February 2011

UK Charity BGRF Funds A Major New Study Into Haematopoietic Stem Cell Transplantation And Cancer

BGRF, a UK charity is funding a major study investigating the therapeutic potential of transplanting Haematopoietic stem cells to evaluate how they can affect the aging process specifically in relation to the increasing risk of cancer with age.

Feb 25, 2011 – The Biogerontology Research Foundation (BGRF) is a UK registered charity which is committed to the support of aging research in order to address the challenges of a rapidly aging population and to reduce the impact of disease on future generations. BGRF are in the second year of funding an ambitious project in which researchers from the Max Planck Partner Group Program on Stem Cell and Aging Research in Beijing and Ulm (Germany) are investigating the therapeutic potential of transplanting Haematopoietic (blood) stem cells into mice. This exciting project intends to evaluate the principle that stem cell transplantation could be useful in combating the aging process specifically in relation to the increasing risk of cancer with age, given an improved stem cell environment.

Cancer is probably going to be the hardest aspect of aging to defeat, because it has natural selection at its disposal. Some of the most promising approaches to combating cancer try to fight fire with fire, i.e. to use natural selection against it, by optimising the immune system’s anti-cancer potential, but even this approach has yet to show decisive results. BGRF are funding a project that seeks to put in place one key part of a radically new therapy, which tackles the evolutionary prowess of cancer head-on.

The approach consists of two parts: one involving gene therapy, the other involving stem cell therapy. The gene therapy part involve deleting the genes necessary for the elongation of telomeres (the ends of our chromosomes). Cancers cannot grow large enough to be fatal for humans without expressing such genes, so even the high mutation rate in a cancer cannot save it if these genes are missing from its DNA. However, in order to be sure that we delete these genes from every cell that could form a cancer, we have to delete them from every cell in the body that is capable of dividing – including cells that need to divide hundreds of times during life in order to maintain our bodies. Luckily, though, there are only three or four such cell types, namely the stem cells of the blood, skin, gut and possibly lung – and in each case it seems likely to be sufficient to replenish these stem cells every decade or so with new ones that initially have long telomeres. The project being funded by BGRF is investigating this stem cell replenishment process in mice, in respect of the blood.

Mice are the model organism of choice in most early-stage development of pioneering medicine, because they are easy to manipulate genetically, are relatively short-lived, and are anatomically quite similar to humans. That is true here too, though in this case the necessary manipulation is quite elaborate. First, the researchers need to use mice in whom the most important telomere-elongating genes have been removed really thoroughly, not by gene therapy but by a procedure called “knockout”, which is much simpler but cannot be done in animals that are already alive. Then, they need to alter their genes in a second way, which partially protects their gut stem cells but not their blood stem cells from the effects of telomere shortening, so that the first thing that goes seriously wrong in the mice is their blood. Finally, they have to prepare blood stem cells (“HSCs”) for transplant into these mice that can be distinguished from the recipient’s own blood by the presence of a genetic marker. BGRF have been fortunate to secure the enthusiastic interest of the world leader in this area, Prof. Lenhard Rudolph of the University of Ulm, and his long-time collaborator Dr. Zhenyu Ju of the University of Beijing. These researchers were responsible for much of the groundwork that makes this project feasible, and no one is so well placed to perform it. In previous work (prior to BGRF involvement), these researchers found that transplantation of wild type HSCs with long telomere reserves could not rescue the premature aging of late-generation telomerase-deficient mice, due to age–dependent cell-extrinsic alterations impairing stem cell engraftment and function. The current project is designed to further explore the potential therapeutic value of stem cell transplantation in age-related telomere-dependent tissue degeneration under the condition of a rejuvenated cell-extrinsic environment.

The group’s preliminary data showed that Exo-1 deletion rescued the age-dependent environmental defects in telomere dysfunctional mice, but did not improve the HSC-intrinsic defects, as tested by a competitive re-population assay. These double-knockout (Exo-1 and telomerase) mice were transplanted with wild type HSCs at various ages, and will be followed up until death. If the experiment succeeds, the results will provide proof of the principle that stem cell transplantation could be useful in combating the aging process specifically in relation to the increasing risk of cancer with age – given an improved stem cell environment.

The project has now been running for a year, and all the above tools and reagents have been successfully developed. During the remainder of the project, we will be able to use these tools to determine whether mice that are becoming anaemic due to the telomere-mediated failure of their blood stem cells can be revived by the introduction of new stem cells that are also unable to extend their telomeres but initially have long telomeres. In June 2011 Dr Zhenyu Ju will be presenting his findings on this project at the American Aging Association meeting in Raleigh, North Carolina, between the 3rd and 6th of June 2011.

August 2009

ADVANCING AGEING AND CANCER RESEARCH

Friday, August 21st, Reading, UK – The Biogerontology Research Foundation in collaboration with the Institute for Biology of Aging funds research in hematopoietic stem cell transplantation in telomerase-knockout mice.

Mammals must finely balance stimulation and suppression of cell division: over-permissive cellular proliferation promotes cancer, whereas over-restrictive cell division promotes degeneration. This is especially true in tissues with a high cell turnover, such as the blood. Genetic manipulation of the machinery that maintains the ends of our chromosomes, combined with cell therapy, is potentially a very powerful way to alleviate this problem. However, such an approach is highly complex; as a result, researchers have been reluctant to investigate its components. In this new project, the blood will be used as an example to demonstrate the feasibility of such a manipulation.

Recent data suggest that impaired function of adult stem cells could contribute to the ageing process and decline of organ maintenance and function and there is mounting evidence that accumulation of DNA damage can limit stem cell function by triggering stem cell intrinsic checkpoints. Telomere shortening represents a cell intrinsic mechanism that leads to an accumulation of DNA damage in ageing cells. First noted as a mitotic clock for cellular ageing, telomere shortening has now been documented in most organs and tissues of ageing humans.

“This project will be the first ever test of whether intrinsically mortal stem cells can maintain a proliferating tissue indefinitely if periodically replenished. If the answer is yes, this will motivate exploring such treatments as part of an exceptionally robust cancer-prevention therapy”, said Aubrey de Grey, Chief Scientific Officer of the SENS Foundation, an American charity that works to develop new therapies to treat diseases of the elderly.

