FIGHT AGING! NEWSLETTER
December 12th 2011
The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!
- SENS Foundation Academic Initiative Grants in 2012
- Granulocyte Infusion Therapy Spreading Beyond the US
- Fitness, Fatness, and Longevity
- Latest Headlines from Fight Aging!
SENS FOUNDATION ACADEMIC INITIATIVE GRANTS IN 2012
One part of the necessary present work on rejuvenation biotechnology is to ensure that there exists a growing, enthusiastic research community for this field ten and twenty years from now. That means outreach, education, and persuasion aimed at bringing more young life scientists into aging and longevity research today:
"In addition to funding and coordinating research into rejuvenation biotechnology, the SENS Foundation runs an Academic Initiative program that aims to pull more people into the field at an early stage in their life science careers. We must all bear in mind that turning the vision of ways to repair the biological damage of aging into the reality of suitable therapies will be the work of several decades in the best of circumstances. We have a very clear vision of the path ahead and what needs to be done in detail to repair an old human or prevent a young human from becoming old - but it will still require decades to achieve the end goal. The fastest plausible path to this future starts with a crash program that burns $1 billion in ten years to achieve rejuvenation in mice, but the research community is far from being able to deploy even a fraction of that level of resources and determination. Work proceeds slowly and there is a lot of work to do.
"Given that we are looking at 20 to 30 years passing between now and widespread first generation methods of limited age-reversal, it is important to put effort towards ensuring that there will be a growing, enthusiastic research community in the years ahead. Hence the Academic Initiative: building connections, guiding younger life scientists, and encouraging the best to work on the defeat of degenerative aging. In this vein, I see that the SENS Foundation is making a small number of grants for 2012 as a part of the Academic Initiative. Young and interested life scientists in the audience might want to take note."
GRANULOCYTE INFUSION THERAPY SPREADING BEYOND THE US
It is good to see that noteworthy medical advances that don't find a footing in the US are spreading as they should - into less over-regulated regions where they can be further developed and made available for medical tourism:
"You may recall the very promising form of cancer immune therapy pioneered by Zheng Cui that involves transplanting granulocytes from suitable donors - it performed very well indeed in mice, superbly in fact ... Unfortunately, one anemic trial and a little additional research is where things still stand, more or less. This is a funding and culture of medical development issue: it's not yet completely understood how the therapy works at the biochemical level, and the prevalent incentives are for research groups to strive to fully understand a mechanism so that they can apply for patents, develop drugs that manipulate those mechanisms, and so forth and so on. Fortunately, if work is well publicized and the scientific papers openly published, clinics and medical developers worldwide can get into the game - and not all of them have the same incentives as US-based scientists and other cancer research concerns. So I see that there is a clinic in Mexico called NCIM that is now offering granulocyte infusion treatment, for example."
A commenter also pointed out a more rigorous effort underway in China: This sort of thing is exactly what we'd like to see happen for the few already existing technology demonstrations that might form the basis of future therapies to repair specific aspects of aging. Since those scientific results cannot be legally further developed in the US, as the FDA will not approve treatments for aging under its present regulatory regime, developers, researchers, and clinicians in other regions must pick up the slack.
FITNESS, FATNESS, AND LONGEVITY
Not just a river in Africa:
"There is a great deal of denial floating around when it comes to the excess weight carried by a majority of the people fortunate enough to live in wealthier parts of the world - even more denial than there is for lack of exercise, and there's plenty of that. Wealth is ever a double-edge sword, and brings the opportunity to become overweight and sedentary along with its many benefits - we mammals have evolved to find it hard to turn down large amounts of food that is both cheap and good, and we've succeeded ourselves into a challenging position on that front. Unfortunately indulgence has meaningful costs: a deterioration in health and life expectancy, and the more we overeat the worse that cost becomes. This has always been the folk wisdom of past decades and centuries, but in recent years the life science and medical research communities have brought more rigorous measurement and greater understanding to the costs of excess fat tissue and lack of exercise. Denial is becoming harder - which is a good thing, as the cost of food will continue to head towards zero as technology advances."
The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!
LATEST HEADLINES FROM FIGHT AGING!
