Main questions of Biology of Aging

Here
are the main questions in the Biology of Aging. I suggest that the specialists
should extend the list of questions. And maybe, formulate the problems in more
detail. Everybody is welcome to express their opinion and suggest some
answers.

1. What are the mechanisms responsible for the differences in life expectancy within one species and between species?
2. Why do experimental impacts, like caloric restriction, delay the
onset of a number of age-related physiological and pathological changes
and increase the average and maximal life span in animals?
3. What is the relationship between aging and pathology?
4. At what stage of evolution did aging emerge?
5. How did the mechanisms of aging and anti-aging evolve?
6. What are the mechanisms of relationship between aging of an organism and aging on cellular level?
7. What is the reason for the existence of species with negligible aging?
8. How are reproduction and lifespan interrelated?
9. What is aging?
10. Why is there a decline in regenerative potential of an organism over time?
11. What is the role of epigenetic regulation during aging?
12. What is the role of inflammation in aging processes?
13. What is the role of genomic instability in aging processes?
14. What interventions in aging processes could extend the maximal lifespan of model animals and humans?
15. What is the effect of aging on the cells’ and organisms’ energy supplies and vica versa?
16. What is the role of the neuroendocrinal system in the regulation of aging processes?
17. What is the distinction of centenarians as compared to the whole population?
18. How relevant to humans are the results of life extension research on model animals?
19. What is essential for creating the unified synthetic theory of aging?
20. How did animals with negligible senescense evolve?
21. What are the factors influencing differences in the rate of aging among individuals?
22. What are the mechanisms of aging in cancer cells?
23. What is the relationship between aging and oncogenesis?
24. When does aging begin in humans?
25. When do manifestations of aging begin?
26. What are the molecular biological mechanisms of regeneration during sleep?
27. What is necessary for the creation of an exhaustive list of biomarkers of aging?
28. Can neurogenesis be stimulated?
29. What are the mechanisms of how higher nervous system activity influences the mechanisms of aging?
30. What are the factors defining the rate and efficiency of stress responses?

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“Magical” regeneration in MRL mice

I just couldn’t walk past this article in PNAS about the miracles that happen to one strain of lab mice – MRL. These guys can fully close ear holes made for labeling purposes in order to mark a mouse for its whole life;  in these animals the holes turn out to be just temporary. The wounds close without scarring, and brand new cartilage, derma, epidermis and hair are formed. And the rest rest of the mice could wear earrings, if only there were any animal jewellery!

Another striking thing is that this feature was noticed 9 years ago, when the same group of researches published a paper telling how MRL mice can heal wounds on their hearts, leaving hardly any scars. As early as in 2001, it was shown that these mice can heal themselves from myocardial infarction after-effects in 60 days. But for some reason the molecular mechanisms underlying these miracles haven’t been studied until now. So, here they are.

Why radical life extension is possible

1. There are no physical laws prohibiting radical life extension
2. The lifespan of model animals has been successfully increased in many labs
3. There are animals with negligible senescence
4. Scientists are able to grow human tissues and organs
5. Scientists are able to create artificial human organs
6. The human lifespan is constantly increasing due to implementation of emerging technologies
7. Many scientists in the world who study the fundamental mechanisms of aging state that human life can be radically extended
8. Arguments against the possibility of life extension resolve themseives solely to the inexpediency of human life extension
9. A lot that was considered science fiction in the past has now been achieved by mankind. Cloning and the rudiments of artificial intelligence are today’s reality.
10. Striving towards self-preservation is the main feature of living matter. Life extension is, to a large extent, an evolutionary task for our consciousness.

Bubonic plague

Almost every time the conversation drifts to fighting aging, the majority of people lose their common sense. Here’s how a typical dialog about aging looks like, but the word “aging” is substituted with “bubonic plague”. This takes place in the city of “N.”

Bubonic plague fighter: There’s a huge problem in our city – we’ve got an epidemic of bubonic plague. If we do nothing, everybody will die in the throes of bubonic plague.

Inhabitant of the city: Let’s take a look at the problem from another point of view: if nobody dies from bubonic plague, our city will be overpopulated.

Bubonic plague fighter: We don’t have a problem with overpopulation right now, but we do have one with bubonic plague. If the people are healthy and sane, they will be able to stop overpopulation from happening – we can domesticate new land, limit child birth, and build really big houses. I’m telling you, we don’t have the problem with overpopulation now, but half of the inhabitants have fever, and they are dying from bubonic plague. We need to spend resources on finding a vaccine.

