a bigger man than myself so I would likely get similar effects if I take a little less than he.
Polyphenols
One thing I need to be concerned with is this statement, "Avoiding high polyphenol foods during the first 2 weeks helps separate telomerase activation phase from the telomerase inhibition phase to implement a push-pull telomere elongation engine approach to life extension propulsion. " In short I need to stay away from nuts, fruits and vegetables during the first two weeks. These contain the bulk of polyphenol. Great, another low-carb diet. Not exactly, I can drink milk... and lots of it. If I eat anything with polyphenols, milk will neutralize it!
Standardization
How do I prepare my herbs for ingestion? I simply heat my water in the microwave till it's good and hot. I then spoon two tsps of astragalus or milk thistle seed powder into the cup and stir. I let it steep for about 10 minutes. I drink the whole cup and stir it between sips to keep the powder suspended in the water. I do this three times a day to get to my 30 grams. I may want to boil the powdered milk thistle seed to get it to release the most silymarin. For bio-availability I drink the whole thing anyhow and don't feel that boiling it for long periods of time will make much of a difference.
Astragaloside IV is the component found in astragalus that is responsible for telomere growth. This extract is crazy expensive. I found the following in the Longecity forums and thought it was interesting enough to post here.
9 grams of Astragalus = 14.4mg of Astragaloside IV
15 grams of Astragalus = 24mg of Astragaloside IV
30 grams of Astragalus = 48mg of Astragaloside IV
60 grams of Astragalus = 96mg of Astragaloside IV
120 grams of Astragalus = 192mg of Astragaloside IV
Astragaloside IV comes in 50mg capsules and the daily recommended dosage is 1 to 2 per day. I am currently on just 30 grams of astragalus a day which would be about 1 dosage of Astragloside IV. I may bump this up to 60 grams a day in the future. It is prudent to be cautious and to take things slowly.
Carnosine
Carnosine is an amino acid peptide found in all proteins. It is particularly found in meats. While it's mechanisms of effect are not quite known, it is commonly excepted that Canosine is a vital and useful component in the prevention of cell death (AKA Old Age). It has been proven to prevent the hardening and accumulation of junk between cells (AGEs) and it delays and reverses cell death (senescence). We do know that something good is going on inside the cells when taking carnosine. It is suspected that it works by protecting telomeres from shortening. It is neither and activator or an inhibitor but it is a telomere protector. People taking this supplement boast visible anecdotal results.
So, as you can see it is important that I protect the telomeres in my body since they eliminate age related disease by senescence, also aging and in a perfect world prevent cancer. By introducing a enzyme called Telomerase I can encourage the cell to create its own telomere's thus preventing telomere shortening and senescence by cell replication. Telomarase seems to work independently of creating telomeres and creates against oxidative stress thus defeating ROS. Studies suggest there is a synergism between mitochondria and telomere damage within cells. Reducing telomere shortening will reduce aging yet it is important to note that there are other things that can cause cell death and unless I can prevent these hazards then immortality is a proverbial red herring. At best I can only prevent the effects of aging and perhaps extend human life with this knowledge.
It has been demonstrated in numerous studies that activating telomerase in mice can reverse the affects of aging by senescence. In some tests, even if by a little genetic slight of hand, mice have even grown younger with telomerase activation. Other studies demonstrate that telomere therapy does not cause cancer. The suggestion that telomerace activation could cause cancer gives this big rat a feeling for caution since this science is so new. I am not writing a thesis here so you should do your own research. I am placing some relevant studies in the Links section of this site. I am merely providing a backdrop for my thinking and actions in taking telomerase activators and inhibitors.
Astragalus
Jim Green's website attracted my attention a couple of years ago when I found his postings and musings concerning longevity. He had been testing telomerase activators and is very knowledgeable about the science of home remedies and commercial remedies. He also has a series of photos which shows he has achieved some level of success. His photos aren't the best and the website for me was difficult to read and navigate. If it were not for his wealth of knowledge I probably would have discounted this highly organized site!
