New mechanism of aging was discovered

New discovery of scientists from Harvard Medical school offers a promising approach to combat aging in muscles.  Dr. Comes and colleagues revealed the mechanisms of mitochondrial aging:  

"Ever since eukaryotes subsumed the bacterial ancestor of mitochondria, the nuclear and mitochondrial genomes have had to closely coordinate their activities, as each encode different subunits of the oxidative phosphorylation (OXPHOS) system. Mitochondrial dysfunction is a hallmark of aging, but its causes are debated. We show that, during aging, there is a specific loss of mitochondrial, but not nuclear, encoded OXPHOS subunits. We trace the cause to an alternate PGC-1α/β-independent pathway of nuclear-mitochondrial communication that is induced by a decline in nuclear NAD⁺ and the accumulation of HIF-1α under normoxic conditions, with parallels to Warburg reprogramming. Deleting SIRT1 accelerates this process, whereas raising NAD⁺ levels in old mice restores mitochondrial function to that of a young mouse in a SIRT1-dependent manner. Thus, a pseudohypoxic state that disrupts PGC-1α/β-independent nuclear-mitochondrial communication contributes to the decline in mitochondrial function with age, a process that is apparently reversible."

The scientist also conducted an experiment on rats during which they supplied the animals with NAD. The results were absolutely amazing: one week treatment lead to reverse of biological age of the rats' muscles from 24 months to 6 months. It is the same if muscles of 60 years old men become as young as muscles of 20 years old person!!!

Just amazing! I am waiting for clinical studies of this approach!

Source: CELL

BioPen

The process of aging leads to not only cardio-vascular problems, which are the main causes of dearth, but also to osteoporosis and other bone diseases, which can cause disability.

Now even if you have bone degeneration, doctors will be able to repair the bones by wonderful new device called BioPen. The BioPen, developed by researchers from the UOW-headquartered Australian Research Council Centre of Excellence for Electromaterials Science (ACES), will give surgeons greater control over where the materials are deposited while also reducing the time the patient is in surgery by delivering live cells and growth factors directly to the site of injury, accelerating the regeneration of functional bone and cartilage.

The BioPen works similar to 3D printing methods by delivering cell material inside a biopolymer such as alginate, a seaweed extract, protected by a second, outer layer of gel material. The two layers of gel are combined in the pen head as it is extruded onto the bone surface and the surgeon ‘draws’ with the ink to fill in the damaged bone section.

Once the cells are ‘drawn’ onto the surgery site they will multiply, become differentiated into nerve cells, muscle cells or bone cells and will eventually turn from individual cells into a thriving community of cells in the form of a functioning a tissue, such as nerves, or a muscle.

Source: University of Wollongong

Congratulations!

My sincere congratulations to my colleague and exPI, Alex Zhavoronkov, with getting a professorship from my alma mater MIPT.

Alex is an excellent scientists and mentor. He is doing the great work to popularize science and to help young talented students to develop their skills and find a good place in the science. Congratulations once again and good luck in the future work!

Personalized science

The problem of medical care quality is important for a lot of countries all over the world. Despite the increase in the number of technical breakthroughs and in the professionalism among the doctors, there is clearly a lack of the individual approach to patient care. No two patients are the same. Not even the identical twins. Thus it is very natural to personalize a treatment of the patient. Unfortunately, for most of the people it is too expensive to have personal doctor. However, for the wealthiest one there is a possibility to have not only personal doctors, but personal medical scientists that would not only toil on patient’s own problems, but also look for ways to prevent or entirely eradicate certain diseases.

In the article "From Personalized Medicine to Personalized Science: uniting science and medicine for patient-driven, goal-oriented research" Dr. Cantor and Dr. Zhavoronkov described a unique concept of personalized science, which could help the wealthy or skilled patients, but whole scientific community to develop and become better. The idea based on patient-doctors-scientists interactions and on rational usage each sides' talents. Briefly, the patient provides a research grant for universities or doctors-scientists team conducting a research aimed at healing the patient. The patient also supervises the work of the team and this, according to authors, is one of the keys to success. All sides benefit from this interaction: research organizations get funding, scientists and doctors get the material for study, in most cases unique, and the patient get the effective treatment.

