Reversal of Aging by Biological Intervention

Recent progress in understanding the biological nature of aging and recent progress in biomedical technology means that it may soon be possible to reverse aging. Imahamster has followed this field as an interested lay person for many years. Aubrey D. N. J. de Grey is a researcher in this area whose ideas Imahamster finds very interesting. Seems appropriate to begin this thread with a link to an article by Aubrey de Grey.

http://research.mednet.ucla.edu/pmts/sens/article.htm

 

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Imahamster thanks Shaman for contributing the following links.

(Removed links that continued to fail.)

Gene Therapy in the CNS:
http://www.chgb.org.cn/special/therapy/pdf/cns.pdf

Premature Aging in Children:
http://www.sciam.com/askexpert/medicine/medicine13.html

 

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Stem cells for eggs and sperm also control aging in roundworm

http://www.eurekalert.org/pub_releases/2002-01/uoc--scf011502.php

 

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Gene Inserted in Male Germ-Line Cells Creates Transgenic Mice

http://www.techreview.com/offthewire/3001_1.asp

 

Hi hamster,

Not all your links seem to be functional. But your main link in the opening post is fine. Hey great stuff.

I have to admit I started following such research some 18 years ago. There has been a lot of progress and a few breakthroughs, but nothing that has really caught the attention of the public.

Your main link outlines this pessimism quite well. Most people seem to think that anti-aging or age reversal will never happen and that outlook also prevents appropriate investment and funding. I wish I knew how to change that outlook. It would certainly help to have a more convincing breakthrough that the typical lay person could relate to.

It is also an enormous pity that stem cell research is going to be so severely restricted while we have to wait for politicians and religionists to overcome their squeamishness.

But what gives me such great hope is the increasing number of Discovery channel and TV science documentaries that do cover some of the research in this area. That to me indicates a build up of activity that is reaching the general public. If politicians and religion do not artificially block it then we should see progress increase at a geometric rate consistent with related fields in science and technology.

Keep posting your links.

Cris

 

Chris, this hamster enjoys sharing such seeds.

Some of the links are to universities. This hamster has had trouble accessing university sites before. They often limit outside access. The links have worked for me at least once. (Couldn’t get through tonight.)

This hamster does not believe this technology can be stopped. The promise is too great. The potential demand is too powerful. The main limiting factor is lack of public awareness. Even that may be good as the public might demand applications before the basic science is ready.

Exciting times.

 

Exciting? Most definitely. This is a great time to be alive. But I'm 49 so I need solutions fairly soon.

 