MORE ARGUMENTS FOR PROGRAMMED AGING
Friday, December 9, 2011
A viewpoint from Vladimir Skulachev, whose research group works on mitochondrially targeted antioxidant compounds: "'It is recognized that in exceptional circumstances the possibility exists for selection to favor limiting survival. In acknowledging that at least in theory, aging might occasionally be adaptive, however, the high barriers to validating actual instances of adaptive ageing are made clear' ... A few years ago it was hardly possible to find the latter statement in an article written by the most famous proponents of non-programmed aging. Certainly, this conclusion is accompanied by some reservations. Nevertheless, the balance between concepts of programmed and non-programmed aging seems to be really shifted to the programmed one. ... The idea that programmed death was invented by biological evolution was introduced in the end of nineteenth century by August Weismann, who suggested that such a death is useful for evolution as a mechanism which (i) purifies the population from weak individuals and (ii) promotes succession of generations. For sure, both these roles may be inherent in aging. However, they failed to explain why aging represents slow and concerted decline of many physiological functions (slow phenoptosis) rather than simple fast switching off of a single function of vital importance (acute phenoptosis). ... There is, it must be acknowledged, an instinctive attraction to the idea that aging is programmed. Aging is widespread across species and applies universally to all individuals within a species in which it is observed. There is also reproducibility about changes that occur with aging .... I may only add that, if aging is programmed, it can be retarded, prevented, and perhaps even reversed by treatments interrupting execution of this program, just as we already can interrupt programs of cell death. In other words, programmed aging can be cured like a disease. As for the concept of non-programmed aging, assuming occasional accumulation of stochastic injuries as its reason, it is quite pessimistic for finding any way of successful treatment. Here we simply observe and describe such a process without the possibility of improving the situation." This last viewpoint is exactly the wrong way around - repair of damage is likely to be far easier through SENS and similar programs than safely altering the exceedingly complex systems of metabolism to change the way in which aging happens. We should hope that genetic programs are of limited and narrow influence as a driver of aging - that they are merely reactions to underlying accumulations of damage where they exist at all. Because otherwise we're in for a long, slow road when it comes to extending healthy life.
COMMENTARY ON RAPAMYCIN
Friday, December 9, 2011
A commentary on recent research into the effects of rapamycin on longevity: "Aging is a complex process associated with accumulation of damage, loss of function and increased vulnerability to disease, leading ultimately to death. Despite the complicated etiology of aging, an important discovery of recent years has been that simple genetic alterations can cause a substantial increase in healthy lifespan in laboratory model organisms. Many of these longevity-extending mutations down-regulate the activity of the mTOR/S6K pathway suggesting that reduced Tor/S6K signaling promotes entry into alternative phases normally entered during periods of starvation. In fact, dietary restriction (DR), a reduction in food intake without malnutrition, lowers Tor/S6K signaling and extends the average and maximum life span of a variety of organisms including yeast, flies, worms, fish, and rodents. ... Recently, it has been demonstrated that supplementation with rapamycin (an inhibitor of mTOR) started both at 9 and 20 months of life determines a small but significant extension of average and maximal life span in genetically heterogeneous male and female mice ... More studies are needed to understand benefits and side-effects of rapamycin supplementation in different strains of mice and in monkeys as a candidate cancer-preventive and life-extension pharmacological agent. However, the efficacy of intermittent rapamycin treatment in cancer prevention and life span extension [is] very promising since it is likely to reduce the side effects associated with chronic treatment."
RESTORING SYNAPTIC PLASTICITY IN OLD RATS
Thursday, December 8, 2011
In the next few years were going to see a lot of technology demonstrations in which one very narrow biochemical aspect of aging is reversed in laboratory animals - these are the first few pebbles in what will become an avalanche of rejuvenation biotechnology. You might recall the reversal of lysosomal functional decline in the livers of mice in 2008 as an example of the type. Here is one for the brain: "Drugs that affect the levels of an important brain protein involved in learning and memory reverse cellular changes in the brain seen during aging, according to an animal study. ... [Aging] affects brain cells' ability to alter the strength and structure of their connections for information storage, a process known as synaptic plasticity, which is a cellular signature of memory. ... compared with younger rats, hippocampi from older rats have less brain-derived neurotrophic factor (BDNF) - a protein that promotes synaptic plasticity - and less histone acetylation of the Bdnf gene. By treating the hippocampal tissue from older animals with a drug that increased histone acetylation, they were able to restore BDNF production and synaptic plasticity to levels found in younger animals. ... The researchers also found that treating the hippocampal tissue from older animals with a different drug that activates a BDNF receptor also reversed the synaptic plasticity deficit in the older rats."
