Maria Konovalenko

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Politically important article in Science Translational Medicine

The authors are: Michael J. Rae, Robert N. Butler, Judith Campisi, Aubrey D. N. J. de Grey, Caleb E. Finch, Michael Gough, George M. Martin, Jan Vijg, Kevin M. Perrott, Barbara J. Logan.

The article was published on July, 14. The authors advocate that funding of scientific research is substantailly increased and interventions for aging humans are developed.

Progressive accumulation of aging damage is the physiological cause of numerous age-related pathologies, loss of functionality and increased mortality. Aging places an unprecedented economic and social challenges, as the global increase of medical costs and decreased national workforce's ability. Interventions to to retard, arrest, and even reverse aging damage need to be developed in order to prevent our society from experiencing these catastrophes. 

I'd like to pay more attention to the particular research directions. To my mind the authors focused on some really important areas. I put them here in a form of a list, I guess it's better if one adds numbers.

1. Loss of Proliferative Homeostasis: embraces

1.1. age-related hyperplasia (including excessive proliferation of osteoclasts, interstitial fibrosis, and, above all, cancer),

1.2. loss of tissue renewal through stem cell attrition (due, e.g., to cellular senescence, apoptosis)
or atrophy (from systemic endocrinological and signaling changes)

1.3. as well as aberrant differentiation (e.g., accumulation of mesenchymal adipocyte-like cells in aged
tissues, incomplete myocyte development in skeletal muscle, osteoblast-like
differentiation of calcifying vascular smooth muscle cells, adipogenic transformation of
thymic stromal cells in thymic involution, etc)

Low calorie diet and the brain

I am always very pleased to see new research results in the "misterious" area of neurophysiology of aging. One of the lastest is published in the July 28 issue of the Journal of Neuroscience. A group of scientists from the Washington University School of Medicine found that the mediator of diet restriction, SIRT1, helps mice survive when the food is scarce.

Researchers compared two groups of mice, one that had elevated levels of SIRT1 in the brain, called BRASTO, and a SIRT1-deficient group. BRASTO mice were much more active after fasting, also they were able to maintain their body temperature. Investigators link these findings to the role of SIRT1 in the hpothalamus region of the brain. During diet restriction SIRT1 enhanced the production of a specific neural receptor in the hypothalamus involved in regulating metabolic rate, food intake and insulin sensitivity.

This is the evidence of an indirect link between SIRT1 expression in the brain and life extension. Since SIRT1 seems to be one of the key mediators of responce to diet restriction, and diet restriction was shown to increase lifespan in different model animals, SIRT1 may contribute to life extension effect of low calorie diet. More information can be found here.

The meaning of life is to live

I have just come back from a totally great vacation in Turkey. I stayed at the Adam&Eve hotel in Belek. Had a wonderful time! 

Now I'm going to the Systems Biology of Aging meeting in Newcastle, UK.

  

The Blocking Point

Why is it actually that life extension research is funded so insufficiently? Well, here is why. Of course, there are people who have money. And they're not averse to thinking about scientific research. It may turn out to be quite a useful thing. Moreover, one can make money out of it. Yes, these people would love to have a magnificent innovation, a biotech company. They tell the scientists: “Bring us the business plan! – We’ll consider it.” And here’s the thing… If the idea is truly new, there is no business plan; there’s not even a guaranteed result. The planning of the innovative work itself turns out to be an extremely hard and expensive task. And a good scientist is always busy, so he cannot really create beautiful presentations, and he also has absolutely no idea that more scientists need to be engaged in this kind of work, and that the main costs will be the organizational ones. So, this means that the investor wants some tremendous work from the scientist and only then would he make a decision about the money. That is why large organizations that announce grants receive bad proposals, because nobody invests in the creation of the project proposal, or because the proposal is some really old stuff that, for some reason, makes an impression.