Promising, indeed...

~~~

Mucho thanks, Hamster... (and Shaman)

Enjoyed your recent posts. Glad to see this topic circulating again. Keep the links coming as sharing such seeds is just another way to increase that much desired 'public awareness.' Might even scare up a real discussion around here if you aren't careful.

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~~~

And Cris:

I share your hope even as I offer you fair warning: Wouldn't surprise me at all to see Imahamster bringing in more tasty bits. (extraordinary harvesting skills, this one) You might want to empty a mental pouch just in case.

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~~~

Speaking of hope, I hope to catch up on some good reading here this weekend.

Looking forward,

Counterbalance

 

Personally I think reversing aging is not going to be too easy (may be impossible). I think prevention is a better goal for the time being until the aging process is better understood.

It's interesting that in many ways germ cells are immortal as they propagate through generations, but the large number of late periods/early natural abortions etc, make me think that it is just a fraction of undamaged cells that survive.

You can improve damage repair all you want, but stability of biological systems over very long periods of time isn't likely to be all that easy (nonlinearity can be good and bad). Taking a system that has de-stabilized and trying to get it back on track is even harder.

 

Kmguru, Imahamster is no expert but is willing to take a first pass on answering your questions.

“Does anyone know if the DNA remains exactly the same (ie. the entire sequence) between childhood and old age?”

DNA suffers damage from many causes. Most damage is repaired by enzymes. Some types of damage are not repaired and in some cases the repair process itself fails. Some forms of cancer may be linked to DNA damage.

DNA expression is modified by such changes as added methyl groups. The cellular environment also affects gene expression and protein synthesis. Hormonal and structural signals from other cells also affect gene expression. The total system may accumulate errors.

Ongoing studies are using “gene” chips that simultaneously analyze the activity of thousands of genes to compare old tissue to young tissue. The gene expression profiles are significantly different and may lead to discovery of critical “age” genes.

“Are there cells in the body that are perfect duplicates time after time?”

As Scilosopher mentioned germ cells are nearly immortal. These cells seem to have extra protection against DNA damage (or better repair mechanisms).

“Does hamster know what part telomerase enzyme plays, since the inhibitor is now available for cancer treatments? “

The role of telomerase is not simple. Cultured cells typically die out as the Hayflick limit is reached. Each division results in the chromosome telomeres shortening. When the telomeres get too short gene expression is impaired. Some scientists see this as a natural protection against cancer. A wildly dividing cell line eventually dies off. By adding telomerase to the cell culture the Hayflick limit can be exceeded as the telomeres are restored. Many but not all cancers produce telomerase.

Due to the cloning technique used to produce Dolly she had shortened telomeres. Other cloning techniques have produced animals with telomeres longer than normal for that species. Cloning several generations of mice with shorter and shorter telomeres showed no observable change until the 5th (?) generation. Later generations rapidly deteriorated. There seemed to be no correlation between telomere length and animal life span until the telomere was significantly shortened.

Mice have been created with the telomerase gene turned off and others with an extra telomerase gene. Didn’t seem to affect lifespan. (As this hamster recalls?)

Telomerase is active in the germ cells and in some stem cells.

All the above seem to indicate that telomerase plays no role in aging. Well it’s not that simple. Injury or chronic inflammation may cause excessive cell turn over. In that case telomere shortening could lead to cell abnormalities that may contribute to aging traits. In this hamster’s opinion telomeres play a secondary aging role.

“Does adding RNA as a nutrition supplement help in cell damage repair?”

This hamster knows of people who take RNA for that purpose. This hamster is not aware of evidence suggesting it helps. (Nor of evidence to the contrary.)

There are many compounds being tested as antioxidants. To be effective the antioxidant must reach the site the free radicals are being produced.

There are other compounds being tested that break cross linkages formed by glycation. Again the compounds must reach the site to be effective.

(This hamster welcomes corrections and clarification of the above. This is complicated stuff and this hamster could use help.)

 

Cancer seems to be entirely the result of DNA damage. There are specific mutations like p53 and others that are present in 90+% of specific types of cancer. Families with increased tendency towards cancer tend to already have one copy of one of the genes mutated. I can't remember the specific details right now (I'm suffering from one hell of a hang over. Why do people ever buy me drinks? I know when to stop buying them, just not when to turn them down.), but it's interesting to note that most cancers actually have a whole family of mutations. Telomerase is often activated, apoptosis regulators (like p53), are almost always inactivated, DNA damage repair genes are often broken. It isn't clear though if the high number of multiple mutations in cancers happens to cause the cancer or mainly as a result of the cancer essentailly evolving to be more cancerous as it goes (the genomes in the various cells in a cancer vary noticeably). If they cause the cancer though, we might accumulate more mutations than we think over the course of our lives.

