Breaking the code of aging: the new science of aging and what it means to stay young

In his new book, Breaking the Code of Aging: A New Science on Aging and What It Means to Stay Young, Josh Mitteldorf, who studied aging for decades and wrote about it on his website, studies the science of aging and sets up his own theory of why we, and literally all organisms are harder bacteria are aging. (Co-author of the book is Dorian Sagan, but Mitteldorf's theory).

This scientific book of the year, the best I've read lately.

Mitteldorf is an expert in evolutionary theory — albeit an astrophysicist — and promptly and skillfully expounds and criticizes several current theories of aging. As a result, he proposes his own radically different theory. He is very persuasive. Whatever the fate of his theory, he brings enough evidence both for and against other theories, which I think his theory deserves to be considered.

Spike in the side of evolutionary theory
')
Aging was a thorn in the side of the theory of evolution from the very beginning. Even Darwin knew and understood this and did not see a way to incorporate aging into the theory of evolution.

Aging is a mystery to the theory of evolution, because aging clearly lowers biological fitness, causing lower reproduction and higher mortality. Why did evolution not cancel it, or not allow it to appear?

If the body does not age, it will seem to be an advantage: it will never die and will continue to be fruitful throughout life; therefore, the longer the organism lives, the more descendants it will leave, and the more adapted in terms of evolution it will be.

Indeed we see it in some organisms. Lobster, for example, obviously does not age, but grows more and more prolific with the passage of life. (The record weight of lobster was 20 kilograms.) Mitteldorf describes several species of long-lived mollusk, which does nothing except that it eats and lays eggs a million a day.

But man and most animals are aging. Animals in the wild have a greater risk of dying from predators and infections as they get older. Why has evolution not stopped it?

One old idea, by Peter Medawar, is that the power of natural selection decreases with age. If the body is aging and then dying, any genes that were involved in aging, have already been transferred to descendants. The idea is that some genes that cause aging are also needed for growth and reproduction. Hence natural selection is unable to eliminate these aging genes.

The idea of ​​Medawar leads us to three modern theories of aging.

Accumulation of mutations : Genetic mutations are always present in the population; in another context, it is known as a genetic load. If the mutations are not strong enough to cause death, but only cause a 1% decrease in fitness, then these genes can remain in the population for a long time. Essentially, natural selection does not have enough time to get rid of them. An example would be the ApoE4 gene, which raises the risk of dementia and cardiovascular diseases.

But even 1% of the difference in fitness, as Mitteldorf says, "is far away to be invisible to natural selection." Older animals do not die due to aging usually, but they die more often from predators and diseases than young animals. In some arctic species, 60% of deaths in the wild can be attributed to aging. Natural selection must be able to eliminate the genes causing these enormous death counts, and do it quickly.

Antagonistic pleiotropy : Some, perhaps most, of genes have several functions, and this theory suggests that the genes that provide carefree adolescence cannot be weed out, as they cause aging. As an example, this may be the hormone IGF-1, which is involved in both aging and growth. Newborn mice that do not have this hormone will soon die, but its increased content in the body of elderly people correlates with cancer and increased mortality.

IGF-1 is a growth hormone . A confirmation of its important role in aging is Laron syndrome, a form of dwarfism caused by a mutation in the growth hormone receptor. People with LaRona syndrome do not grow to their proper size, but they are less likely to develop diseases accompanying aging (for example, cancer and diabetes).

mTOR . This is a protein that has been talked about in connection with the benefits of fasting. It supports the processes of glucose cleavage and protein synthesis, but it blocks autophagy - the digestion of damaged proteins and organelles. When fasting, there is a shortage of energy, mTOR stops working, autophagy starts and the cell updates its contents and “work tools”. This seems to be related to the fact that restricting calorie intake prolongs the life of the most diverse organisms.

Insulin Its main function is to force cells to capture glucose from the extracellular environment, that is, to increase energy intake. In addition, it enhances the production of a number of hormones associated with growth and development, and the deposition of fat reserves.

Mitteldorf describes the work of Michael Rose, who paired the fruit fly for the long-lived in order to see what happens to fertility. In theory, if he chose a long-lived fly and mated it for longevity, their fecundity should decrease, giving antagonistic pleiotropy. But this did not happen; their fecundity went up. So it seems there is no reason why nature cannot share the function of fertility with aging.

Disposable soma : Resources, usually in the form of food energy, are always in short supply, as the theory says that the body must allocate resources for different needs. Repairing damage at the cellular level is one of these needs and an important part of aging, so that if the body cannot repair all the damage, aging happens. So if resources are in short supply, the body allocates them preferentially to growth and reproduction, and essentially makes itself grow old.

Striking evidence against theory is calorie restriction, the most reliable life-extending intervention in laboratory animals. When they literally go hungry, animals can live 50% longer than normally fed animals. If the lack of resources causes aging, we might expect the opposite. If you eat more, you will live longer; but this is clearly not the case. Eat more, die young - and this is true for literally every kind of organism that has been tested.

Exercise is also true - if damage and repair is critical for aging, exercise will age you faster. Exercise causes damage — they also force animals, including humans, to live longer.

Gormesis

Both calorie restriction and exercise are examples of hormesis in which the application of stress or toxins induces better health and a long life. The body not only repairs the damage, but becomes stronger and healthier than before.

Gormesis central effect in the theory of aging Mitteldorf. As he says, it seems that the body already has anti-aging abilities that it simply does not use in simple times. The body is fully capable of slowing down aging when conditions are right.