However, I can’t help, but point out the advantage of the technique, which authors missed in the paper. Although the application of personalized science may seem to be limited by the miniscule number of wealthy patients that not only truly care about their health, but also want to advance scientific research. As prestige of the scientists is directly correlated with the number of published scientific papers, each such interaction will result in papers, available to the whole scientific community all over the world. Thus, other scientists and medical doctors could use the results in the treatment of their patients and personalized science will not only help one individual, but immensely contribute to the society.

Read article here.

Biomedical Progress Rates as New Parameters for Models of Economic Growth in Developed Countries

I would like to introduce you my new article:" Biomedical Progress Rates as New Parameters for Models of Economic Growth in Developed Countries".

In this paper me and my colleague, Alex Zhavoronkov, discussed new model of economic growth. Based on statistical data from recent decades, we assumed that the economy of the developed countries will be affected by increased eldery to young people ratio, and this even could cause a crisis.

You can find full free text article here.

Abstract:

While the doubling of life expectancy in developed countries during the 20th century can be attributed mostly to decreases in child mortality, the trillions of dollars spent on biomedical research by governments, foundations and corporations over the past sixty years are also yielding longevity dividends in both working and retired population. Biomedical progress will likely increase the healthy productive lifespan and the number of years of government support in the old age. In this paper we introduce several new parameters that can be applied to established models of economic growth: the biomedical progress rate, the rate of clinical adoption and the rate of change in retirement age. The biomedical progress rate is comprised of the rejuvenation rate (extending the productive lifespan) and the non-rejuvenating rate (extending the lifespan beyond the age at which the net contribution to the economy becomes negative). While staying within the neoclassical economics framework and extending the overlapping generations (OLG) growth model and assumptions from the life cycle theory of saving behavior, we provide an example of the relations between these new parameters in the context of demographics, labor, households and the firm.

Big step up!

I love very much my (ex)Intitute, Moscow Institute of Physics and Technology. However, there are some points in MIPT's policy, which should be improved.

I think, that one of the most importatant such points is an internalization. In MIPT courses are offered only in Russian, and that prevents international student apply to the Institute. But a big step up was made recently! Courses of MIPT appeared at Coursera! Now MIPT is one step closer to top 100 best universities of the world.

MIPT at Coursera

Why We Should Look Forward To Living To 120 And Beyond?

I am doing ageing research and happy about it, but a lot of my friends ask me:"Why are you doing this?". I have a lot of personal reasons, for example, because I am in love with my life or I do not want to look like wrinkled pea and to be disabled. However, sometimes it is now enough to persuade people to do ageing research or give money to support science.

Now, thanks to article by  Dr.Alex Zhavoronkov in Forbes I know even more reasons, why governments of all countries should pay greater attention to ageing research.  

According to the article, 

" There are clear benefits, then, in proactively stretching your expected life horizon to a number much greater than your can currently imagine. It will probably not only make you look and feel younger, but also induce the behavioral patterns of someone more youthful, enabling you to interact with younger and older people without barriers and remain productive longer than your peers.

Another benefit of setting the bar toward 120, 150 or beyond is minimizing financial risk. This will most certainly lead more of us to postpone retirement and set a course for continuous improvement, lifelong learning and active career planning.

There is definitely no harm in stretching your “ageometer” to 150. Most likely technology will catch up and exceed your expectations. The worst that can happen is you will die earlier feeling much younger than you ever thought you would. "

I high recommend you to read this article!

Why we should look forward to living to 120 and beyond? 

Image by thinkstock

A group of my colleagues proposed novel ways to prevent and combat the age-related mineralization of the connective tissue

My friends and colleagues, Anastasia Shyndyapina, Garik V Mkrtchyan, Tatiana Gneteeva (www.sceince.com), Sveatoslav Buiucli, Alexander Aliper, Alexander Zhavoronkov together with the Canadian scientists M Kulka, B Tancowny just got their paper accepted in Rejuvenation Research, a leading journal in biogerontology.