Inhabitant of the city: People don’t only die from bubonic plague. For example, the butcher was driven over by a cart yesterday, and on Third street a boy died from pneumonia. What do we do about that?

Bubonic plague fighter: But still, the great majority are dying from bubonic plague. Their bodies are covered with ulcers, and their inner organs are affected. This is a major issue. It needs to solved in the first place.

Inhabitant of the city: People have always been dying from bubonic plague. Millions of people died from it in our town and in other cities. This is natural. You shouldn’t argue with your fate.

Bubonic plague fighter: Then why do we try to conquer other diseases, but not the bubonic plague? If there were a vaccine, people would not refuse it! People have always tried to do what’s best for them. Now that’s natural.

Inhabitant of the city: But bubonic plague cannot be defined as a disease, because nobody is trying to overcome it, and there’s no cure for it. This is what nature gave us. It cannot be cured.

Bubonic plague fighter: Scientists have some positive results, but they haven’t got enough money to enlarge the scope of research. More labs need to be built.

Inhabitant of the city: Isn’t it going to be that only the wealthy people would be able to afford the drug?

Bubonic plague fighter: Let’s first create the drug and then think how we can make it affordable for everybody. By the way, look, you have some kind of a strange ulcer yourself.

Inhabitant of the city: Now all the people that live in our city are extremely active, because they know they will soon die from bubonic plague. We are very successful at different crafts; we built a theater; we have big plans for organizing a sports championship. The progress would stop if there had been no bubonic plague. We wouldn’t need to rush – it would be boring to live.

Bubonic plague fighter: If you are covered with ulcers and spit blood all the time, you’ll be bored to live for sure. When a person is healthy, it’s obviously much more interesting and joyful for him to live.

Inhabitant of the city: You’re saying this because you’re afraid of bubonic plague yourself. And I’m not!

Bubonic plague fighter: It takes a lot of courage to try to solve the problem, but not to say there is none.

Inhabitant of the city: But what can I do? Nothing depends on me.

Bubonic plague fighter: You can persuade other people, and you can show a good example – give your own money to the scientists. The mayor needs to be persuaded. You have to act, do something. But you must want to act in the first place.

Inhabitant of the city: I killed a couple of rats in my house and I don’t eat meat. I’ve always been telling other people that rodents have to be destroyed because they spread infection.

Bubonic plague fighter: It’s not enough. We can chase rodents until the end of time, however a vaccine has to be developed in the first place.

Inhabitant of the city: There are frauds who sell cure from bubonic plague. One can also use make up for the ulcers, so they won’t be seen.

Bubonic plague fighter: The fact that there are swindlers and cosmetology does not cancel the need to fight bubonic plague. Are you ready to make the effort to do it?

Inhabitant of the city: You are doing such a great job. But I can’t deal with fighting the bubonic plague. I have lots of my personal problems. I must build a house for me and my kids to live in.

Bubonic plague fighter: I won’t be able to fight bubonic plague on my own. Everyone has their own goals, problems and tasks, but bubonic plague is going to knock on everybody’s door and everybody is going to rot alive. The problem will not be solved until we unite.

About epigenetics and aging of the brain

There’s this fascinating article published in Science that I decided to illustrate. This is my retelling of the story.

15 mistakes of an investor who funds research on life extension

1. Despite everything that I am going to write further, the biggest mistake of an investor is to think that someone else is going to fund the search for interventions into human aging such as growing and creating artificial organs. Despite quite a large amount of news on this topic, there are no breakthroughs yet, and that’s mostly because of a lack of money and good management. I’d like to note that the capitalization of a dead investor is equal to zero, and it’s only research into life extension that can help them thrive on and on.

2. So, one day, having heard the scientists discovered something, an investor thinks: what’s that about? And the very same second when he thinks “what’s that about,” there’s already a man in front of him with a totally great proposal on life extension. Depending on how lucky the investor is, it may be: a good scientist, a bad scientist, a fraud, or an insane person. In any other case all the life experience of our investor would have told him that he at least shouldn’t deal with an idiot. But not in this situation, he starts to think that this is how scientists look like.

3. Depending on who happened to be in front of our investor – a good scientist, a bad scientist, a fraud, or an insane person, the vis-à-vis starts to say the same words: “I’ve got a great drug, it works, we’re almost there, give money fast, the world is going to kneel down in front of us, here are the papers, take a look, there’s no such thing in the world like this”.