A PROMISING DISCOVERY FOR LUNG REGENERATION
Thursday, December 8, 2011
Via MedicalXPress: "researchers [put] forward a theory for the first time based on research evidence that new air sacs, called alveoli, are constantly being formed. This contradicts information in most medical textbooks that explain that the tiny air sacs begin to develop before birth (around the 6th month of pregnancy) and continue to increase in number until the age of about 3 years. ... It was believed that there was no further increase in the number of alveoli beyond that age, and that the existing alveoli just expanded as the lungs grew bigger until final adult size was reached. Our study has challenged this by suggesting that new alveoli continue to be formed as the lungs grow. ... The researchers studied over 100 healthy volunteers aged between 7 and 21 years. Each volunteer [breathed] in hyperpolarised helium and held their breaths. ... The helium [behaves] like a magnetised gas. Within the scanner, we can measure how the magnetism decays, and this in turn depends on the size of the air sacs - alveoli - which contain the helium. ... We studied small children, whose lungs contain approximately one litre of air, and full-grown adults with lung volumes of around four litres. We found very little difference in the size of the alveoli across everyone we studied. If the size of the alveoli are hardly changing, this can only mean one thing - as our lungs increase in size, we must be growing new alveoli. ... This research has important implications. If we can continue to develop new alveoli beyond early childhood, going on through adolescence, there is the potential for lung repair following injury that was never realised before."
CONSIDERING THE ODDS OF CANCER
Wednesday, December 7, 2011
To what degree can you swing the odds of suffering cancer in your favor? A fair amount, if this article is to be taken at face value, as much or more as other common age-related conditions: "Nearly half of cancers diagnosed in the UK each year - over 130,000 in total - are caused by avoidable life choices including smoking, drinking and eating the wrong things, a review reveals. Tobacco is the biggest culprit, causing 23% of cases in men and 15.6% in women, says the Cancer Research UK report. Next comes a lack of fresh fruit and vegetables in men's diets, while for women it is being overweight. ... Many people believe cancer is down to fate or 'in the genes' and that it is the luck of the draw whether they get it. Looking at all the evidence, it's clear that around 40% of all cancers are caused by things we mostly have the power to change. ... We didn't expect to find that eating fruit and vegetables would prove to be so important in protecting men against cancer. And among women we didn't expect being overweight to be more of a risk factor than alcohol. ... About 100,000 (34%) of the cancers are linked to smoking, diet, alcohol and excess weight. ... The researchers base their calculations on predicted numbers of cases for 18 different types of cancer in 2010, using UK incidence figures for the 15-year period from 1993 to 2007." As usual, excess fat and smoking show up as undesirables - they are there as prominent risk factors for most of the unpleasant things that aging inflicts upon us.
REPRODUCTIVE CELLS AND SOMATIC CELLS AGING ON DIFFERENT CLOCKS
Wednesday, December 7, 2011
Via EurekAlert!: "Reproductive and somatic aging use different molecular mechanisms that show little overlap between the types of genes required to keep oocytes healthy and the genes that generally extend life span. ... The different genetic pathways help explain why a woman's fertility begins to decline after she is 35 years old, while her other cells do not show significant signs of aging until decades later ... To compare the molecular mechanisms that are switched on or off with the aging of oocytes and somatic cells, Murphy's lab turned to the model organism, Caenorhabditis elegans (C. elegans), the worm-like nematode that set off the whole field of longevity research with the discovery in the 1990s that gene mutations affecting insulin regulation doubled the worm's life span.Using DNA microarrays to measure the expression levels of genes, Dr. Murphy and her colleagues noted a distinctive DNA signature for aging oocytes. They also found that the oocytes of aging insulin and transforming growth factor-beta (TGF-beta) mutant mice had the same DNA profile that characterized young females. The researchers then compared the oocyte gene expression patterns with microarray transcription data on worms carrying the famous long-life mutations. Murphy and her colleagues found that even though somatic and reproductive aging in C. elegans both involve the insulin regulation pathway, the molecular mechanisms to maintain youthful oocyte function and to combat body aging are very different. ... It seems that maintaining protein and cell quality is the most important component of somatic longevity in worms, while chromosomal/DNA integrity and cell cycle control are the most critical factors for oocyte health."
AMYLOID BETA AND TAU STILL LOOK LIKE GOOD TARGETS FOR DEMENTIA RESEARCH
Tuesday, December 6, 2011
A recent paper: "The emergence of longevity in the modern world has brought a sense of urgency to understanding age-related neurodegenerative diseases such as Alzheimer's disease. Unfortunately, there is a lack of consensus regarding the correlation between the pathological substrates of neurodegeneration and dementia status, particularly in the oldest-old. To better understand the pathological correlates of dementia in the oldest-old, we characterized the topographical spread and severity of amyloid-β, tau, TDP-43 and α-synuclein pathologies in the 90+ Study, a prospective longitudinal population-based study of ageing and dementia. ... We used quantitative and/or semi-quantitative measures to assess the burden of amyloid-β, tau, TDP-43 and α-synuclein pathologies as well as hippocampal sclerosis. Amyloid-β and tau were the predominant pathologies in the 90+ Study cohort and both amyloid-β area and tau area occupied measures were strongly associated with the presence of dementia ... Notably, TDP-43 pathology also correlated with dementia, while α-synuclein distribution did not. ... In contrast to previous reports, we found that tau and amyloid-β continue to be robust pathological correlates of dementia, even in the oldest-old."