Mineralization is a very important problem in aging and I would like you to take a look at their press release below. By the way, I am also part of the FOIRMYS initiative and spent a year in two of their group projects focusing on other aspects of aging research.

The press release: 

When you open a 70-year old patient on the operating table and touch the aorta, the feeling may resemble touching an eggshell or sand paper. It is stiffer than the heart of a young person and the key reasons for this are the abundant calcium deposits in the connective tissue that accumulate with age.

The many factors leading to mineralization of the connective tissue include genetic and acquired diseases, inflammation, reactive oxygen species, but the major problem is that it occurs spontaneously during aging as calcium-containing molecules are trapped in the extracellular matrix and develop into apatite over time.

Despite its relative significance, compared to the many other areas of aging research, mineralization of the connective tissue is rarely mentioned in scientific publications and few teams are working on preventing or clearing out the extracellular aggregates.  To address the problem, a multidisciplinary team of physicians, bioinformatitians, biochemists and physicists performed a comprehensive bioinformatics analysis of the many factors involved in mineralization, identified key molecular targets and proposed a list of possible drugs to address the issue.

The results of the study were accepted for publication by a high-impact journal in biogerontology “Rejuvenation Research” and will be published shortly and can be cited as “Mineralization of the connective tissue: a complex molecular process leading to age-related loss of function”, Anastasia Shindyapina, Garik V Mkrtchyan, Tatiana Gneteeva, Sveatoslav Buiucli, M Kulka, B Tancowny, Alexander Aliper, Alexander Zhavoronkov, Rejuvenation Research, ahead of print. doi:10.1089/rej.2013.1475, http://online.liebertpub.com/doi/abs/10.1089/rej.2013.1475 , PMID 23902273

Anastasia Shindyapina together with her collaborators presented the results of the study on the 5^th of September at the SENS6 conference in Cambridge, UK.

“Aging inevitably leads to the loss of function on many levels. Mineralization of the connective tissue is one of the causes and consequences of aging and is a complex multifactorial process. Metabolic activity, diseases and external stress factors may cause calcification, but most importantly, it occurs spontaneously. Our goal is to identify least toxic ways to both prevent calcification and to repair the accumulated  aggregates.”, said Anastasia Shindyapina, ASUS Fellow for Bioinformatics and Medical Information Technology, PhD-candidate at the Moscow State University and researcher at FOIRMYS.

"Mineralization of connective tissue with age is one of the many aspects of aging that are examples of "accumulation of eventually pathogenic extracellular material", an issue that attracts too little attention within the academic community. The accumulation of advanced glycation endproducts (AGEs) and of mineral deposits both result in increased stiffness of connective tissue, impair homeostasis and contribute to a broad range of age-related diseases. Through comprehensive bioinformatic analysis of the many molecular processes involved in mineralization, Zhavoronkov's team has identified possible molecular interventions. Additionally they proposed that mineralization and AGEs work in concert and should be addressed concurrently. Anastasia Shyndyapina, the lead author on the paper, recently presented this work at the SENS6 conference in Cambridge.", commented Dr. Aubrey de Grey, Chief Science Officer of SENS Research Foundation and International Adjunct Professor at the Moscow Institute of Physics and Technology (MIPT).

About FOIRMYS

The First Open Institute for Regenerative Medicine for Young Scientists (FOIRMYS) is a non-profit volunteer initiative bringing together over a thousand enthusiast young scientists and physicians interested in regenerative medicine. It was first organized by Alex Zhavoronkov, PhD in collaboration with Sergey Yakovenko, PhD, Sergey Roumiantsev, PhD and Oleg Korzinov in Moscow with support from Anna Chapman.

FOIRMYS provides regular weekly lectures by the top academic and industry thought leaders, investors and regulators. The list of presenters includes Paolo Macchiarini (Karolinska Institute), Alexey Aravin (Caltech), Charles Cantor (Boston U, ex-director of the Human Genome Project), Augustinus Bader (Leipzig University), top managers from Beijing Genomics Institute, Malaysian Genome Resource Center, Indigo Capital Partners and many others. As part of the curriculum students participate in practicums at “Altravita IVF, FRCCPH, FORCC, Quantum Pharmaceuticals, Biopharmcluster “Northern” and Moscow Institute of Physics and Technology.