This except describes what he refers to as "Telomere Remodeling with Cyclic Telomerase Activation"
"... Run telomerase activation as a square wave with a cycle period of a month, using 2 weeks of telomerase activation followed by 2 weeks of anticancer telomerase inhibition. Avoiding high polyphenol foods during the first 2 weeks helps separate telomerase activation phase from the telomerase inhibition phase to implement a push-pull telomere elongation engine approach to life extension propulsion. Now we can catch a ride on a monthly telomerase activation cycle and attempt to ride it into eternity like a new pet hitched to the moon for a perpetual lifetime."
One thing is sure and that's that astragalus Root powder and astragalus extract are both his telomerase activator of choice. He has studied many of the commercial applications and it is his opinion that the root and it's extract are actually more potent.
"However, these medicines don't work as well at contemporary dosages for increasing average telomere length as astragalus root powder at 33 grams/day or 1/3 as much astragalus Root extract, though it is certainly more convenient to wolf down just one pill. - June 14, 2012"
If it's good enough for Jim (He takes 33mg of Root per day) it is good enough for me. There is a second consideration for me and that is cost. The commercial products are of a magnitude more expensive. I pay $8.00 a pound for astragalus Root. This is enough for me to make it through one two week phase of my regimen.
I'll show you Jim's two week cycle. From what I can tell he prefers the astragalus extract.
"(1) Two weeks using telomerase activation with astragalus root powder ( < 33 grams/day), or astragalus root extract (< 11 grams/day), astragalosides, other telomerase activators, with TRF1 t-loop closure protein stripping via tankyrase 1 phosphorylation with insulin expressed via Fenugreek and/or Gymnema Sylvestre to open telomere t-loops for access by the telomerase holoenzyme. Simultaneously we downregulate P16INK4a (which can make recovery from senescence irrecoverable) with Id-1 helix-loop-helix transcription factor obtainable by stimultion with nerve growth factor obtained from acetyl-L-carnitine, PQQ, huperzine A, carnosic acid, rosemary extract, or other nerve growth factor boosters. I may also use colostrum skin cream or a slurry of colostrum in water on my skin for transdermal whole-body application of colostrum, which contains growth factors that lengthen dermal fibroblast telomeres, in addition to TGF-beta that reconstructs collagen and elastin in the extracellular matrix. (I might precede this long-range telomere-lengthening treatment featuring colostrum with hyaluronic acid in water or "hyaluronic acid serum" applied to the skin as a temporary wrinkle remover.) In addition, I may rub astragalus root extract into my scalp and gums. Black cohosh, perhaps the most inexpensive telomerase activator, may also be used. Black cohosh causes no estrogenic side effects in exercising males at 4 caps/day in standard formulations. Exercise promotes 12 different endogenous telomerase activators such as HGH that may be further boosted by supplements such as alpha-GPC and arginine.
(2) Then we go two weeks using telomerase inhibitors [81s/TI] not used during the first two weeks.
This procedure is expected to produce telomere elongations of less than 38 base pairs per month, that is, less than 456 base pairs/year. I note that RevGenetics now recommends a two-week cycle for telomerase activation, alternating a telomerase activator like Astral Fruit C (cycloastragenol) or Astral Fruit (astragaloside IV) one week with life-extending telomerease inhibitors including resveratrol, quercetin and other supplements the next week.
About 50-200 telomere base pairs are typically lost per cell division, although antioxidants may reduce the loss rate. Humans have about 50 cell divisions available from the embryonic stage of development, so this procedure may outdistance the aging process, although treatment should continue for years. TA Sciences did as well as the maximum here in blood granulocytes, 230 base pairs during each 3-month telomerase-on pulse in the Patton protocol using TA-41, which was an astragalus extract. This corresponds to a rejuvenation rate of about 9 years backwards in time per year, or 0.75 years/month."