Aging is not damage that the body does not control or natural selection that cannot eliminate. This is not due to lack of resources or pleiotropic genes. Not
Aging is programmed.

Program aging and group selection

The theory of programmed aging is confronted directly with the neo-Darwin theory of evolution, which is a theory of current thought in biology.

Neo-Darwin theory says that natural selection occurs at the level of genes, and only favors the individuals who carry these genes.

Mitteldorf's theory of programmed aging relies on group selection, a concept which, according to most scientists, does not exist, or if it does, it is not strong enough.

Consequently, my description of Mitteldorf's theory is so radical, from the fact that he fully relies on neo-Darwin synthesis, and the scientists who support him.

In this light, more interesting is the fact that Mitteldorf's mentor was another proponent of group selection, David Sloan Wilson, author of the Darwin Cathedral book workshop: evolution, religion, and the nature of society.

The programmed theory of aging regards aging as a “suicide program” that does not benefit the individual, but which brings great benefit to the group. The body picks up genes that cause inflammation and other forms of damage, which leads to aging and death. Aging is a purposeful effort on the part of the body, and not what it is trying to avoid.

Why do organisms do this? The advantage of the group must be very powerful in order to undo the harm to the individual. And indeed, this is so, according to Mitteldorf.

Organisms age to avoid extinction.

In any successful group of organisms, it seems that the group can easily regulate the environment and succumb to hunger or other reasons.

All animals in varying degrees are predators, depending on other forms of life for food, and if the animals are too successful, they risk starvation or epidemics and the subsequent disappearance of the whole group.

Aging is a way of organisms buffering the population. In good times, with abundant food, the body grows old and some of them die, thereby keeping the group within its environmental constraints and in accordance with its ecology. The band is thriving.

In bad times with fewer resources available, aging slows down. This species does not want every member to die immediately, from hunger or some other reason. He wants to avoid extinction, an event that means the death of each gene carried by a species. When the crisis is over, aging is resumed.

Criticism

Mitteldorf supplies a lot of evidence of his theory, and this makes reading fascinating. Reading it, I thought about several objections, which was not easy, as the author convinces. Note that I am not an evolutionary biologist.

Aging seems too erratic to become a “suicide program”. If you think about how aging causes harm, illness and death, how can there be many sources of these things? One gene that caused death would be much simpler, and the fact that aging, apparently, has multiple genetic roots, makes you wonder how this can happen as a result of natural selection.

Admittedly, this objection probably depends more on taste in theories than on empirical support.

Another objection is that just passing the time seems to be associated with some aspects of aging, such as iron accumulation or exposure to microbial antigens.

Iron seems to be a good example of pleiotropic effects: it is necessary for growth and reproduction, but it causes aging. In addition, natural selection may not be able to eliminate its effects on aging. Women with a higher iron content are more fertile, which can fuel the effect of natural selection on iron, which causes aging after a person already has children.

Detection of the antigen comes from infectious agents and is the main cause of inflammation during aging. The longer we live, the more antigens we are exposed to, and in fact, those who are exposed to more diseases die younger, that is, they age faster. But perhaps the body can not remove inflammation, since we need it to fight pathogens.

Conclusion

Hacking the code of aging is the best book I've read this year, and it must be read by anyone interested in aging or evolution and biology. Mitteldorf skillfully makes its way through evolutionary theory, its history and the biology of aging - he even knows his own path in the field of ecology.

At the end of the book, he discusses the prospects for anti-aging research, as well as what, in his opinion, is the best way to slow down aging, which we have now.

His ideas on slowing down aging, I am glad to say, are very consonant with what I have stated on this website: exercises, intermittent fasting, supplements such as berberine and curcumin, aspirin, and much more. (I think he should have mentioned iron.) There are technical developments on the horizon, such as telomerase therapy, which have great prospects for achieving the root mechanisms of aging.

Therefore, go and read this book.

Translator's Note

The experiment was completed on 15,000 mice and 1050 molecules, on the average and maximum life extension in the Jackford laboratory of Stanford University. The greatest results showed
Magnesium,
Inulin (available in Jerusalem artichoke)

and these extracts and substances:
Lemon or lime extract, - Lemon Extract
DTPA,
EDTA,
St. John's wort extract, - Hypericum extract
Hyperforin, Hyperforin
Ginkgo bilogoba extract, - Ginkgo biloba extract
Ginkgolide A or B, - Ginkgolide A or B
Vitamin C, Vitamin C
Ascorbic acid 6-palmitate, - 6-palmitate ascorbic acid
Pantothenic acid (vitamin B-5), - Pantothenic acid (vitamin B-5)
Niacinamide, - Niacinamide
Allicin (garlic) - allicin
Lactobionate
Melatonin - Melatonin
Metformin - Metformin
L-Dopa,
extract Mucuna beans (Mucuna Dopa), - Mucuna beans extract
L-Histidine, - histidine
Quercetin - Quercetin
Curcumin, - curcumin
L-Glutamic acid, - L-glutamic acid
succinic acid - succinic acid
N-Acetil Cysteine, - N-acetylcysteine
Green tea extract, - green tea extract
Epigallocatechin-3-gallaye, - epigallocatechin-3-gallaye
Glutathione, - Glutathione
Aspirin, - Aspirin
Salicylate, - salicylate
Glycine, - glycine
Resveratrol, - Resveratrol
Genistein - Genistein
Garnosine, - Garnosin
Rapamycin, rapamycin
Lipoic acid - lipoic acid
Taurine - Taurine