Members work in small teams comprised of scientists and physicians on ambitious outlier projects in aging and regenerative medicine with topics ranging from mineralization of connective tissue, HGPS and regulation of endometriosis to industry overviews and healthcare economics. The projects are coordinated in a crowdsourced environment and rely heavily on popular tools like Facebook, Dropbox and Google Apps. FOIRMYS developed a concept called “Personalized Medicine”, where projects are centered around the problems of a single patient, who provides samples and helps coordinate the project. Members also learn how to promote their work, create personal science blogs (including Women in Science initiative) and engage in industry outreach.

Participation in practical group projects resulted in success stories including young scientists’ publications in peer-reviewed journals, fellowships, participation in international conferences, gainful employment of young scientists and international collaborations.

SENS6 report

Hi everyone!

Recently the famous aging conference, SENS6, took place at Cambridge. Unfortunately,I could not attend it, but my friends and colleagues, Yana Aznaurova and Anastasia Shindyapina were happy to took part in it and to share their impressions.

Anastasia Shindyapina was the youngest speaker in this conference, and gave a talk about the bioinformatic analysis of factors involved in age-related mineralization of soft tissues. I think this is a topic worth to study and Anastasia and her team made greate work.

Also, one more speaker from our First Open Institute for Regenerative Medicine for Young Scientists. This was Alex Zhavoronkov, one of the co-founders of the Institute. He introduced our economic work called "New economic arguments for accelerating aging research". Although general public might not understand all formulas, but speech was great and the audience liked it.

I hope I can attend SENS7 next year=)

Prion-Like Proteins Drive Several Diseases of Aging

Mathias Jucker and Lary Walker outline the emerging concept that many of the brain diseases associated with aging, such as Alzheimer's and Parkinson's, are caused by specific proteins that misfold and aggregate into harmful seeds. These seeds behave very much like the pathogenic agents known as prions, which cause mad cow disease, chronic wasting disease in deer, scrapie in sheep, and Creutzfeldt-Jakob disease in humans.

Unlike prion diseases, which can be infectious, Alzheimer's, Parkinson's, and other neurodegenerative diseases can not be passed from person to person under normal circumstances. Once all of these diseases take hold in the brain, however, it is increasingly apparent that the clumps of misfolded proteins spread throughout the nervous system and disrupt its function.

The authors were the first to show that a protein that is involved in Alzheimer's disease -- known as amyloid-beta -- forms prion-like seeds that stimulate the aggregation of other amyloid-beta molecules in senile plaques and in brain blood vessels. Since then, a growing number of laboratories worldwide have discovered that proteins linked to other neurodegenerative disorders also share key features with prions.

Age-related neurodegenerative disorders remain stubbornly resistant to the discovery of effective treatments. Jucker and Walker propose that the concept of pathogenic protein seeding not only could focus research strategies for these seemingly unrelated diseases, but it also suggests that therapeutic approaches designed to thwart prion-like seeds early in the disease process could eventually delay or even prevent the diseases.

Sourse: Nature

Children with Disease of Never Aging May Offer Clues to Immortality

Unfortunatelly, science now  remain very far from interventions that can eliminate the aging process.

A story has recently entered the news about a rare disorder in which children don’t appear to age.  The punchline of this story is perhaps this disease holds the clue to immortality (or close to it). An eight year old girl in Montana named Debbie is said to have not aged since birth.  She weighs about 12 pounds and has only recently moved into the 3-6 months clothes size.  Her condition is so rare it isn’t yet named.

There are a handful of other people like her in the world including a 29 year old Florida man who appears to be 10 years old.Researchers don’t know what genetic flaw or mutation is severely slowing the aging process in these individuals, but unfortunately it also makes them deaf and mute.The scientist studying them believes it might be possible to find the genetic switch that is stopping aging and to one day turn it on (or off) in normal adults.It certainly makes the most sense that aging is evolutionarily and thus genetically determined. 

The secret of salamander's regeneration is opened.