Previous experimental evidence in late generation telomerase knockout mice indicates that telomere dysfunction limits the hematopoietic stem cell (HSC) function and maintenance during ageing. To test the hypothesis that transplanting HSC with long telomeres can improve survival and organ homeostasis, the BGRF and the IBA will support the work of the international research team led by Zhenyu Ju, MD, PhD^*together with Leonard Rudolph, MD^**. Over the three year period the group will conduct series of experiments transplanting the HSCs from the wild-type mice into telomere dysfunctional mice.

In addition, the research team will also investigate whether telomerase has a role in HSC function independent of its role in regulating telomere length. The group will test whether HSCs from the early- generation telomerase knockout mice can repopulate and rescue the ageing of hematopoietic system in late-generation telomerase knockout mice.

^* Zhenyu Ju, M.D. and Ph.D., Principal Investigator, Max-Planck-Partner-Group-Program on Stem Cell and Aging Research Associate Investigator, Sino-German Laboratory for Aging and Regenerative Medicine, Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China
^** K. Lenhard Rudolph, M.D., Chairman, Department of Molecular Medicine and Max-Planck-Research Group on Stem Cell Aging, Ulm, Germany

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a registered UK charity # 1124054. The BGRF seeks to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF will fund research which, building on the body of knowledge about how ageing happens, will develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce effective treatments for the diseases of ageing. The goal is to improve quality of life in the elderly. The BGRF seeks to use modern biotechnology to attack the changes that take place in ageing, and to address the fundamental mechanisms of those diseases.

About the Institute of Biology of Aging:

The IBA is a non-profit research organization established to identify, stimulate and support aging research. The IBA has supported research projects in China, Germany, Russia, UK and US. The organization offers research fellowships to outstanding scientists at top academic institutions and helps academic investigators and prospective start up companies acquire initial capital to commercialize aging research.

Digest

Digest: Scientific

Brisk Research on Potential Anti-Aging Drug

A new ‘anti-aging’ drug is being researched at the Wistar Institute, focusing on prevention of a niacin-sirtuin interaction, which could potentially lead to a treatment to significantly enhance human healthspan. Even if it does not live up to its full promise, it could still retard age-related disorders, including obesity and Type II diabetes, making it a most exciting avenue of research.

http://www.drugresearcher.com/Emerging-targets/Possible-anti-aging-drug

Weakness can be fought in elderly persons with the help of drugs

The loss of muscle mass giving rise to what is known as ‘frailty’ is one of the primary debilitating changes that come with old age, and as such a perfect area of interest for the BGRF. According to a researcher at the University of Virginia, “frailty is one of the scourges of elderly persons, and as researchers are beginning to learn about its causes, they are asking whether growth hormone deficiency is one of them,” leading in turn to research on the drug discussed in this article.

http://www.msnbc.msn.com/id/27524685/

Dementia Research

According to researchers at Gothenburg University in Sweden, some cognitive skills fade rapidly nearly 15 years before death, rather than the five years indicated by past research. Following from last month’s articles, more evidence that the symptoms of Alzheimer’s are due not to the characteristic plaques, but to the neurofibrillary tangles. In this study vitamin B3 was shown to cause improved memory retention in mice, both with and without Alzheimers disease.

http://www.msnbc.msn.com/id/26426721/
http://www.worldhealth.net/news/vitamin_b3_may_protect_against_alzheimer

A herb to reverse telomere shortening

According to biotech company Geron, their TA-65 chemical, made from the Chinese herb Astragalus, reverses the process of telomere shortening by activating telomerase. TA Sciences have translated this to a therapeutic process already, though priced out of reach of the mainstream.

http://antiagingnutritionnews.com/blog/422/anti-aging-telomere-treatment-is-here/

Treatments for brain and lung tumors

Scientists at Wake Forest University Baptist Medical Center have discovered a combination of three drugs which can be used for the treatment of brain tumors. Meanwhile researchers at the Emory University School of Medicine have discovered that when a key gene is cut off lung cancer tumor cells become less able to form colonies, and in effect die from homelessness: “Targeting this critical molecule could lead to meaningful therapeutic progress,” notes one of the researchers.

http://www.drugresearcher.com/Emerging-targets/

Medicines to mimic calorie restriction

Calorie restriction is the only proven method of significant health-span extension in mammals, so mimicking its effects could lead to therapies of huge importance to the elderly. The first article, covering research by David Sinclair and Rafael de Cabo, reviews yet more evidence that resveratrol produces just such a mimicking effect. And until available in a pill, the prefect way to consume resveratrol: wine! Resveratrol is an organic compound naturally present in grapes, and is particularly enriched in red wine. Research on consumption of resveratrol by fish was found that to slow down the aging process, according to the researchers from Lay Line Genomics, a company focused on neurodegenerative and ageing related diseases.

http://www.nhne.org/news/NewsArticlesArchive/
http://www.drugresearcher.com/Emerging-targets/

Digest

Digest: Scientific

Cancer: the end in sight?

http://www.economist.com/science/displaystory.cfm?story_id=12202589

The Economist takes an optimistic look at a hypothesis gaining much traction in recent years: that cancers grow from stem cells just as regular organs. This holds the promise of a new generation of treatments, and “if it does, it is possible that the headline-writer’s clichй, ‘a cure for cancer’, will come true over the years”

http://www.physorg.com/news140929220.html

Another possibility of that same headline-writers’ clichй, from an unusual source: long-lived, small-bodied rodents such as squirrels. With research focused so much on humans or the mouse model, this article raises the suggestion that we have overlooked an entirely new mechanism for tackling cancer, involving cell-monitoring processes, and providing cancer protection without telomerase supression.

Cancer: other developments

http://www.worldhealth.net/news/high_calcium_levels_linked_to_fatal_pros

New information on one of the big killers of old age men. Research on nearly 3000 men revealed that high levels of calcium in the blood are more likely to develop prostate cancer than their counterparts, with clear implications for the elderly male population. http://www.worldhealth.net/news/immune_system_protein_promotes_tumor_gro Meanwhile, an example of the complexity of cancer mechanisma and the surprises still uncovered by researchers. While the immune system is seen as a vital protection, researchers at the University of Pennsylvania School of Medicine have discovered an immune system protein that aggravates tumor growth.

