Tag Archives: aging research

Do Model Animals Tell Us Anything about Human Aging?

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I wrote a tiny report on the pluses and minuses of using model  animals in aging research.

Using model animals in gerontological studies has yielded an enormous wealth of useful information about the mechanisms of human aging and longevity. Animal models were crucial in identifying the conserved pathways that regulate human aging. Model organisms are fundamental for aging research, because there are serious limitations of using human subjects, such as the length of lifespan, genetic heterogeneity and vast differences in environmental influences. The shape of survival curves represents the health of the organism over time. Model organisms display significantly different lifespans, however the survival curves resemble those of humans quite remarkably. Despite this general similarity in the way we describe aging between humans and model animals, there are some distinct differences (Mitchell, Scheibye-Knudsen, Longo, & de Cabo, 2015). For instance, increasing Sir2 gene expression in yeast (Kaeberlein, McVey, & Guarente, 1999), nematodes (Tissenbaum & Guarente, 2001), and flies (Rogina & Helfand, 2004) boosts animal longevity. A small molecule called resveratrol was found to activate Sir2 and its mammalian ortholog SIRT1 (Howitz et al., 2003). Resveratrol extends lifespan of mice fed a high-fat diet (Baur et al., 2006), however it failed to have a beneficial longevity effect in mice on a standard diet (Pearson et al., 2008). This example highlights the fact that we cannot simply transfer the results of longevity interventions to humans and expect the same efficacy as in invertebrate models.

Everyday the researchers are broadening the understanding of human biology of aging with the help of various model systems. Each of them has its advantages and drawbacks. Let’s take a look at what those are for the most widely used animal models.

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Longevity Gene Therapy – Updated Projects

While discussing the longevity gene therapy project we encountered various questions and observations that prompted us to broaden the project and slightly change it. Generally, all the comments can be reduced into 5 main points:

  1. You need to enlarge the list of therapeutic genes by adding to it this and that.
  2. You want to use too many genes; therefore you need to make the project simpler by keeping only the most effective genes
  3. If you apply all the genes at the same time, some of them may cancel out the effects of other genes.
  4. Will it be safe to use viral vectors to deliver genetic constructs?
  5. How safe are therapeutic genes for the body?

Some of the observations were of completely opposite nature, so we decided to do 2 versions of the project. One of them is for aging geneticists. In it we almost double the list of the genes extending lifespan. This project will allow testing many poorly studied genes, but promising in terms of aging. Besides, some unexpected results can be obtained, which is always valuable.

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Hollywood Must Turn Its Head to Personalized Longevity Science instead of Anti-Aging Pseudoremedies

This attention-worthy article in The Hollywood Reporter signals that Hollywood people are ready and willing to do something about their longevity. The article mentions hormone replacement therapy, different check-ups and other things available in California, however completely misses 99% of what actually can be done about aging – science. Why doesn’t the author talk about the work done at the Buck Institute for Research on Aging, USC, UCLA and Stanford University?

People are looking for a ready solution, something that they can do today, and mistakenly dismiss science completely, because they think it is too far away for being applied to them. Well, this is a wrong approach. Science can be applied to a particular person’s health. It is called personalized science. It means that we can treat a given person’s health as a scientific task. There already are several examples for personalized science in action.

Martine Rothblatt created a pharma company to invent a cure for her daughter Jenesis’s rare disease primary pulmonary hypertension, she hired the best researcher in that area back in 1996 and they created the pill that significantly improved the well-being of these patients including her daughter. This venture turned out to be quite profitable as well as being life-saving.

The other example is Michael Snyder and his recent attempt to analyze “omits” data about himself. Dr. Snyder is the Head of Genetics Department at Stanford University. He was measuring 40,000 parameters and by analyzing all this health data, his team managed to spot the onset of type 2 diabetes way earlier than he would have noticed it using conventional methods.

So, there is so much that can be done using scientific approach to health. It is not cheap, and at this point of time this kind of personalized science is for the wealthy, however the Hollywood Reporter article is exactly for this kind of crowd, it describes quite expensive health services that don’t necessarily yield results. I believe the message that science is a very powerful tool to increase longevity has to be brought to the general public, especially here in California where a great number of outstanding aging research facilities are situated.

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Biology and Biology of Aging Resources

We have prepared a list of resources that can help understand biology of aging. We tried to find easy to grasp information sources and compiled a list of lectures, audio courses, popular science books and articles on biology in general and biology of aging in particular. The selected resources probably don’t exhaust the whole picture of aging science, but they shed light on the main ideas and research directions in this area.

For those who have never studied biology systematically, we suggest to take a look at the MIT “Introduction to Biology” course.

These lectures are mainly about different aspects of molecular biology, biochemistry anad genetics. Beside that, the course provides understanding how this knowledge can be applied in real life: in gene engineering and molecular medicine.

A good online course «Useful genetics» from Coursera.org addresses genetics and its applications.

One of the lectures from this course is by the way about genetics of aging.

