: Death, Aging, Rejuvenation (Part 1) by: Aleksandr Kavokin, MD,PhD I would like to raise a question: Is Rejuvenation possible and how to approach it? This is just my own opinion about possible procedures. I used certain

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Death, Aging, Rejuvenation (Part 1)

by: Aleksandr Kavokin, MD,PhD


I would like to raise a question: Is Rejuvenation possible and how to approach it? This is just my own opinion about possible procedures. I used certain techniques based on a theory. As strange as it sounds some of those techniques and procedures might actually worked.
There are several hundreds theories of aging. New and old ones. Different authors classify them differently.
I would divide all those theories into 2 groups :
1. Theories of Deterioration from external cause. "Wear and tear". Theory of free radicals damage is most fashionable at present time. Antioxidants are considered a cure. Benefits of caloric restriction are often explained by that theory. The theory has good objective support in scientific literature. Other theories of this group included changes of bacteria in the gut, radiation and accumulation of mutations during life of an individual, etc. - many more of those theories were discussed in the XX century. 2. Internal clock - theories.
I would divide the "internal clock" theories into 2 more subgroups: 1. Internal clock on the level of cell. Telomeres shortening is the most discussed in literature at present. 2. Internal clock on the level of organism. Growth hormone changes was a recent example of discussion.
Authors are usually very cautious and objective in scientific literature. Telomeres are usually discussed in connection with "immortal" cancer cells. Caloric restriction is discussed as a mean of longevity (not rejuvenation per se). Level of growth hormone (GH) or insulin-like growth factor drops in aged persons.
Mass media speculates wider: telomeres restoration - possible immortal life, growth hormone will rejuvenate you, etc.
Original scientific studies usually do not speculate about this. In no way for example drop of GH level in elderly means that just giving it back will make you young again.
Scientific literature rarely discuss "Rejuvenation" as it is. Authors mostly talk about "longevity". This is very different story. Longevity in a wheelchair is very distinct from a youth playing soccer. One proven method to reach longevity is caloric restriction. Often they say it is the only proven technique. Using antioxidants as a method to prolong life is in the same category. To put simple, the Theory says: nutrition produce products of oxidation - peroxides, etc. These products damage DNA, proteins, etc. Cell ages. Caloric restriction switches metabolic pathways. There are less free radicals. Hence longevity. Antioxidants work in similar way - they remove free radicals. Another speculation is that caloric restriction starting at young age delays reproductive age in animals and this slows down biological clocks and prolongs life until an environment with high nutrition supply is found. Animals look small and undeveloped.
Caloric restriction significantly (25%-100% and more) prolonged life in worms, flies, spiders, rats, mice, etc. Experiments on monkeys and humans are under way and will take decades.
Well, it is all good in experiments and theories. Some argue: why in this case prisoners of concentration camps do not live longer. Another example came from "Scientific American" - a person had caloric restriction of something 20 years or more - no effect - he just looks like very thin undernourished person of 50 years. Examples of opposite opinion also exist (tribes or groups with low food consumption or high antioxidants consumption have more centenarians than general population). Maybe you really need to start at 10 years of age, look malnourished and weak for the whole life and live to 100 years, getting to your puberty at 25. Antioxidants also bring many controversy. Vitamin E did not show many benefits though it was a big hope for prevention of many diseases of old age. And so on. Today there are big trials that disprove the theory. Tomorrow - great experiments that confirm the theory, at least partially. Many big trials and experiments are published in leading journals - Science, Nature, PNAS, New England JM, JAMA, etc.
One bias for caloric restriction experiment in my opinion is following. Rats live in cage 30cmX60cm for their whole life. There are at least five rats or 20 mice. They live couple years and die. During the experiments they are celebrities when they live 5 years - some lucky ones. The Food is a balanced mixture of nutrition. Caloric restriction is - 60% of their regular meal. They practically don't move - there is no space in cage. Mostly they sleep whole day. Sometime they fight and mate. They live in those conditions at Yale, at Med U of South Carolina, at Russian State Medical University and I think everywhere else. To compare our fellow humans we would place 10 people on area of 20 square metres (200 sq. feet) for 50 years in a row, feeding them with what they want but all the same - let say junk food from McDonalds.
I remember my cat (who was partially wild) stole meat and ate until it started to vomit. He repeated it many times when he was able to steal some steak or whatever. The same happens in wild - lions have maybe one successful hunt out of ten. When they catch a prey, they eat like crazy. Much more than they can digest at the moment. So it looks like there is an instinct. Eat as much as possible. This is not a joke - 60% of people in western countries are overweight. Abundant high calorie food and lack of activity. It does not seem that for these people any internal mechanism restricts food consumption. Applying this back to rats, we can see that what is considered normal consumption - "ad lib" - maybe actually big overfeeding of the animals in these cages. In this case 60% of caloric restriction would be just what rats need, just what the calories they spend in lazy, uneventful daily life. So called "control", "normal" rats - that fed as they usually fed might be compared for fat overweight humans. They consume junk food. They prone to the bunch of diseases of obesity and low activity. Heart diseases, strokes, variety of cancers, arthritis, etc. In this case all the hype about caloric restriction would just be brought to the business of mere balancing diet and activity in so called "calorie-restricted animals". I haven't seen any discussion of this problem. I might be wrong. This is why I use caloric restriction for myself. I did not work with worms and spiders. But my guess would be that they all are also in artificial standardized conditions. "Control" worms might be also overfed. To put rats into bigger cages (to increase activity in control group and balance calories and catabolism) would be incredibly expensive. Even at present conditions because of "animal lovers" and bunch of other regulations and considerations (e.g. sterile conditions), the price of animal housing is sky-high.
You would say animals in wild would live longer because they balance activity and consumption. Well, recently I read that life span of animals in wild is shorter than animals in captivity. Correct me if I am wrong: pandas live 15-20 years in nature and 20-30 in zoos, bears 20-25 in nature and 30-40 in captivity. Civilization has certain benefits - vaccinations, good medical care, more or less good hygiene. So just moving into wild conditions wouldn't make you younger or allow to live longer.
Now, to discuss rejuvenation procedures, I would need to talk about aging first. In this case Rejuvenation could be considered as reversal of aging (deterioration). Longevity is different story - it is prolonged life span. Rejuvenation supposedly should lead to longevity. But longevity is not equal to Rejuvenation. Aging leads to Death eventually. It is easier to discuss from that end.
All written here is just plain speculation, take it with a grain of salt.
- continued in Part 2

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