Calorie intake, longevity and cancer are correlated

http://www.eurekalert.org/pub_releases/2008-09/uouh-lca091808.php

More insights into the genetics of cancer, once again possibly pointing the way to obtaining cancer protection along with increased life- and healthspan, this time from the Huntsman Cancer Institute. Research into worms has pointed to links between two genes: one of aging, and one of cancer. Intriguingly, their operation seems to be affected by calorie intake, so raising hopes of identifying the mechanisms of the beneficial effects of caloric restriction. And importantly, the genetics in question are close enough to humans’ to have the potential for translation into meaningful healthspan-increasing therapies.

Caloric restriction does not lead to bone loss

http://www.sciencedaily.com/releases/2008/09/080922174521.htm

Caloric restriction is the only proven way to significantly extend healthspan beyond the usual diet and exercise approaches. More evidence of the efficacy of this technique comes from the Pennington Biomedical Research Center, whose research shows that nutritious but low-calorie food leads to weight loss without affecting bone density in young adults.

Inhalers: another cause for heart attacks

http://news.bbc.co.uk/2/hi/health/7631688.stm

News on another batch of the biggest killers of old age. An article published in the Journal of American Medical Association states that patients using Inhalers are prone to increased risk of heart attack, stroke and cardiovascular diseases by around 58%.

Americans are more prone to osteoporosis

http://www.agingresearch.org/content/article/detail/2077/

The National Osteoporosis Foundation’s Dr. Joan Lappe has emphasized on the need for improved research on osteoporosis.

Pain: the cause and effect of arthritis

http://www.eurekalert.org/pub_releases/2008-09/uorm-nsp092508.php

Recent studies have revealed that pain itself is the cause of arthritis and not arthritis the cause of pain.

Digest: Economic, Political and General

What is Health?

http://www.nytimes.com/2008/09/30/health/views/30essa.html

At its heart, the BGRF aims to increase human healthspan. But just what do we mean by ‘health’? In this absorbing essay, a doctor ponders this deceptively simple question.

A never ending life – boring or interesting?

http://www.depressedmetabolism.com/2008/09/25/immortality-and-boredom/

On the outskirts of aging research lies the possibility of major extensions in life- and healthspan. But would such things be undesirable on grounds such as boredom? Aschin de Wolf reviews Bernard Williams’ proposition that this is in fact the case.

Digest

Digest: Scientific

Telomeres and cancer: biomarkers, and the suggestion of a revolutionary breakthrough

http://www.genome-technology.com/issues/blog/general/148754-1.html
http://www.mailonsunday.co.uk/health/article-1050920/Gene-tests-man-live-healthy-125-remove-threat-cancer.html
http://www.independent.co.uk/life-style/health-news/enzyme-discovery-may-hold-key-to-cancer-treatments-914754.html

University of Ulm scientists have identified biomarkers that are indicative of . The relevance and potential usefulness of this work are shown by the demonstration of an increase in these markers in people with age-related disease.

Meanwhile, a tantalizing announcement from the Spanish National Cancer Research Centre, from a team working on genetically modified mice. The researchers introduced an extra copy of three genes: one was telomerase, which helps prevent telomere shortening, and can therefore theoretically increase lifespan, but can be associated with increased cancer risk. The others were p53 and p16, and the combination of the three brought about both increased healthy lifespan, along with reduced cancer incidence. The incidence of cancer, in fact, is practically zero, while the 45% lifespan increase, in the words of the lead researcher “opens the door to [the possibility] that humans could live 125 years and without cancer.”

Taking a different tack, broad-spectrum anti-cancer therapies that target telomerase have moved a step closer as scientists have deciphered the enzyme’s active region and its atomic-level structure.

Ageing of an entire organ is stopped for the first time

http://www.worldhealth.net/news/scientists_stop_the_aging_process
http://www.genome-technology.com/issues/blog/general/148734-1.html

As we age it is difficult to get rid of damaged protein, as a result of which toxic material builds up and causes many of the disorders considered ‘age-related’. By stopping the harmful protein buildup inside the livers of mice, this aspect of ageing was halted by researchers. The long term implications of this are clear and potentially enormous. Lead researcher Ana Maria Cuervo commented that “our findings are particularly relevant for neurodegenerative disorders such as Parkinson’s and Alzheimer’s”

Cancer-related genes identifiedhttp://www.plosone.org/article/info:doi%2F10.1371%2Fjournal.pone.0003007
http://www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1000138
http://www.pnas.org/content/early/2008/08/15/0805242105.short?rss=1

A crop of other genetic discoveries around cancer, firstly that skipping of exons in encoded transcripts cause10-20% of cancer-related gene mutations. PAttern-based Correlation (PAC) is a strategy used to screen such exon-skipping. PAC has been tested on human cancer samples also.

In America, breast cancer is the second leading cause of cancer deaths in women. Cysteine-rich intestinal protein 1 (CRIP1) has now been identified for the early detection of breast cancers. Meanwhile, a study on 18 breast cancer-related genes with 340 SNPs has revealed that BRCA1 serves to provide protection against this form of cancer.

Studies into salamanders point the way to greater powers of regneration

http://www.technologyreview.com/Biotech/21265/?a=f

Scientists at the Salk Institute for Biological Studies are trying to study the axolotl salamander. It has the capacity to grow almost any part of its body which is damaged or amputated. Scientists are motivated by this amazing power of regeneration, and its potential application to humans in the longer term. On first results, many of the genes allowing this remarkable capability do have direct analogues in humans.

Prevention is better than cure?

http://www.nytimes.com/2008/08/12/health/12well.html?_r=1&oref=slogin
http://www.worldhealth.net/news/is_stroke_prevention_surgery_worth_the_r

According to recent studies the old maxim does not hold true for early detection for prostate cancer. “Cancer screening can do more harm for older people” is what is detected by the United States Preventive Services Task Force. The complex risk factors around cancer screening always pose problems, and this study would seem to have direct implications for today’s elderly population.