“Frontiers in biomedical engineering” course was presented at Yale University and is available on Youtube.

Additionally you can listen to the audio course on molecular and cell biology from UC Berkeley.

Now let’s talk about biology of aging. For starters you can read a popular science article in National Geographic titled «Longevity». It provides the most general knowledge about the genetic mechanisms that regulate aging. A very detailed description of aging on various levels (from molecular to whole organism) is provided in the books «Biology of Aging» by Roger B. McDonald and «Biology of Aging: Observations and Principles» by Robert Arking. There was a couse at MIT on biology of aging, age-related diseases and potential therapies, “The Biology of Aging: Age-Related Diseases and Interventions”, the website provides the summary. The topics that are mentioned in this course generally depict the main research avenues in biology of aging and the can be used as reference points for self studying.

Moreover, we have put together a list of lectures given by prominent scientists that provide a look at aging from different perspectives. The lecture by Vadim Gladyshev is devoted to the topic of various theories of aging – “Molecular Cause of Aging”.

Noteworthy are the lectured by the leading scientists from Stanford University, Thomas Rando and Anne Brunet  -“Longevity and Aging in Humans”

and by Janko Nikolich-Zugich from Arizona State University – “The Biology of Aging: Why Our Bodies Grow Old”

Nir Barzilai, Director of Aging Research Institute at Albert Einstein College of Medicine gave a lecture on genes, facilitating longevity in humans – “The role of protective genes in the exceptional longevity of humans” by Nir Barzilai .

Konstantin Khrapko talks about the role of mitochondia in aging – “Mitochondrial Genetics of Aging”.

Judy Campisi, professor at the Buck Institute for Research onaging, gave a talk on the relationship of cancer and cell senescence – “Cancer and aging: Rival demons”

Additionally, several lectures are about the aging of the brain – “The Aging Brain: Learning, Memory, and Wisdom,” by John Gabrieli.

and «The Aging of the Brain» by Carol A. Barnes

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We Created the Longevity Party

We made the first step towards the creation of the Longevity Party. On July, 19 the initiative group of 10 people gathered together in Moscow to establish the first political party aimed at extending human lifespan using technological advances. Among these 10 people were Mikhail Batin, Alexey Turchin, Leonid Kaganov and Elena Milova. This is the very first step in the long and hard process of legally registering a political party. I believe this is one of the most important things that happened in the past few years in fighting aging. Nowhere in the world never before people expressed their desire to life longer in a form of a political movement.

The main goal of the Longevity Party is to increase human lifespan so that people could live for as long as they would like to and remain young and healthy. We would like to achieve this goal by promoting scientific research and technological advances in regenerative medicine, genetics of aging and longevity, neuroscience, computer modeling of biological processes and other areas of life extension. Longevity Party is 100% transhumanist party.

There are so many things that we need to do in order to legally register the Party, and we have already started doing them. I will be posting the updates as frequently as possible. Next big thing we need to finalize is the Program of the Party. Then we have to have at least 2 people in 42 regions of Russia as representatives of the Party and have the founding meeting after which the Party can be registered and eventually appear in the voting ballots.

Our goal is to influence the authorities to support life extension technologies and increase funding for research aimed at improving people’s health and extending longevity.

Join us. Together we will win. Longevity Party must be a global initiative.

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Melanie Swan: A summary of important themes in aging research

Melanie Swan, MBA, is an Affiliate Scholar of the IEET – The Institute for Ethics and Emerging Technologies. Ms. Swan is a science generalist, hedge fund manager, and founder of citizen science organization DIYgenomics. She serves as a researcher and advisor to foundations, government agencies, corporations, and startups, and is active in the community promoting science and technology. Her life mission is to impact millions of people by facilitating the widespread deployment of beneficial high-impact science and technology.

Melanie recently summarized some important themes in aging research that were discussed at the second Bay Area Aging Meeting:

Processes work in younger organisms but not in older organisms

A common theme in aging is that processes function well in the first half of an organism’s life, then break-down in the second half, particularly the last 20% of the lifespan. In one example, visualizations and animations were created from the 3D tissue-sectioning of the intestine of young (4 days old) and old (20 days old) C. elegans. In the younger worms, nuclei and cells were homogenous and regularly spaced over the course of the intestine running down the length of the worm. In older worms, nuclei disappeared (an initial 30 sometimes ultimately dropped to 10), and the intestine became twisted and alternately shrunken and convoluted due to DNA accumulation and bacterial build-up.

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The main question in Biogerontology

mechanisms of aging, white-footed mouse, lab mouse, mice, aging, fight aging, aging research, biogerontology, funding, stress resistance, oxidative stress, George Sacher, long-lived animals, negligible senescence, naked mole rat
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.

mechanisms of aging, white-footed mouse, lab mouse, mice, aging, fight aging, aging research, biogerontology, funding, stress resistance, oxidative stress, George Sacher, long-lived animals, negligible senescence, naked mole rat
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?

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