Monthly Archives: June 2013

What Happened after Human Genome Project – Numbers

hgp_measuresWe now know the molecular basis of more than 4.5 thousand diseases. All of the above is thanks to some brave and very talented organizers who managed to persuade the governments of several countries that spending $3 billion on sequencing human genome is a good thing. Now we need the Human Aginome Project to find out the mechanisms of aging and creating therapies to cure this deadly disease.

Our task is to study the experience of how the Human Genome Project was started and learn from this experience. If you have any information on the beginning of this large-scale project, the people and stories behind it, please,  share.

 

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Understanding Cancer Mutations Makes Testing and Prevention Necessary – Same for Aging

Did you know that there are only 138 mutations that play the major role in making a cell cancerous? Well, 138 found so far, however, the number of these driver mutations inside the genes won’t grow significantly, at least that’s not anticipated. Obviously there are thousands of mutations in cancer cells, but not all of them give the selective grow advantage. This beautifully written review of cancer genetics tells us what the researchers all over the world have learned about differences in normal and cancer genomes. Sequencing technologies are becoming less and less expensive and hopefully very soon we will see sequencing as part of routine clinical testing. Although we are not there yet. The authors of the article provide this outline:

1. Most human cancers are caused by two to eight sequential alterations that develop over the course of 20 to 30 years.

2. Each of these alterations directly or indirectly increases the ratio of cell birth to cell death; that is, each alteration causes a selective growth advantage to the cell in which it resides.

3. The evidence to date suggests that there are ~140 genes whose intragenic mutations contribute to cancer (so-called Mut-driver genes). There are probably other genes (Epi-driver genes) that are altered by epigenetic mechanisms and cause a selective growth advantage, but the definitive identification of these genes has been challenging.

4. The known driver genes function through a dozen signaling pathways that regulate three core cellular processes: cell fate determination, cell survival, and genome maintenance.

5. Every individual tumor, even of the same histopathologic subtype as another tumor, is distinct with respect to its genetic alterations, but the pathways affected in different tumors are similar.

6. Genetic heterogeneity among the cells of an individual tumor always exists and can impact the response to therapeutics.

7. In the future, the most appropriate management plan for a patient with cancer will be informed by an assessment of the components of the patient’s germline genome and the genome of his or her tumor.

8. The information from cancer genome studies can also be exploited to improve methods for prevention and early detection of cancer, which will be essential to reduce cancer morbidity and mortality.

Those 138 mut-driver genes (oncogenes and tumor suppressor genes) can be classified into one or more of 12 pathways. And these pathways can be grouped into three large groups: cell survival, cell fate and genome maintenance. All these things go wrong during aging. The majority of the listed pathways play a role in aging. Naturally, cell senescence is seen as an anti-cancer strategy of the cell. And it works well until it doesn’t. The relationship between these  two processes is not understood completely and more research is definitely needed to answer the question what happens over time. What distorts the balance?

cancer pathways

Cancer is truly an age-related disease. Aging brings decline in DNA repair efficiency and other mechanisms of genome stability maintenance. I think that if we figure out a way how to keep those mechanisms intact, working as good as they do at the age of 16, for example, there’s a good chance we will eradicate cancer, at least the solid tumors. This will be a huge step in increasing human longevity.

I wholeheartedly agree with the authors of the article on the following matter:

“plan A” should be prevention and early detection, and “plan B” (therapy for advanced cancers) should be necessary only when plan A fails. To make plan A viable, government and philanthropic organizations must dedicate a much greater fraction of their resources to this cause, with long-term considerations in mind. We believe that cancer deaths can be reduced by more than 75% in the coming decades (152), but that this reduction will only come about if greater efforts are made toward early detection and prevention.

This idea of prevention is valid not only for cancer, but for aging in general. In my opinion, if we develop the tests, that will definitely include cancer testing, we will be able to see what is happening, what is going wrong on molecular level, and we won’t wait until 90% of the organ is non-functional, until Alzheimer’s have consumed the personality of our loved one, until we feel we can no longer walk up three staircases. We will fight the disease in its infancy, and we will fight aging to remain youthful for as long as we choose to be.