Similarly, another study gives warning of the dangers associated with stroke prevention surgical procedures.

New antibiotics for MRSA

http://news.bbc.co.uk/2/hi/uk_news/wales/7543930.stm

Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterium responsible for difficult-to-treat infections in humans. MRSA often claims the lives of hospital patients whose immune systems are not at full strength, and as such is of concern to the elderly population. Researchers at Swansea University are developing the antibiotic from maggot secretions from the common green bottle fly into a medicine to tackle 12 strains of MRSA, as well as E.coli and C.difficile.

Enucleated stem cells poduced in the lab

http://www.newscientist.com/article/dn14565-first-red-blood-cells-grown-in-the-lab.html ?DCMP=ILC-hmts&nsref=news5_head_dn14565

Another item not specifically age-related, but of potential benefit to the aged as well as anyone else: the first production of enucleated red blood cells grown from stem cells in the lab. Enucleated cells have expelled their nuclei, which prevents them turning cancerous, leaving them ready for transfusion.

Digest: Economic, Political and General

An Experiment in Research Funding

http://online.wsj.com/article/SB121814080611321763.html

An interesting approach to the funding of science, in part a response to the restrictiveness of US federal funding of human stem cell research, spearheaded by Alan Trounson, a pioneering Australian embryologist at the California Institute of Regenerative Medicine. Public bonds are being used for funding this research for the first time in the US. While nobody can say what therapies may result in the field of ageing, we wish Dr Trounson well in his novel approach.

Announcements

Date: 24 July 2008.The Biogerontology Research Foundation to support an aging resource at University College London

Further details in the press release.

Date: 21 July 2008. David Fisher Resigns as Trustee

With regret, BGRF co-founder David Fisher has resigned his trusteeship, as he felt current circumstances left him unable to devote sufficient attention to BGRF matters to fulfil his responsibilities as a trustee. He hopes he will be back working with us in the future, as do we.

Digest

Digest: Scientific

Nerve cell production points the way to repair aged brains

http://www.telegraph.co.uk/earth/main.jhtml?view=DETAILS&grid=&xml=/earth/2008/06/24/scibrain124.xml

Scientists at the Burnham Institute for Medical Research in La Jolla, California, have revealed that by using genetically programmed embryo cells brain repair is possible. This could be the first reliable method of producing nerve cells, with clear implications for the alleviation of age-related degeneration of the brain and nervous system.

Stems cells reprogrammed in mouse brain

http://www.sciencedaily.com/releases/2008/06/080630093621.htm

Manipulating cultured stem cells is one thing, but Researchers at the Salk Institute for Biological Studies have succeeded in reprogramming adult stem cells within a mouse brain. This research may help the treatment of neurological diseases, such as multiple sclerosis, stroke and epilepsy, that not only affect neuronal cells but also disrupt the functioning of glial support cells.

Exercise without effort for the elderly?

http://news.bbc.co.uk/1/hi/health/7535770.stm

Exercise benefits the old just as much as the young, but is often not as practical as we age. It has been recently announced that two possible pills could provide the body with the benefits of exercise, but without requiring any physical activity. Developments like this, born of ever-greater understanding of how our bodies’ cells work, could provide the practical therapies we seek to address the symptoms of aging.

Alzheimer’s latest

http://www.washingtonpost.com/wp-dyn/content/article/2008/07/18/AR2008071801614.html
http://www.abdn.ac.uk/mediareleases/alzheimers-breakthrough.shtml

The July issue of The Lancet looks at research into Alzheimer’s and finds mixed progress: one older drug, dimebon, significantly improves symptoms, while a previously-promising vaccine does not, despite complete removal of amyloid plaques. This in turn fuels the debate on whether the plaques themselves are the cause of Alzheimer’s symptoms, and whether it is even desirable to remove them. Indeed, the second article reports a massive 81% slowdown in progress of the disease, by targeting the ‘tangles’ of abnormal tau protein, rather than the plaques.

Identifying genes which protect from the diseases of aging

http://www.technologyreview.com/Biotech/21092/?a=f

A new study will sequence 100 genes in 1,000 healthy old people, to try and shed light on the genetic variations that insulate some people from the ailments of aging, including heart disease, cancer, and diabetes. The aim of this research will be to identify the molecular basis for such individuals’ health, with the future goal of mimicking these effects with drugs.

Genetics vs. wear-and-tear

http://www.independent.co.uk/

On the subject of genetics, the debate continues on whether aging is purely an accumulation of damage, or whether there are signals that instruct our cells to behave differently as they age, and whether such signals could be susceptible to genetic manipulation. In either case, the strategy of the BGRF remains unchanged, because what remains undisputed is that damage does accumulate with age, and that such damage causes suffering, but the debate remains of the greatest interest.

Longevity indicators to help tackle aging

http://longevity-science.blogspot.com

A new study attempts to correlate physiology with longevity, with the aim of estimating an individual’s potential lifespan in his youth. Key findings include the highly negative impact of obesity; and the fact that build is a better indicator than other variables such as height.

Creating induced pluripotent cells

http://www.bizjournals.com/sanjose/stories/2008/06/30/daily10.html
http://www.upi.com/Top_News/

The California Institute for Regenerative Medicine has granted $5.6 million to researchers from the Stanford University School of Medicine to support the creation of new pluripotent human stem cell lines. Meanwhile German developmental biologists have found a simpler and safer way for creating induced pluripotent stem cells. It is to be hoped that this kind of basic work lays the ground for developing stem-cell based therapies to alleviate the aliments of age.

Research on cancer vaccinations

http://www.fightaging.org/archives/001525.php

A demonstration of the variability of some forms of cancer vaccine shows that immune system cells’ capacity to identify and kill cells of a particular type of cancer varies enormously from person to person, even with medical interventions designed to point the immune system in the right direction.

