Abstract;
A remarkable paradigm shift is in how to get end-less life, to 6 independent paradigm, only one showing any progress!
1. 1. With demonstrable progress, Bottom-up DNA methods with limitless rejuvenation.
2. 2. Bio-evolution with periodic reversion to womb-state as in jelly fish.
3. 3. Download of Brain to silicon and commanded robot bodies.
4. 4. Permanent periodic refix of stem cells and immune system. Thymus regeneration.
5. With demonstrable progress, DNA methods with Yamanaka factors
6. With demonstrable progress, Top Down Stem cell E5 exosomes methods
My work has identified 4 genes that underlie the full digraph of Hallmarks of Aging. These are Sirt1, AMPk, mTOR, and igf-1. Of these, all but mTOR must be boosted for reducing/reversing aging. The mTOR is central to human comfort and technological evolution to improve human life through comfort. All, but mTOR, are boosted with diet restriction, mTOR reduces, all reducing aging. Best Aging is common in Indian Naturopathy – take the aged couple and subject them to extreme diet restrictions without mercy. After 3 months, food restriction is to normal levels, but most survivors eat less than even that. Humans are reduced to near skeletons anyway. Extreme food restriction kills any diabetes and boosts the genes. This method works but I recommend against it – very few survive to end.
All modern conveniences increase mTOR, hence reduce age! Hence the puzzle. Even better food increases mTOR. Human progress reduces lifespan, though not health span always. People have shorter lifespans but longer health span in advanced countries. Technological evolution can lead to better longer health spans by some calorie restriction and chemical mimetics - fooling the body to believe shortages of calorie restriction are likely.
The mTOR (mammalian target of rapamycin ) is hence a puzzle. Every technological advance in nutrition and comfort from technology boosts it. Eating proteins boost mTOR! If you look great, your mTOR has been boosted. Every comfort boosts it. But it devastates aging. Anyone shooting for long life must stop its growth. There is a boost link from igf-1 to mTOR. Boosting gif-1 improves age but reduces it also from the mTOR link in Akt pathway. In words, Growth Hormone GH boosts age but also reduces it by instantiating diabetes. Dr. Fahy fixed it by GH+ metformin+ DHEA, and I will GH+ DHEA+L ow-rapamycin in the self trial. The point is the extreme difficulty of dietary restriction and my desire to look fit, not thin weakling as all aging masters (Sinclair, De Grey, Fahy} look. mTOR is the center of the puzzle. Every good consequence of technological evolution {food, muscle, comfort against time, improved communication saving not just effort but time as well}. A master Sinclair speaks great things for cold (all morning treks in the snow without a shirt, chest bare), combination bath Sauna/ice-water, one food/day, etc. These are not my reason for living long. I am an animal crafted by biological evolution primarily selected by biological evolution for escape from predation before fruitful multiplication.
It matters not that the very growth processes of the first 20 years have turned against me. I believe in Chemical mimetics. I believe in some aerobic exercise. I believe in some anerobic (weight lifting) to fight sarcopenia. Both reduce mTOR. No mimetics. Sinclair uses an old lack of knowledge. I refuse to look weakling like the masters.
Inhibiting TOR boosts regenerative potential of adult tissues
Rapamycin prevents age-related loss of stem cells
Summary:
It is a very big step for me – criticizing Dr. Sinclair! Lack of knowledge at the time of habits means he boosts chemicals with proven dietary restrictions. His latest improves by adding spermidine senolyte. He still takes ALA. He talks of biological evolutionary adversity mimetics for survival in lean periods leading to genes necessary for lean periods. Our technological revolution (= tech-evolution) means no more lean periods.
There is a paradigm shift in my thinking –
Rather than study animals that age quickly, Prof Steven Austad believes animals that age slowly may hold the answers to human longevity.
In particular, it expands on the idea that billions of years of evolution may have already solved many of the challenges of aging and longevity in some cells in some animal at top of its food chain or very difficult to hunt that we are currently trying to understand and overcome.