Telomeres have two main functions - to keep the ends of chromosomes from being recognized as a double strand breaks and being "repaired" (which leads to chromosome fusion), and to deal with the fact that a RNA primer is required for DNA replication such that you would lose 5 bases each round of replication if there wasn't some way to account for such. Telomerase itself has an RNA template that it can use to add repeats to the end of the chromosomes, which means that there is no iformation being lost and it can just add more repeats after replication. The pathway involving telomerase is linked into apoptotic pathways. Apoptosis is programmed cell death that is used to remove misbehaving cells (interesting analogy to hari-kari [sp?]).

I actually thought the 5 generations in mice was a telomerase knockout (or maybe it's both). If I'm remembering correctly, mice have much longer telomeres than humans and don't seem to use them as a cell life control mechanism in the same way we do. I don't think the lifespan of the mice was affected until they were sickly in the 5th generation. That was more likely due to the fusion and bridging of chromosomes as this can cause duplication and loss of DNA which has a strong phenotypic effect. There were also telomerase knock outs done in arabadopsis and no phenotype was noticed for 6 generations and the line survived for about 10 generations. It is interesting to note that the plants with a telomerase knockout actually lived LONGER than normal. Lots of hand waving ensued. Who knows what it means. In general though telomerase is related to cellular aging more than organismal aging.

I've never heard of people taking RNA as a supplement. Not having seen the research, I would tend to say it's a gimmick and doesn't work. Our body is suffused with RNAses which digest RNA, presumably to protect against retroviruses (their genome is encoded with RNA not DNA). Maybe the bases themselves are useful though as the enzymes just chops them up to that level so maybe they can then be put to good use ...

 

Scilospher, thank you.

Kmguru, as you showed interest in supplements this hamster will chatter. (Hehe, it's Kmguru's fault.)

The presumed beneficial affects of virtually all supplements are based on folk medicine, animal studies, and “theory”.

By folk medicine this hamster means lore that has been passed down that certain substances have beneficial affect. This hamster includes traditional Chinese herbal medicine that has evolved over thousands of years. Western medicine has tended to ignore such remedies.

There are several reasons why Chinese herbal medicine has not been incorporated into Western medical practice. First, the Chinese model of body, mind, and health does not match the Western model. (Doesn’t mean one is right and the other is wrong. It’s an uncomfortable mix.) Second, safety and efficacy tests for drugs are extremely expensive, too expensive for a natural substance that cannot be patented. Third, herbs are an extremely complicated mix of active substances. The potency of these substances varies widely due to individual plant differences and processing. Many of these herbs are quite powerful and given that the potency may vary ten-fold or more may be dangerous. (Especially for people who believe that since they are “natural” and require no prescription then they are harmless.) By comparison note that on average Western drugs are only effective on only two thirds of their target population. Complications resulting from Western drugs are common and often serious.

Many claims are based on animal studies. This is only natural as testing in humans is expensive, long, and in some cases unethical. However there are problems with these claims.

The first problem is an advertising practice tantamount to fraud. There are thousands and thousands of animal studies. Often one study “shows” one thing while another seems to show the opposite. Supplement pushers may quote one or two studies showing benefit while ignoring many more that showed no benefit (and in a few cases even harm).

The second problem is that it’s difficult to extrapolate animal studies to humans, especially when making claims of a longer, healthier life. A researcher may have chosen a particular laboratory mouse strain because it is short-lived. (Researchers have careers and cannot wait extra years to complete an experiment.) There are many reasons why such a mouse strain might have a longer average or even maximum lifespan when supplemented that imply little to nothing about benefits to humans.

Finally, there is “theory”. Someone develops a theory of aging. Someone else further theorizes that if that aging theory is correct then a certain intervention should be effective. Based on very shaky reasoning a third person then suggests taking a supplement.

This situation is changing. Due to the popularity of herbal medicines Western scientists have begun to study them. E.g., statistical population studies correlating reported tea usage against disease history have indicated that green and black tea may help prevent certain cancers.

This hamster has taken mega-doses of vitamins and minerals for years. (Mostly on the principle that it’s unlikely to hurt and may help.) This hamster has taken growth hormone releasers in the past. (They may or may not do anything. Might even vary for each person.) Recent evidence indicates higher growth hormone levels may decrease life span. (Basically the story is too complicated to draw any conclusions.)

This hamster believes that in the relatively near future there will be effective drugs. That is, drugs that significantly reduce wrinkles or hair loss by improving the biological function of the tissue. When they become available a person won’t be able to avoid hearing about them. (The commercials touting the “breakthroughs” will become very annoying.)