Insights into the complexity of Crohn’s disese

http://www.redorbit.com/news/health/1456670/crohns_disease_linked_to_more_genetic_variations/

Genetics gives much cause for hope that we really can intervene in age-related conditions, but a recent publication into Crohn’s disease shows just how intricate the systems in question are. According to the findings, the disease could be more complex than previously thought: 32 genetic variations causing Crohn’s disease have been found by the researchers.

Digest: Economic, Political and General

Videogames for the elderly

http://discovermagazine.com/2007/may/the-elastic-brain/?searchterm=brain%20training

Although little in the way of clinical trials has been done, brain-training videogames ofer immense promise for the elderly: effectively restoring brain cells which have atrophied with age. If this approach lives up to its promises, it could be an easy route to regining decades-worth of mntal agility

Optimism on aging

http://www.dailybruin.ucla.edu/news/2008/jul/14/within-20-years-you-wont-have-grow-old/

The UCLA’s student publication the Daily Bruin carries a remarkably optimistic piece on the defeat of aging within a couple of decades, based on interventions to repair the damage of old age. Whether this really comes to pass in such a timetable or not, the BGRF is committed to help develop practical therapies as soon as possible.

Books: Mortal Coil

http://online.wsj.com/article/SB121574024132244741.html

For a view on how today’s research into practical interventions fits into the sweep of mankind’s attempts to defeat aging, David Boyd Hancock’s “Mortal Coil” chronicles this quest with “wit and learning”, according to a review in the Wall Street Journal.

Announcements

Upcoming announcement: BGRF’s first support of research

Details will follow in due course, but even though the BGRF is in its early days, we are already setting up an arrangement whereby we will be funding the support of a colony of aged mice. This will be in the spirit of supporting a common good associated with ageing research, and is a small but concrete step on our path.

Press release to follow.

Digest

Digest: Scientific

Pfizer Bets on Stem-Cell Cures

http://www.forbes.com/business/2008/06/21/pfizer-blindness-research-biz-health-cx_rl_0623stemcell.html

Pfizer, the major pharmaceutical company based in New York, is betting that a radical new adult stem-cell treatment may be able to stave off diabetes-induced retina damage, a leading cause of blindness. This is interesting for two reasons: it represents ‘Big Pharma’ investment in radical regenerative medicine of the type championed by the BGRF; and the funding route shows that people are willing to think in innovative ways on how to get regenerative medicine treatments developed.

Cancer Patient Cured by Injecting His Immune Cells

http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/06/18/scicanc118.xml

A cancer patient experirenced a full recovery following the injection of his own immune cells in a ground-breaking treatment. Although the research is in its early stages, melanoma is one of the best targets for immunotherapy and these results are highly promising. Moreover, immunotherapy is an appealing approach for many future age-related therapies, and data from studies like this will feed this field in general.

Red Wine’s Longevity Benefits Spur Research

http://www.nytimes.com/2008/06/04/health/research/04ageing.html

Further evidence of the beneficial effects of resveratol on extending healthspan. Equally interesting is the effect that such research is having on research into longeveity drugs, which may in time provide routes to the rejuvenation therapies we are ultimately seeking.

Regular Exercise Keeps Heart Disease At Bay

http://www.bbc.co.uk/health/conditions/heart/prevention_activity.shtml

“Those who think they have not time for bodily exercise will sooner or later have to find time for illness,” as Edward Stanley put it back in 1873, and this article details simple ways to enhance quality of life. This is deferment of ageing rather than rejuvenation, but the article is interesting for anyone interested in extending healthspan. More importantly, the interest here is what just exercise and similar lifestyle factors do, and whether we can in time harness those mechanisms to help people who, for instnce, cannot exercise.

Researchers Convert One Cell Type to Another

http://www.telegraph.co.uk/earth/main.jhtml?xml=/earth/2008/06/18/scistem118.xml

Bodily damage can be repaired by use of stem-cell-based “biological alchemy” as reported in the UK’s Daily Telegraph.

Ageing: Causes and Solutions

http://www.fightageing.org/archives/001503.php

Another interesting article for anyone sharing the BGRF’s outlook: a take on just what ageing is caused by, and how we could tackle each aspect in turn. Specifically, the article does not just put across the the view that ageing is due to the biochemical damage our body undergoes during our lifetime, but it lists out what the areas of damage are. The author also draws a clear distinction between ageing, as a positive process of maturation, and the negative impacts that ageing has on our bodies – a distinction we heartily share.

Interview with Aubrey de Grey

http://www.wired.com/medtech/health/news/2008/06/methuselah

Among the most optimistic of those who share the BGRF’s belief in rejeuvanation as the best approach for combating ageing is Aubrey de Grey. This article in Wired magazine covers not just de Grey’s thoughts on the subject, but also some of the other organistaions and research programmes which have a similar philosophy.

Digest: Economic, Political and General

Loss of Function in the Elderly Predicts Death

http://pub.ucsf.edu/newsservices/releases/200806241/

Loss of function may be a more accurate predictor of lifespan than disease, according to a new study. This article discusses the implications of this finding on those who evaluate heath-care and effects on heathspan

July 2008

The Biogerontology Research Foundation to support an aging resource at UCL University College London

Reading, UK – The Biogerontology Research Foundation to support an aging resource at UCL (University College London)

The study of mammalian aging in model systems in a controlled laboratory environment is essential if we are to evaluate experimental interventions designed to postpone or alleviate aging when begun late in life. Such studies are rare at present, not least because of the scarcity of suitable experimental material, yet they clearly have far more biomedical relevance and potential than interventions begun early in life or by germ-line genetic manipulation. The BGRF hopes that its support for this resource will be the first step towards elevating work on late-onset interventions in aging to the prominence that it merits within gerontology and within biology as a whole.

The UCL resource is under the expert management of Dr. Raya Al-Shawi, Senior Research Fellow and facility manager at the UCL Medical School . The BGRF is already discussing with Dr. Al-Shawi the prospects for expansion in the future as and when additional funds become available. Dr Al-Shawi said “Our interests are in understanding the processes of normal aging. The support provided by BGRF is most welcome, and in the future we hope to be able to share an expanded resource with other academics to further studies of aging”.