You can see that he doesn't really suggest an inhibitor here. I have to dig further into his writings to determine what he suggests.
"Telomerase inhibitors garlic, turmeric (curcumin), resveratrol, quercetin, vitamin E, green tea, melatonin, silymarin, fish oil EPA, cocoa, cacao bean products, chocolate, and dietary polyphenols may be taken during the 2nd two weeks, but must not be taken during the first two weeks. Retinoic acid, a telomerase inhibitor that also inhibits the expression of P16INK4A (which makes replicative senescence irreversible) can also be used during the telomerase inhibition phase. Retinoic acid inhibits P16INK4A expression in oral keratinocytes."
Resveratrol and Milk Thistle Seed
Most of these are easy to get into my diet. I have chosen resveratrol as it has many age defying benefits alone. My second choice is silymarin. I will get this from powdered milk thistle seed which I can buy for $6.00 lb. Milk Thistle has so many health benefits I just couldn't pass this one up. This will also last me for the second half of the cycle since I will be taking it in roughly the same amounts as the astragalus. These two will be my major inhibitors yet if you look at my regime you might notice there are other supplements that I throwing in the mix. Most of these are nootropics or have some other health function I enjoy.
It took me a while to figure out how to dose the astragalus and the powdered milk thistle seed. If I'm going for a strict 33 grams then I will need about 2 1/4 tbs which comes to approximately 32 gms. I decided that I didn't like trying to measure half a tablespoon and chose to go with 2 tsps three times a day which comes to exactly 30 gms. 1 tsp equals 5 grams. It dawned on me that Jim is a bigger man than myself so I would likely get similar effects if I take a little less than he.
Polyphenols
One thing I need to be concerned with is this statement, "Avoiding high polyphenol foods during the first 2 weeks helps separate telomerase activation phase from the telomerase inhibition phase to implement a push-pull telomere elongation engine approach to life extension propulsion. " In short I need to stay away from nuts, fruits and vegetables during the first two weeks. These contain the bulk of polyphenol. Great, another low-carb diet. Not exactly, I can drink milk... and lots of it. If I eat anything with polyphenols, milk will neutralize it!
Standardization
How do I prepare my herbs for ingestion? I simply heat my water in the microwave till it's good and hot. I then spoon two tsps of astragalus or milk thistle seed powder into the cup and stir. I let it steep for about 10 minutes. I drink the whole cup and stir it between sips to keep the powder suspended in the water. I do this three times a day to get to my 30 grams. I may want to boil the powdered milk thistle seed to get it to release the most silymarin. For bio-availability I drink the whole thing anyhow and don't feel that boiling it for long periods of time will make much of a difference.
Astragaloside IV is the component found in astragalus that is responsible for telomere growth. This extract is crazy expensive. I found the following in the Longecity forums and thought it was interesting enough to post here.
9 grams of Astragalus = 14.4mg of Astragaloside IV
15 grams of Astragalus = 24mg of Astragaloside IV
30 grams of Astragalus = 48mg of Astragaloside IV
60 grams of Astragalus = 96mg of Astragaloside IV
120 grams of Astragalus = 192mg of Astragaloside IV
Astragaloside IV comes in 50mg capsules and the daily recommended dosage is 1 to 2 per day. I am currently on just 30 grams of astragalus a day which would be about 1 dosage of Astragloside IV. I may bump this up to 60 grams a day in the future. It is prudent to be cautious and to take things slowly.
Carnosine
Carnosine is an amino acid peptide found in all proteins. It is particularly found in meats. While it's mechanisms of effect are not quite known, it is commonly excepted that Canosine is a vital and useful component in the prevention of cell death (AKA Old Age). It has been proven to prevent the hardening and accumulation of junk between cells (AGEs) and it delays and reverses cell death (senescence). We do know that something good is going on inside the cells when taking carnosine. It is suspected that it works by protecting telomeres from shortening. It is neither and activator or an inhibitor but it is a telomere protector. People taking this supplement boast visible anecdotal results.