Salamanders are unique among animals in their ability to regenerate lost or damaged parts. Adult salamanders can regrow heart, brain, muscles and even whole limbs. Researchers have discovered a certain type of immune cell is responsible for this fascinating ability.

Normally immune cells called macrophages migrate from the bloodstream to the site of injury in all animals from salamanders to human. In humans they are responsible or ingesting and thereby removing debris. When humans are injured the result is usually fibrotic scar tissue, limbs and most organs cannot regenerate. The researchers hoped to dissect the regeneration response in salamanders and use the learnings to apply to human regenerative medicine.In the experiment, salamanders were treated to remove their macrophages, and then underwent amputation.  Without macrophages the animals  could not longer regenerate tissue, proving these cells were responsible for the effect.

The authors reasoned the macrophages must release specialized chemical signals that allow regeneration. It is likely that the early arrival of macrophages into the regenerating axolotl blastema by 24 h after amputation, along with simultaneous induction of inflammatory and anti-inflammatory cytokines, is part of a distinct regenerative program.

Understanding the early regulation of expression patterns and timing of various extracellular matrix components by macrophage signaling is critical in identifying pathways permissive for appendage regeneration. Their early engagement in the secretion of anti-inflammatory cytokines and other factors promoting the efficient regeneration of axolotl limbs point to potential therapeutic strategies for preventing fibrotic scarring and promoting tissue regeneration in mammals following tissue injury.

Souse: PNAS

SENS6

The world's leading series of conferences dedicated to the prevention and treatment of the diseases of aging using regenerative medicine will hold its next installment later this year. The conference, entitled "SENS6: Reimagine Aging," will be held from September 3-7, 2013 at Queens' College, Cambridge, UK. As part of the biennial SENS conference series, SENS6 will be presented SENS Research Foundation (SRF), a biomedical research charity.

"What makes the SENS conferences different is the way they unite experts on every major aspect of aging," said Dr. Aubrey de Grey, SRF's Chief Science Officer. "These conferences are a place where we talk about solutions: repairing the damage that underlies each of these diseases. You won't find that comprehensive, practical approach discussed anywhere else - though, of course, we're doing our best to change that."

Topics covered at the conference will include heart disease, cancer, cellular senescence, age-relateddysfunction of lysosomes and mitochondria , and advances in gene delivery. "Based on how far we've already come, as this meeting will show, I'm extremely optimistic about the progress that the scientific community will make in all of these areas in the coming decades," added Dr. de Grey.

My friend and colleague Anastasia Shindyapina will participate in this conference. Good luck!

Sourse: SENS

New heart

Nature is giving another burst of hope to the future of organ transplants. For the very first time, a research team has been able to grow human heart tissue that beats totally autonomously. The tissue itself came from induced pluripotent stem cells (iPSCs), which started as mature human skin cells and effectively “reprogrammed” back to an embryonic state and then coaxed into becoming the desired cell, in this case those with the potential to become heart tissue or multipotential cardiovascular progenitor (MCP) cells. 

Then using a decellularised mouse heart (which is basically exactly what it sounds like — a mouse heart stripped of all its cells, leaving behind a heart framework or “scaffold”), the researchers repopulated the heart scaffold with the MCP cells. After several weeks, not only had the mouse’s heart been fully rebuilt with the human cells, it was also beating again entirely on its own at a rate of 40 to 50 beats per minute. While this is certainly an incredible achievement the heart still isn’t quite at the level of effectively being able to pump blood throughout a human body — the average resting human heart rate is 60 to 100 beats per minute.Still, with one person dying of heart disease every 34 seconds, this is more than enough cause for celebration. And we have every reason to believe that, one day in the not too distant future, repairing a severely damaged heart could be as easy as taking a simple skin biopsy and regrowing one of your very own.

Sourse: Nature

Eat less or take one pill?

Scientists who gave tablets containing purified resveratrol to obese men found it had some metabolic effects similar to those from exercise and caloric restriction, including lowering blood pressure and blood sugar levels. Research in animals over the past decade has suggested the compound can slow the development of age-related diseases and increase lifespan. 

Researches gave 11 obese men either a daily 150mg resveratrol supplement or a placebo for 30 days. Four weeks later, the two groups swapped over so that those who took the supplements first time around were given placebos and vice versa.