A little further off there will be drugs and treatments that are effective against less cosmetic traits of aging.

Then someone will announce that they have reversed aging in a mouse.

 

Kmguru, Imahamster enjoyed your post and am using it as an excuse to chatter on hormones. Don’t really disagree with you but do wish to take the discussion a level deeper. Also wish to state up front that this us merely a hamster’s view of a subject full of controversy. (The known complexity is levels beyond this hamster’s understanding.)

“2. Older people who have taken human growth hormone have found their body reversing the aging process.”

This statement might be misleading. This hamster knows of one small study of older people whose GH levels were very low for their age. GH injections produced favorable changes in muscle mass, skin, and mood. (These are good changes but it may be overstating to say that GH reversed aging.) These changes disappeared when the GH injections were discontinued. Follow up studies weren’t nearly so clear. (But received far less publicity than the initial report. Go figure.) This hamster believes the subjects in the original study were deficient in GH so GH helped them. (This hamster would appreciate links to recent studies of GH supplementation.)

GH can increase cell division. This may lead to premature aging or cancer. Knocking out a GH gene produced a dwarf line of mice that significantly outlived the normal mice. Adding an extra GH gene produced a giant mouse with shortened lifespan.

The story is further complicated because animals change significantly as they age. Supplementing with GH while relatively young might shorten life span. But if GH increases elderly muscle mass it may extend elderly life span. Active tissue such as muscle provides a reservoir helping elderly people stave off disease. (Likewise strength training helps elderly people.)

The increased danger of cancer might be avoided if the increased cell division could be stopped. That might be possible by interfering with the cell division process. Green tea seems to do that.

This stuff is complicated. Much is unknown.

One simple theory is that restoring hormones to their “youth” levels will restore youth. The body is far more complicated than that. Based on this theory many people take DHEA. There have now been many studies on DHEA. DHEA doesn’t reverse aging, doesn’t build muscles, doesn’t aid fat loss. DHEA does seem to have some minor benefits.

Clearly some post-menopausal women benefit from hormone therapy. This hamster suspects that many men past fifty might also benefit from hormone therapy. Does this have much to do with aging? This hamster doesn’t know. (Imahamster fully supports improved quality of life.)

Is there a plant compound that could be absorbed through the skin and improve DNA or cell repair?

One can hope. If there is this hamster suspects it will be found by the companies willing to spend the money to search for it. Such a company would then modify the compound to reduce toxicity and increase efficacy. The company would develop delivery systems so that the drug got to all the places where the drug was needed. The company would then spend $200,000,000 proving the drug was safe and effective. If the company is lucky they have a winner. THEN the company will charge an arm and leg and customers will happily lineup to buy it.

Other companies will copy the first company’s success. Might even produce a better drug. Prices will come down. If a true anti-aging drug is discovered the government might intervene and mandate inexpensive supplies for every citizen.

Imahamster strongly agrees that we need to find out what works and what doesn’t. A quick assay that could show whether a compound might have anti-aging properties would greatly speed the search for new compounds.

 

Kmguru, glad it’s helping your dog. Interesting that your treatment may have helped a liver problem. This hamster knows of only two dangers associated with DHEA. The first is that it is an important hormone. Significantly elevating DHEA levels could be dangerous. This hamster feels modest dosages are safe and has taken DHEA and will likely take DHEA in the future. The second danger is common to any hormone. Most of the hormone is broken down in the liver which elevates liver enzyme levels which can aggravate liver problems. (Obviously not a problem for your dog as his levels tested normal.) DHEA can cause liver cancer in fish but the mechanism by which it did so does not seem to occur in humans or most other mammals. (Hope the exception was guinea pigs and not hamsters.)

The news group sci.life-extension is an excellent place to discuss life extension supplements. http://groups.google.com/groups?hl=en&safe=off&group=sci.life-extension

A quick search for “turmeric” brought up 42 references. Many of the posters are quite knowledgeable. Look forward to hearing the results from your skin test.

 

42 references, interesting number ...

Kmguru,
Typically from the biotech perspective gene therapy only refers to introducing a different copy of some gene into at least a subset of cells in your body. Mutation isn't directly involved, although the copy that is inserted may have been modified.

Is this the typical "new age" definition? I get very nervous when different people mean very different things when they use the same phrase. It is certainly possible for the type of compounds you mention to have therapuetic effects, but the terminology you use is not necessarily what I would.

 

Keep young and beautiful (Fruit flies only)

Drug extends maximal and average fruit fly life span.

http://www.eurekalert.org/pub_releases/2002-01/ns-kya012302.php