About the Biogerontology Research Foundation:

The Biogerontology Research Foundation is a registered UK charity # 1124054. The BGRF seeks to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF will fund research which, building on the body of knowledge about how ageing happens, will develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, which are required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of aging, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

June 2008

Biogerontology Research Foundation receives charitable status from the Charity Commission for England and Wales

Reading, UK – On Wednesday, May 14 the Biogerontology Research Foundation (BGRF) met the requirements of the Charity Commission for England and Wales and received a charitable status with the registration number 1124054.

The mission of the BGRF is to support the application of our knowledge of the mechanisms of ageing to the relief of disability, suffering and disease in old age. The formal aims of the charity are to relieve sickness and preserve, protect and advance all or any aspects of the health of elderly persons and to advance the education of the public in the field of biogerontology.

“The decision to grant the BGRF registration as a UK charity represents an important milestone in the effort to defeat the diseases of aging. It will provide us with a platform to direct resources towards drastically under-funded scientific research projects that target the causes of age-related disease, rather than just the symptoms. We are looking forward to engaging with the wider community for support in the pursuit of this important mission”, said Damian Crowe, Managing Trustee.

The BGRF will actively pursue and encourage projects identified by its scientific team as key to these goals. The science of the projects will be screened by a Scientific Advisory Board consisting of world-class researchers in biogerontology and related fields, in consultation with external experts as appropriate. Although these projects may be long term in nature, they will be designed to generate interim results and products that create academic and commercial interest, thereby bringing further resources into play and accelerating progress. As a key component of this strategy, The BGRF will seek appropriate Intellectual Property protection to encourage industry to apply the results of our projects quickly. Our long-term goal is to provide medical practitioners with the tools they need to enable effective and lasting remedies for illnesses and disabilities of old age.

Donations to the BGRF are welcome. For more information on how to donate to the BGRF or provide qualified services on a volunteer basis, please contact Alex Zhavoronkov, PhD at alex.zhavoronkov@bg-rf.org.uk .

Details on the Charities Commission for England and Wales registration are available at charity-commission.gov.uk/registeredcharities/showcharity.asp?remchar=&chyno=1124054.

About The Biogerontology Research Foundation:

The Biogerontology Research Foundation seeks to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF will fund research which, building on the body of knowledge about how ageing happens, will develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce the effective, lasting treatments for the diseases and disabilities of ageing, which are required to improve quality of life in the elderly. The BGRF seeks to use the entire scope of modern biotechnology to attack the changes that take place in the course of aging, and to address not just the symptoms of age-related diseases but also the mechanisms of those diseases.

About The Charity Commission for England and Wales

The Charity Commission for England and Wales is established by law as the regulator and registrar of charities in England and Wales. The aim of the Charity Commission is to provide the best possible regulation of these charities in order to increase charities’ efficiency and effectiveness and public confidence and trust in them.

The Charity Commission for England and Wales publication The Charity Commission and Regulation describes in more detail Commission’s values and operation as a regulator.

Announcements

9th June: Biogerontology Research Foundation Registered as a UK Charity

Formally announced on 9th june, the BGRF was registered as UK Charity 1124054 on 14th May. Full details in the press release.

30th May: Alex Zhavoronkov Voted as BGRF Trustee

The original trustees of the BGRF are delighted that Alex accepted their invitation to join them. Alex is the head fundraiser of the BGRF, and shares the rest of the team’s passion about fighting the diseases of ageing.

Leading Articles

Calorie Restricted Diet and Longevity

Calorie Restriction (CR) is a diet in which calorie intake is reduced, as compared to diets that do not limit consumption. Calorie Restriction with Optimum Nutrition (CRON), also called the Longevity Diet, has the potential to increase the average and maximum life span. CR is best characterized as undernutrition without malnutrition. Optimum Nutrition consists of eating the right amounts of nutrients on a proper schedule to achieve the best performance and the longest possible lifetime in good health.

This theory of the life-extending effect of reduced-calorie diets was reported in first 1935. It has been proved true for many species including yeasts, worms, mice and rats. Many mechanisms have been proposed to try to explain why CR increases life span, though as yet there is no clear consensus. Researchers have not been able to determine if humans on calorie restricted diets will live longer, but preliminary observations of the physiological changes caused by CR indicate that life-extending effects will probably be observable in humans also.

A test conducted on the genes of baker’s yeast combined with a low-calorie diet has resulted in increasing the lifespan of the yeast by a factor of 10.

Valter Lango and his team from the University of Southern California, Los Angeles, created a strain of yeast that lacks the genes RAS2 and SCH9. These genes are linked with ageing in yeast, and have been implicated in cancer in humans. Research was conducted to increase the lifespan of the yeast by keeping it on a calorie-restricted diet. The results led to extended life of the yeast from one to ten weeks, and without any evident side effects.

Similar research conducted by Sinclair’s lab reportedly found small molecules (e.g. resveratrol) that activate Sir2/SIRT1 and extend the lifespan of yeast, nematode worms, fruit flies, and mice consuming a high caloric diet.

Previous studies indicate that calorie restriction increases the lifespan of mammals and this technique is now being tried on mice. However, mutations associated with longevity often cause problems. A study is also being conducted on the people of Ecuador whose natural genetic mutations are similar to those of long-lived yeast.

Sources: http://www.scientificpsychic.com/health/crondiet.html
http://www.newscientist.com/article/mg19726404.700-scientists-find-fountain-of-youth–for-yeast.html

Premature Ageing: After-Effects of Cigarette Smoking

Modern gene research has reaffirmed the truth in the timeless saying; cigarette smoking is injurious to health. Latest research shows that smoking disables a gene, SIRT1 (Silent Mating Type Information Regulation 2 homolog 1), present in the lungs.

SIRT1 helps control premature ageing by reducing stress, cell death, and destructive inflammation of the lungs. Without the protection provided by SIRT1 the lungs become susceptible to chronic obstructive pulmonary disease (COPD) and lung cancer. Environmental stress such as cigarette smoke or pollution decreases production of surtuin 1 in the lungs.