Just imagine, an investor wants a huge, 600,000 square foot, shopping center to be built, and he tells the architects: “Well, guys, just give me a project with all the services, utilities, calculations, and logistics, and then I’ll see whether or not to finance the construction and your work or not.” The architects would faint after hearing such a wonderful proposal. Or, they would give the investor some old project that they have already done, but, in our case, haven’t been able to create an innovation.

What needs to be done? First of all, one should ask the scientists to write proposals for money. He should also understand that a lot of what they’d write just wouldn’t be satisfactory. There’s this thing here: a sucessful scientist is overwhelmed with work for the next 3 years, and he wouldn’t stand in the line in front of the investor’s door. One has to find the scientist and persuade him to cooperate. Then comes the reviewing part (it’s another story about how to get impartiality). Then comes the choice of the project. And still, it will be risky. Here I'd like to say a couple of words about the necessety of a complex and systems approach, but maybe another time.

H+ Summit in Boston

The  H+ Summit took place in Boston on June 12-13 at the Harward University Science Center. Here are some photos that I took at the meeting. Above pictured are the organizers David Orban and Alex Lightman introducing Andrea Kuszewski, who worked on enhancing the intelligence of the audience.

Transhumanism

Transhumanism is a philosophical movement which implies that the goal of every person is the development of scientific and technological progress dedicated to increasing the viability of a person, radical life extension, and providing unlimited broadening of the individual’s potential.

Transhumanism is a concentrated expression of common sense.
Everyone has got their own values – family, kids, art, love, beauty, freedom, money, traveling, sex, power… But they all make sense only if the person is alive. The basic condition for existence and implementation of all these values is life. The most sensible strategy for every one of us is radical life extension through rational, scientifically provable methods.

Transhumanism is striving towards the ultimate justice and happiness.
There is nothing more unfair than death. Death, senility and disease make a person miserable. The fight against disease and suffering, and for the radical extension of human life, is the fight for justice and happiness for every person.

Transhumanism is a natural expression of the human entity.
The essence of evolution is in development, and a human being represents this at its greatest. It’s in their nature to strive towards broadening their potential, expansion and increasing the scope of their personality.

Transhumanism is an acceleration factor of human evolution.
Life, in the first place, is a form of organization of matter aimed at self-preservation. Life is an anti-entropic process. A person is allotted the ability to self-improve. They can gain new knowledge and skills, and improve them upon using their own body. Human evolution is not only happening in the biological plane, but also in the scientific, technological, and social ones. This refers to the evolution of personality in the first place.

Transhumanism is the resultant vector of progress.
This history of mankind is a history of growing potential and increasing  longevity. Everything that makes our lives better, more comfortable, replete and longer is a result of this progress. Still, there are risks and dangers associated with the development of science and technology. They represent the forces of regress and entropy. These phenomena should be considered as the unsolved problems of progress. Transhumanism actualizes the goal of accelerating scientific and technological progress in the interests of every person.

Transhumanism is striving towards the preservation of civilization.
One of the problems facing mankind is global risks, events possibly leading to death of civilization. It is necessary to calculate these risks and withstand the implementation of the negative scenarios. Transhumanism sets the goal of indestructibility of mankind. 

Transhumanism is a clear understanding of the unconditional hierarchy of goals.
Given limited financial and intellectual resources, it is essential to distinguish the more important tasks and focus on their implementation. Certainly, the most crucial goal is radical life extension. Flying to Mars, for example, is important for progress, but is less urgent at the moment, because people are dying from senility and diseases.
The fundamental research in the area of life extension should be number 1 on the rating list of the goals of civilization.