4. Even if it’s a good scientist, the drug wouldn’t work anyway, besuase of two reasons: the solution to the problem of aging is much more complex than we assume, and if there had already been something that worked, then everyone would know about it. And the good-natured collegues would have had their patents for a hundred years ahead.

5. Since the lives of the investor and all of mankind are at stake, he begins to fund immediately. It’s a good thing if it’s an insane person who came along – these guys ask for less money. Even a free meal means a lot to them. But they are very harmful when you waste time on them and when they destroy your mind with their schizoid instructions.

6. The very same minute when this whole affair is started, here comes another man with an idea none the worse, maybe even a better one. Since our investor was raised never to put all his eggs in one basket, this new partner gets a blank check.

7. Then something terrible happens – now everyone knows about our investor. He in turn immediately learns about the existence of telomeres, lysosomes, recombinant proteins, peptides, radial glia, mitochondia, pineal gland, Aubrey de Grey and whatnot, and thinks that the world is going crazy.

8. The situation is complicated – a management team is hired, whose competency is close to that of an infusorium. A dreadful fight now takes place to have the investor’s ear.

9. Then comes the brilliant organizational decision: “Let’s gether the best minds together in one place and they will create the strategy to quickly solve the problem!”

10. The best minds are used to getherings, but they are not even capable of agreeing on what exactly they are going to discuss. That’s why everybody speaks about his own unique passion.

11. Our investor is already old hand with his own scientific view. He attends scientific conferences. If he’s an introvert, he believes aging is programmed; if he’s an extravert, then in his opinion, aging is due to the accumulation of damage.

12. An office is leased – an organization is created. A huge mailing campaign is going on. Some serious work is being carried out on formulating the mission of the concern, on creating the booklet and the website. It all goes wrong. Everything fails.

13. Trouble comes in threes. The initial investment also did not perform. No results in two years! All we have on our hands is a product that doesn’t contain any sodium chloride. The scientists anathematize themselves.

14. Things go wrong with business too. It goes just as well as fighting aging.

15. Our investor gets disappointed. He thinks there’s nothing that can be done. He starts to like fishing.

To avoid any rumors I have to say I don’t mean anybody in particular. My story is based on the experience of dozens of people from all over the world, whose stories are like copies of one another.
And here comes the homework! What are the mistakes that our investor has made? How should one act right? And I am going to start thinking about «15 mistakes of a scientist…».

About overpopulation

The most common question I get is the one about overpopulation. Not that people are interested in this issue in particular, but when they hear about what I do they immediately ask: What about overpopulation? If people would live indefinitely then there will be just too many people around.
Here is the answer.

1. Overpopulation depends more on the amount of kids in a family, not on lifespan. So, no matter if you prolong your life or not, overpopulation may still happen.

2. Let’s deal with problems as they arise. The numer 1 problem now is aging.

3. Theoretically, the problem is not about the amount of people, but about the limitation in resources. The main one is energy. But we have that covered for the next 8 billion years. I mean the energy of the Sun. And the area of the Earth, including the oceans, is enough for 2-3 trillion people to live comfortably.

4. It’s not like the problem itself cannot be solved: one of the solutions is the limitation of birth, for example, via tax regulations.

5. The worst solution to the overpopulation problem (which does not yet even exist!) is the denial of life extension for the currently living generation.

I believe it’s crucial to find out why, actually, this argument arises. I don’t think it’s because of Harry Harrison’s 1966 book “Make room! Make room!,” about future overpopulation. It’s also not because of his explicit and implicit followers – young science fiction writers and sociologists.

In my opinion, the nature of this argument is close to the arguments against unlimited life extension, like: “this contradicts evolution,” “it’s going to be boring to live,” and is one of the imaginary threats. These threats are created only in one’s mind during discussions about immortalism. As a matter of fact, I don’t think a lot of people are ready to give up their own lives for the sake of “evolutionary needs,” or people refuse to take antibiotics when they’re sick, thinking: “what if I get better and become bored? No, I had better not argue with my destiny.” This doesn’t look like an attempt to learn about the issue! Because, in other cases, people do not even think of such absurd arguments. But having heard this answer, the majority does not make the conclusion that it’s about their lives too and that they have to deal with this knowledge.

I am concerned that these arguments originate from the will to brush off the problem and do nothing to solve it. Everyone has got their own list of troubles and they don’t need one more. Moreover, in the average person’s opinion this issue is not urgent at all. Therefore, our main argument should be that fighting aging is the most important and urgent problem of all!