LATER MENOPAUSE, LOWER MORTALITY RATE
Tuesday, December 6, 2011
If we think of aging as accumulated damage, then we should not be surprised to see a lower rate of mortality associated with later menopause. The timing of menopause is at least partially driven by the degree to which an individual is aging, just like losing hair, degree of skin wrinkling, loss of muscle mass, and so forth - it just happens to be easier to measure as a distinct event: "The reproductive-cell cycle theory of aging posits that reproductive hormone changes associated with menopause and andropause drive senescence via altered cell cycle signaling. Using data from the Wisconsin Longitudinal Study, we analyzed the relationship between longevity and menopause, including other factors that impact 'ovarian lifespan' such as births, oophorectomy, and hormone replacement therapy. We found that later onset of menopause was associated with lower mortality, with and without adjusting for additional factors (years of education, smoking status, body mass index, and marital status). Each year of delayed menopause resulted in a 2.9% reduction in mortality; after including a number of additional controls, the effect was attenuated modestly but remained statistically significant (2.6% reduction in mortality). We also found that no other reproductive parameters assessed added to the prediction of longevity, suggesting that reproductive factors shown to affect longevity elsewhere may be mediated by age of menopause. Thus, surgical and natural menopause at age 40, for example, resulted in identical survival probabilities. These results support the maintenance of the hypothalamic-pituitary-gonadal axis in homeostasis in prolonging human longevity, which provides a coherent framework for understanding the relationship between reproduction and longevity."
ENGINEERING CARTILAGE REPLACEMENTS
Monday, December 5, 2011
The structural properties of natural cartilage have proven challenging to recreate in tissue engineering, but researchers are making progress: "A lab discovery is a step toward implantable replacement cartilage, holding promise for knees, shoulders, ears and noses damaged by osteoarthritis, sports injuries and accidents. Self-assembling sheets of mesenchymal stem cells permeated with tiny beads filled with growth factor formed thicker, stiffer cartilage than previous tissue engineering methods. ... We think that the capacity to drive cartilage formation using the patient's own stem cells and the potential to use this approach without lengthy culture time prior to implantation makes this technology attractive ... The team put transforming growth factor beta-1 in biodegradable gelatin microspheres distributed throughout the sheet of stem cells rather than soak the sheet in growth factor. ... The microspheres provide structure, similar to scaffolds, creating space between cells that is maintained after the beads degrade. The spacing results in better water retention - a key to resiliency. The gelatin beads degrade at a controllable rate due to exposure to chemicals released by the cells. As the beads degrade, growth factor is released to cells at the interior and exterior of the sheet, providing more uniform cell differentiation into neocartilage. The rate of microsphere degradation and, therefore, cell differentiation, can be tailored by the degree to which the microsphere are cross-linked. ... After three weeks in a petri dish, all sheets containing microspheres were thicker and more resilient than the control sheet. The sheet with sparsely crosslinked microspheres grew into the thickest and most resilient neocartilage."
GROWING EYES, GLANDS, AND BRAIN TISSUE
Monday, December 5, 2011
The Guardian looks at the activities of one Japanese research group: "In the latest of a series of remarkable studies, researchers from the RIKEN Center for Developmental Biology in Kobe, Japan report that embryonic stem cells grown under special conditions can spontaneously organize themselves into a partial pituitary gland that is fully functional when transplanted into mice. ... Over the past four years, Yoshiki Sasai and his colleagues of RIKEN's Organogenesis and Neurogenesis Group have developed a novel cell culture technique for growing embryonic stem (ES) cells in floating three-dimensional aggregates. ... In 2008, Sasai's group showed that ES cells grown in 3D cultures can recapitulate the earliest stages of neural development to self-organize into functional brain tissue, which integrated into existing neural circuits when transplanted into the brains of newborn mice. And earlier this year, they reported ES cells can also generate embryonic eyes with retinas. ... Growing complete, fully functional organs for transplantation is the holy grail of regenerative medicine, one which is being pursued by many groups of researchers around the world. ... Sasai's group is at the forefront of these efforts. Their work shows that ES cells can spontaneously form complex three-dimensional structures when grown under the right conditions, in the absence of a scaffold. With each new study, they demonstrate the generation of increasingly complex structures, and the pituitary gland is the most complex one yet."