Focus on slower aging animals
After working on opossums and other animals for a few years, Austad decided that what the aging field really needed was to study animals that age slowly, rather than those that age rapidly.
Austad cites the example of bats – creatures that are often even smaller than mice and yet live for decadesin a state of good health. While not considered “exotic” from a zoologist’s perspective, bats are certainly an unfamiliar sight for most laboratory scientists.
“Now we have the genome sequencing technology and all kinds of things to look at which genes are turned off and on, and in which tissues,” he says. “What I think we need is a kind of Manhattan Project to focus on a few of these species that don’t age, or age very slowly, and figure out how they do it.”
“There’s also Calico, who don’t like to talk about what they’re doing, but they have a big investment in naked mole-rats, which I also think is a very interesting animal.”
Here’s even more exciting facts to add: Bowhead whales (Balaena mysticetus) are the longest living mammals. The Arctic and subarctic whales comfortably live over 100 years, and may live more than 200 years, according to the National Oceanic and Atmospheric Administration (NOAA).The whales have mutations in a gene called ERCC1, which is involved with repairing damaged DNA, that may help protect the whales from cancer, a potential cause of death. Furthermore, another gene, called PCNA, has a section that has been duplicated. This gene is involved in cell growth and repair, and the duplication could slow aging, Live Science previously reported.
Rough eye rockfish (Sebastes aleutianus) are one of the longest living fish and have a maximum lifespan of at least 205 years, according to the Washington Department of Fish and Wildlife. These pink or brownish fish live in the Pacific Ocean from California to Japan. They grow up to 38 inches (97 centimeters) long
Greenland sharks (Somniosus microcephalus) live deep in the Arctic and North Atlantic oceans. They can grow to be 24 feet (7.3 meters) long and have a diet that includes a variety of other animals, including fish and marine mammals such as seals, according to the St. Lawrence Shark Observatory in Canada.
A 2016 study of Greenland shark eye tissue, published in the journal Science, estimated that these sharks can have a maximum lifespan of at least 272 years. The biggest shark in that study was estimated to be about 392 years old, and the researchers suggested that the sharks could possibly have been as much as 512 years old, Live Science previously reported. The age estimates came with a degree of uncertainty, but even the lowest estimate of 272 years still makes these sharks the longest living vertebrates on Earth.
Turritopsis dohrnii are called immortal jellyfish because they can potentially live forever. Jellyfish start life as larvae, before establishing themselves on the seafloor and transforming into polyps. These polyps then produce free-swimming medusas, or jellyfish. Mature Turritopsis dohrnii are special in that they can turn back into polyps if they are physically damaged or starving, according to the American Museum of Natural History, and then later return to their jellyfish state.
The jellyfish, which are native to the Mediterranean Sea, can repeat this feat of reversing their life cycle multiple times and therefore may never die of old age under the right conditions, according to the Natural History Museum in London. Turritopsis dohrnii are tiny — less than 0.2 inches (4.5 millimeters) across — and are eaten by other animals such as fish or may die by other means, thus preventing them from actually achieving immortality.
https://www.livescience.com/longest-living-animals.html
We don’t have to choose between long-lived and short-lived species, both have utility. As does studying short and long-lived humans and even studying the great apes and the DNA of Neanderthals, Denisovans, and other early humans. Just studying a large number of drugs and supplements we already have in tissue studies can easily be helpful. Or even engineering solutions not present in nature.
We haven’t been studying any of these areas long enough to justify favouring one approach over the others.
We also likely have to find solutions for all the ways we age rather than just looking at methylation, or telomeres, or the thalamus. Or a dozen other topics. Then there is prevention and repair, which, of course, are not the same.
The mTOR puzzle
mTOR is basic to chemical mimetics that allows us comforts of tech-evolution within the limitations of bio-evolution. Given the pace and quality of scientists at Musk’s neuralink, I expect brain downloads before the century is out and be alive to then! Never mind the 512-year health span of sharks. Maybe, humanity will go beyond Dr. Sinclair and not do mTOR reduction methods.
A remarkable paradigm shift is in how to get end-less life!
1. Standby for fertile sci-fi imagination from me!
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