Regular measurements showed resveratrol lowered blood sugar levels and improved insulin sensitivity, as well as cutting triglycerides – fats found in the blood that can increase heart disease risk. Resveratrol also reduced both sleeping and resting metabolic rate and cut blood pressure.

Previous research has shown that calorie restriction can extend lifespan in laboratory animals. Some studies suggest it also offers protection from diseases such as cardiovascular disease and type II diabetis, though this remains controversial. Calorie restriction works in a similar way to resveratrol, by triggering the production of a protein called SIRT1 which improves metabolic function and keeps cells healthy in the face of stress.Muscle biopsies carried out by Prof Schrauwen's team confirmed that participants taking resveratrol saw increased SIRT1 levels. They also strongly suggested the beneficial effects on metabolism were associated with improved functioning of mitochondria, the energy factories within cells.

Sourse: Cell Metabolism

Do you want to know how many years left do you have?

The device, which has been created to encourage users to stay healthy, uses laser beams to analyse crucial cells lining blood vessels under the skin.These tiny endothelial cells are a key indicator of a person’s health, and the device’s inventors say that by monitoring them they can identify those who are ageing more quickly than normal.  The analysis of the endothelium –  the layer of endothelial cells in tiny blood vessels called capillaries – could also suggest whether someone has  cancer or dementia.Everything that goes on in your  cardiovascular system, whether you are going to have a stroke or heart attack, starts off as something going wrong in the endothelium.But once the test has been refined, they claim it should eventually be possible to tell a person how many years they have left.In tests on 220 healthy people, it was clear that some had aged more quickly or slowly than expected.  Having created a bulky experimental device, the inventors are designing a smaller prototype that can be worn on the wrist.

But there will be concerns that while some will alter their lifestyle to stay in optimum condition, others may take a fatalistic approach. Also insurance and pension companies could also use the information to alter premiums and payouts. Without any doubt, such discovery could affect not only life style of people, but global economy too.

Sourse: Lancaster University

Do you want to measure you biological age?

Measurements of some of the mediators or causes of aging are often used to determine your age, as more active aging usually implies an older biological age. For example, measures of oxidative stress, inflammation, glycation, stress or hormone levels are all important determinants of many age-related changes and are consequently used by some practitioners as a means to say that you are older or younger than your chronological age.

1) Measure your blood pressure.Blood pressure levels have a number of characteristics that make them suited to be a biomarker of aging. In particular, the systolic blood pressure which is the highest pressure achieved by the beating heart, generally increases as we get older, due to the increasing stiffness of blood vessels.

2) Control your cholesterol level. Levels of bad cholesterol (contained in low density lipoprotein (LDL) particles) rise as we get older and the higher your LDL cholesterol levels, the higher your risk of heart attacks, strokes and other diseases of the blood vessels that shorten life expectancy. Equally levels of good cholesterol, contained in high density lipoprotein (HDL) particles are used as a marker of the ability of the body to remove bad cholesterol from the walls of blood vessels, and put it back into more safer storage sights (reverse cholesterol transport). The higher your HDL cholesterol the higher your capacity to reduce the effects of bad cholesterol, particularly with regards to the development and progression of heart disease, so that individuals with high levels of HDL cholesterol have lower risk of heart disease and strokes and greater longevity.

3)  Mesure your body mass index. Body composition is a key determinant of health, disease and disability. Your body changes significantly as you get older and some of these changes can be used to track the process of aging.

4) Body composition is a key determinant of health, disease and disability. Your body changes significantly as you get older and some of these changes can be used to track the process of aging.

5) Deficiencies or relative deficiencies of hormones give established symptom complexes and should be treated. Those doctors who subscribe to the neuro-endocrine theory of aging believe that in part at least, you age because your hormone levels drop. The hormones DHEA and IGF1 (the primary metabolite of Growth Hormone) have both been suggested as the most accessible stand-alone biomarkers we have. Also you should check Testosterone / Free Testosterone, DHEAs, TSH T3 T4 (Thyroid Function), Oestrogen, Progesterone, FSH.