Transhumanism is the coordinator of scientific research.
The prospective directions for developing scientific methods and technologies for radical life extension are: regenerative medicine, personalized medicine, preventive medicine, neuroscience and studying the influence of high nervous activity on the processes of aging, neuromodeling, studying the biomarkers of aging, genetic and epigenetic regulation, research into cell differentiation and cellular patterns of aging, cell and hormonal therapy, the Physiome Project, tissue engineering and creation of artificial organs, development of the methods of studying molecular biological processes, development of the methods of cryopreservation of large biological objects, mathematical modeling of aging, creation of artificial intelligence, evolutionary biology of aging, studying the synthetic and fractal theories of aging, and also the theory of consciousness, development of futurology, and studying the Technological Singularityphenomenon. Transhumanism is actively supporting and advocating for the development of these fields. 

Transhumanism is an active life position.
Given the limited time frame of a person’s life, it is shortsighted to passively wait for the achievements of progress. It is necessary to do everything possible to extend one’s own life – to use disease prophylaxis methods, lead a healthy lifestyle, increase one’s own scientific competency, actively promote scientific research relevant to the goals of transhumanism, advocate for its ideas, and support cryonics as the means of future recovery of life activities for dead people.

Transhumanism is striving towards broadening the human potential.
The following is vital for a person: enhancement of the intellect, spirit, and will, singleness of purpose, achievement of the freedom of a personality from biological vessels, and an increase in the level of the development of space and energy. The goal of transhumanism is for every person to have these possibilities and to be able to use them to the fullest extent.

Transhumanism is the expression of tolerance.
If someone doesn’t  want to live longer, they can refuse to use the achievements of this progress, like the 200,000 Amish (Christian Mennonites), who decided to freeze their technology at the level of the 19th century. Authority in a future society will be necessary only for the purposes of preventing of the global risks and providing to every person the possibility of living for as long as they wish for; the rest of the issues should be regulated at the level of professional communities.

The main question in Biogerontology

There's this quite simple idea: to take two species similar in size and basic biology, but having a substantial difference in longevity, and figure out what’s the reason for this difference. What are the distinctions in the mechnisms of aging and stress resistance? It’s desirable to carry out this work in various species. However, not a lot of people are excited about this simple idea. Even the genome of the famous naked mole rat has not been sequenced yet, although many people believe it’s got “negligible” senescence.

For now all that we have is negligible funding of evolutionary-comparative biology of aging. Moreover, previously obtained results are put into cold storage.

In 1962 George Sacher began laboratory breeding of wild-caught house mice (Mus musculus) and white-footed mice (Peromyscus leucopus) trapped near the Argonne Laboratory site in northeast Illinois. The maximal lifespan of the white-footed mouse turned out to be more than 8 years, contrary to 3,5 years in either wild-caught or laboratory house mice. Sacher’s laboratory publiched about a dozen papers comparing house and white-footed mice, as did Ron Hart’s laboratory in the National Center for Toxicological Research.

There's no need to say that George Sacher was given grants mostly for works in the area of radiological protection, and aging research was mostly funded by means of the lab's own resources.

Since the beginning of the 1980s research was just middling, but still something was found out.

Below are some data from the works of Ungvary et al. and Labinskyy et al. Basicly this table shows the major known differences between the species. The autors claim that these data correspond with the oxidative stress theory of aging.

Still a lot of questions can be addressed to the white-footed mouse. For example, what is the destinction in the stress resistance mechanisms? What's with its regeneration capacity? What if we compare it with the naked mole rat? And here comes the main question in Biogerontology. Why is the research into the fundamental mechanisms of aging so scarcely funded?

Regenerative Medicine Roadmap 1.1

Here is the updated edition of the Roadmap to Regenerative Medicine; the first one can be found here. Cell therapy and tissue engineering are described in more detail, than the rest of the scientific issues. I welcome everybody to take a look and add what's missing and/or change what's wrong. I'd also like to note that the organizational issues aren't described at all, but this is probably the most important part of the roadmap. There should be an implementational plan of how exactly the Roadmap should work included in the organizational part. To do that, we need to address the specialists in the given fields.

But at least for now the question is - what's missing in the scientific part?

You can download the Roadmap here.

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?