Irfan Rahman, Professor of Environmental Medicine, University of Rochester, says, “This novel protein will allow us to program our body’s immune-inflammatory system against lung damage and premature aging. The hallmark of this discovery is that we may be able to provide remedies to millions of smokers who would like to quit but cannot kick their addiction, and millions of former smokers who, despite quitting, remain at risk for illness as they age.”

Professor Rahman has spent years studying the 4700 toxic chemical compounds found in cigarettes damaging the lung tissue. Professor Rahman’s team along with Vuokko L. Kinnula, M.D., at Helsinki University Hospital in Finland, studied the levels of SIRT1 in the lungs of nonsmokers and smokers with and without COPD. Thirty-seven patients from Helsinki, who were undergoing either a lung resection for suspected cancer or a lung transplant, volunteered to provide tissue samples for the study. Researchers confirmed that the activity of SIRT1 was significantly lower in smokers who had COPD and in smokers who did not have disease, compared to nonsmokers.

Scientists are also hoping to find ways to reverse the lung damage.

Source: http://www.cbc.ca/health/story/2008/01/24/smoking.html

Aging with poise by scrapping the scrap

Autophagy, or autophagocytosis, is a catabolic process involving the degradation of a cell’s own components through the lysosomal machinery. It is a major mechanism by which a starving cell reallocates nutrients from unnecessary processes to more essential processes. Scientists at the Salk Institute for Biological Studies reported that “Boosting autophagy in the nervous system of fruit flies prevented the age-dependent accumulation of cellular damage in neurons and promoted longevity.”

The age-related accumulation of proteins and lipids damaged by chemically aggressive forms of oxygen is considered by most in the geriatrics field to be a normal part of the aging process. Consequently, in most age-associated diseases, such as Alzheimer’s, damaged proteins accumulate in excessive amounts, which leads to progressive cell death in the brain.

All cells undergo autophagy – literally self-eating – which requires the assembly of specialized vesicles called autophagosomes. These vesicles surround or engulf damaged cellular proteins or structures and then traffic the “bagged garbage” to a second group of vesicles, which disposes off the trash with the help of digestive enzymes. This process can be enhanced when animals are placed on a calorie-restricted diet, a regime known to extend lifespan.

“The activation of autophagy facilitates the removal of damaged molecules that accumulate during cellular aging,” says Finley from the Salk Institute. “This may be particularly important in the nervous system since neurons produce damaged molecules at a much higher rate than most cell types.” Keeping cells free of damaged molecules is critical for neurons because unlike many cells, they do not divide or replace themselves once created at birth. “They rely on autophagy together with other clearance and detoxification pathways to keep themselves healthy and functioning for decades,” explains Finley.

Studies by the Salk researchers on the fruit fly Drosophila indicated that the expression of several autophagy genes decreased over the normal lifespan of fruit flies. The Salk researchers mainly focused on one particular protein, Atg8a (an essential component for the formation of new autophagosomes). The levels of Atg8a were significantly reduced by four weeks of age, a time when the flies are considered middle aged. At the same time, protein aggregates were not efficiently cleared by the cellular clean-up crew and started to accumulate.

Without Atg8a, damaged proteins marked for degradation started accumulating early and life expectancy dropped. “The abnormal accumulation of protein aggregates had striking similarities to those seen in the most common human neurodegenerative diseases,” says first author Anne Simonsen, Ph.D., a visiting scientist from the University of Oslo, Norway.

With the increase in the neuronal levels of Atg8a prevented the accumulation of protein aggregates and extended the average lifespan. “Our experiments show for the first time genetically that autophagy can sequester and eliminate misfolded and damaged proteins, which accumulate in neurons as normal part of the aging process,” says Simonsen, “but most importantly they demonstrate that enhancing the clearance of damaged proteins and protein aggregates increases longevity.”

Source: http://www.salk.edu/news/news_press_details.php?id=192

Digest

Digest: Scientific

Another Way Your Aging Immune System Harms You (May 23 2008)

http://pmid.us/18495785

An interesting paper: “Recent studies suggest that activation of the peripheral immune system elicits a discordant central (i.e., in the brain) inflammatory response in aged but otherwise healthy subjects compared with younger cohorts. A fundamental difference in the reactive state of microglial cells in the aged brain has been suggested as the basis for this discordant inflammatory response. Thus, the aging process appears to serve as a ‘priming’ stimulus for microglia, and upon secondary stimulation with a triggering stimulus (i.e., peripheral signals communicating infection), these primed microglia release excessive quantities of proinflammatory cytokines. … there is a propensity for this response to be maladaptive in aged subjects, resulting in greater severity and duration of the sickness behavior syndrome.” Your immune system evolved for a life span of a few decades, optimized to help you live long enough to pass on genes. It’s all downhill after that, as some of those optimizations start to be actively harmful later on in life. Repairing these deficiencies in the aging immune system is an important component for extending healthspan.

Upgrading Cells With Artificial Organelles (May 23 2008)

http://technology.newscientist.com/article/dn13967-cell-organs-get-plastic-upgrades.html

If you can build artificial cells, why not build artificial organelles within natural cells? From the New Scientist, a look at the future: “Human cells could have their metabolisms upgraded without altering their genes by inserting tiny plastic packages of enzymes … [researchers] coated their polymer vesicles in a chemical that encouraged human white blood cells called macrophages to engulf them. The small capsules contained enzymes, just like natural organelles. The enzymes chosen produced fluorescent chemicals, signalling they were working without problems inside their new host. … Artificial organelles might also be able to treat conditions caused by a deficit of a particular enzyme. For example, someone with lactose intolerance could have their digestive cells given artificial organelles containing lactose-digesting enzymes. In the far future, it might be possible to introduce non-human metabolic functions into human cells. … We could, in principle, bring in a nanoreactor that [lets] your skin do something like photosynthesis. So if you are hungry, you just lie in the sun.” Flights of fancy aside, it is easy to imagine many other, more directly beneficial, applications of this technology: for example, enzymes to degrade damaging aggregates that accumulate with age.