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Great Project Underfunded

Drugs tested 2011

Here’s a great project that needs more funding – Interventions Testing Program – a multi-institutional study investigating treatments with the potential to extend lifespan and delay disease and dysfunction in mice. The idea is simple and elegant: let’s test different kinds of drugs, chemicals, diets, etc. on mice and see whether they live longer and healthier. The study is carried out in three independent labs at the University of Michigan, the Jackson Laboratories, and the University of Texas Health Sciences Center at San Antonio.

One might think this kind of project should allow testing of dozens of different interventions every year for all the humanity to benefit from the results. Hell no! Guess how many compounds are tested early. 4-6, and not more. But we need 3000 minimum! Here’s the list for years 2004 – 2011. The grant description for 2013 states that

It is anticipated that 3-5 compounds will be accepted for study in 2014.

This means that there is very little money available at the NIA for this program. Direct costs of each application may not exceed $500,000 per year and applications may not request more than 5 years of funding. This is so sad, it’s one of the best and meaningful ways of how NIA spends its funding. I wish there will be more attention to the Intervention Testing Program, also more outside sponsors, because the more money there is for these experiments, the closer we are to drugs that slow aging down.

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How can Transhumanism Win?

Frieze-13

Working at the Science for Life Extension Foundation we understood several things regarding tranhumanism and what needs to be done for promoting it.

1. The topics of horror of death and despair of aging are poorly exposed in tranhumanist rhetoric. In the 14th century, in the plague times, death used to be one of the main topics of visual arts. Nowadays the topic of horror of death struggles its way to the surface only on cigarette packs in a few countries of the world. There is an unspoken ban on documentary demonstration of the moment of human death. Death itself is often embellished, heroized and named necessary for triving of other people.

We claim that there is nothing more dreadful than death, and our main goal is to fight it.

We understood that one of the most powerful impact tools are not the rational arguments, but visual images.

We are interested in creating the new art that describes the horrors of aging and death with the aim of increasing the motivation of people to fight for radical life extension, for immortality. So, if you happen to know some artists, tell them about tranhumanist ideas and about the urgent need of new art that will help defeat death.

2. We learned that one of the main problems in promoting tranhumanism is belief is afterlife. Death is not for real for a religious person; they think that something better awaits them after death. Maybe they don’t pay much attention to the details of the afterlife, but the lack of doubt about it leads to refusing any effort towards life extension. Therefore, you can’t ingratiate with religion, because by doing so you add fuel to the flames of belief that immortality already exists.

We oppose merging of tranhumanism and religious ideas, the examples of which are Raelian movement, transcendent transhumanists, Mormon transhumanists, Global Future 2045 and many other irrational forms of world-views that seek to join a new powerful idea.

3. If tranhumanist ideas are described in a simple way, like let’s extend longevity, it’s good thing and let there be more science, then it sounds apocryphal and doesn’t galvanize anyone into action. Details are the things that can pesuade people. But if the ideas are described with a lot of details, then people just don’t have enough knowledge to understand what those ideas are about.

For example, biology background is needed to truly understand the possibility to extend lifespan using genetic regulation. That’s why we advocate development of courses in transhumanism and biology of aging.

If anyone is interested in this task, let’s create some transhumanist tests together. They can be about molecular biology, game theory, neurophysiology, etc.

4. People don’t like propaganda, but they readily execute direct orders about what they need to do. For example, the call to realize the importance of fighting aging doesn’t meet any understanding, but the offer to take the 23andme test will receive agreement with much higher probability.

People gladly join Longevity Party. I would love to see like-minded people in the Longevity Party project, primarily in California and Norway.

5. We noticed that the situation changes after rebranding, for example, when stem cells were renamed regenerative medicine, gene therapy – synthetic biology and fighting aging – personalized medicine.

This means that it’s a good idea to launch many different names. For example, instead of life extension – life preservation. I think that it makes sense to launch various tranhumanist projects even with a low probability of success, simply counting on that some meme may become very effective.

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