Essays From the Aging 2008 Event at UCLA

http://www.fightaging.org/archives/001487.php

“The difference between us and cars is that we know everything there is to know about repairing cars. Just as a Ferrari would have been impossibly complex to build two hundred years ago, so is the body today. The difference is that biology is quickly becoming an information science. As loyal readers of this column know, information technologies increase at an exponential rate. Just like computers, biotechnology such as DNA sequencing or fMRI imaging roughly doubles in capability every year. We will soon be able to deal with the nanoscale devices that make up the human machine and fix the damage that occur to them.”

http://www.fightaging.org/archives/001486.php

“Age-defying creams and lotions, esoteric herbs and elixirs, botox and plastic surgery, what do they all have in common? None of them will actually increase your lifespan. Usually, they’re snake oil. At best, they improve external appearance without actually extending life. We deserve better, and we’ll need it if we want to live longer than the typical four score and ten years.”

Understanding Embryonic Stem Cells (May 22 2008)

http://www.sciencedaily.com/releases/2008/05/080521131538.htm

ScienceDaily notes new knowledge that will lead to greater and more effective control over totipotent stem cells: “Our study suggests that what we believe about how embryonic stem cell self-renewal is controlled is wrong. Our findings will likely change the research direction of many stem cell laboratories. … Contrary to the current understanding of stem cell self-renewal and differentiation, the findings suggest that embryonic stem cells will remain undifferentiated if they are shielded from differentiation signals. By applying small molecules that block the chemicals from activating the differentiation process, the natural default of the cell is to self-renew, or multiply, as generic stem cells. … This study presents a completely new paradigm for understanding how to grow embryonic stem cells in the laboratory. The discovery has major implications for large scale production of specialized cells, such as brain, heart muscle and insulin producing cells, for future therapeutic use.” Replacing cells lost to aging is one important part of any suite of healthspan-extension therapies, and advances that bring that goal closer are welcome.

Improving Gene Therapy Thirtyfold (May 21 2008)

http://www.sciencedaily.com/releases/2008/05/080520090529.htm

When watching progress in medical science, you have to keep your eye on developments away from the headlines, such as improvements in infrastructure and methodology. It is progress at that level that enables the later big, bright advances that capture all the attention. Here’s an example from ScienceDaily: “geneticists say they have developed a new version of the adeno-associated virus used in gene therapy that works about 30 times more efficiently in mice than vectors scientists currently rely on … Based on our studies and those of others, it’s become clear that the reason you need so much is because about half the [adeno-associated virus (AAV)] particles get stuck in the cytoplasm. It doesn’t get to the nucleus very efficiently. The reason for that is obvious. AAV is seen by the body as an invading protein and it tries to block it … We didn’t change anything except the amino acid that does not allow phosphorylation to occur … We were very surprised. It’s amazing to think that changing one amino acid could produce these results.” Gene therapy is a very important tool, and order-of-magnitude improvements in cost and efficiency here will ripple out through the cutting edge of medical research – including many areas important to the longevity medicine of tomorrow.

Growing Body Parts In the Laboratory (May 20 2008)

http://www.redorbit.com/news/health/1390940/
growing_body_parts_in_the_lab_becomes_reality/

RedOrbit looks at tissue engineering: “Other alternatives to organ transplants have proved elusive. Transplants from animals, for example, face serious risks of rejection or viral infections. And mechanical organs, such as heart pumps, have been only a temporary solution. … If we want to live forever, we need to do better … Engineering body parts – tissues and whole organs that are genetically compatible and available on demand – sounds like science fiction. But researchers at medical centers around the world are working to make it a reality. Already, a handful of children with spina bifida have received new bladders. Replacement blood vessels are being tested on dialysis patients. And researchers have re-created a beating rat heart. … [The] first wave of tissue engineering did yield some useful products, such as artificial skin grafts that are used to treat diabetic skin ulcers. But many of the awe-inspiring breakthroughs that scientists are talking about are still many years away … The real potential for tissue engineering is the vital organs, but we’re a ways away from that, even though there’s some exciting things being done.” The article looks at some of the more recent advances in engineering blood vessels, building complete hearts using a novel scaffold method, and of work on tissue engineered bladders.

More Progress Towards Alzheimer’s Vaccines (May 19 2008)

http://www.eurekalert.org/pub_releases/2008-05/uorm-vti051908.php

EurekAlert! reports on another promising Alzheimer’s vaccine in the works: “Vaccinated mice generated an immune response to the protein known as amyloid-beta peptide, which accumulates in what are called ‘amyloid plaques’ in brains of people with Alzheimer’s. The vaccinated mice demonstrated normal learning skills and functioning memory in spite of being genetically designed to develop an aggressive form of the disease. … vaccinated mice not only performed better, we found no evidence of signature amyloid plaque in their brains … The mice [also] harbored a mutation that causes the tau-related tangle pathology … What we found exciting was that by targeting one pathology of Alzheimer’s – amyloid beta – we were able to also prevent the transition of tau from its normal form to a form found in the disease state … due to the number of studies required to satisfy regulatory requirements, it could be three or more years before human trials testing this type of Alzheimer’s vaccine occur.”

Digest: Economic, Political and General

UK Dementia Costs Set to Soar

A recent report by the Kings Fund, a heathcare charity and think-tank, has quantified the expected rise in costs due to age-related dementia. Around 50% of people in their eighties experiences dementia, and the report predicts that as the baby-boom generation reaches this age in the new few decades costs for their care will rise to a staggering Ј47 billion annually. This is potentially an unsustainable load on the public finances, and will be mirrored across the world. This is another illustration of just why the BGRF and others’ focus on healthspan extension is so vital, in additon to the humanist arguments of reducing suffering.

Pension Industry Forsees Rising Life Expectancy

http://news.bbc.co.uk/2/hi/business/7413120.stm

The pension, insurance and actuarial sectors tend to be conservative in their outlook, but they stand to mimimise their future exposure by producing the best possible predictions on life expectancy. Here’s an update from the BBC on a few of the changes that have been taking place in the past few years: “Many UK companies are now assuming their male pensioners will live, on average, one year longer than they assumed in 2006. … It’s interesting they are going by one year, every year. There is an element of catch-up but there is great uncertainty about how this trend will go in the future.” The uncertainty is further fuelled by the tremendous promise offered by current research programmes.