Longevity Meme Newsletter, May 17 2010

May 17 2010

The Longevity Meme 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 the Longevity Meme.



- A Little Perspective
- On Genetic Contributions to Extreme Longevity
- The Longevity Consortium
- Discussion
- Latest Healthy Life Extension Headlines


Looking at the broader picture:


"The growth in health, welfare, and wealth of 18th century Europe was a glittering spire when set against any measure of the grand history of humanity. A pinnacle set abruptly at the end of a very long, very gentle upward slope. ... Disease, parasitism, pain, suffering, and a short life is the unvarnished and absolutely natural human condition, absent our marvelous talent for progress. That talent, compounded over the course of history, ensured that the 18th century was a time of great change and increasing life spans. But by the year 1900, those earlier heights of medicine and wealth were shown to be mere foothills and swamps of ignorance in comparison to the new knowledge won by scientific and medical pioneers. Fast forward another hundred years, to our present age, and 1900 now seems like a dim echo of a pastoral past, a quaint era of ignorance, crude medicine, lives cut short by untreatable age-related disease, and earnest poverty - all captured for posterity in fading black and white photographs."

Yet you don't have to go far to find people who think that we're somewhere near the apex of medicine, and that there won't be much progress in extending the healthy human life span in the years ahead. A strange viewpoint, when considered against the course of human history.


The Royal Society in the UK recently held a meeting on aging research, and an interview with presenter Nir Barzilai made clear that some researchers believe there to exist genetic variants that have a strong effect on human life expectancy:


"[Barzilai] studied 500 Jewish people between 95 and 112. He said: 'These people smoked, they are overweight, they have high cholesterol.' Qualifying his remarks, he said about 30 per cent of them were obese, while 30 per cent of them had smoked to the age of 95. 'They are protected from the environment by their genotype,' he said. Living a healthy life might help most people increase their life expectancy by a few years, but it would not help those who wanted to live much longer, he said. ... 'When they eventually die, they die of the same things that people die of in their 70s or 80s,' he said, 'it's just that they die 30 years later'. Identifying these genes opened the doorway to developing longevity drugs which mimicked their effects, he said."

Live healthily not because you think it will let you survive into the far outskirts of present human longevity, but because it will increase your chances of living in good health to benefit from future developments in medical science. The older we get, the more our remaining life span and health is determined by progress in advanced medical technologies - which suggests that we should all be doing more now to support the best and most promising research. For example, by donating to the Methuselah Foundation or SENS Foundation:



The Longevity Consortium is an interesting project, and its members are a representative cross-section of the mainstream of modern aging research - which is to say people who largely focus on understanding aging only, or on slowing aging by manipulating metabolism:


"We are a consortium of scientists from multiple disciplines interested in the study of genetics of aging and age-related traits. Our group includes laboratory-based scientists, epidemiologists and statistical geneticists. Members of the Consortium represent three types of research efforts: (a) Laboratories devoted to the identification of longevity-related genes and pathways in non-human species; (b) Studies of special populations (e.g., centenarians) that are engaged in the discovery of genes associated with longevity; and (c) Established longitudinal cohorts of elderly men and women that have DNA and excellent phenotyping that can be used to study candidate genes."


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!




A new technique for tissue engineering: "Tissue engineering has long held promise for building new organs to replace damaged livers, blood vessels and other body parts. However, one major obstacle is getting cells grown in a lab dish to form 3-D shapes instead of flat layers. ... To obtain single cells for tissue engineering, researchers have to first break tissue apart, using enzymes that digest the extracellular material that normally holds cells together. However, once the cells are free, it's difficult to assemble them into structures that mimic natural tissue microarchitecture. Some scientists have successfully built simple tissues such as skin, cartilage or bladder on biodegradable foam scaffolds. ... That works, but it often lacks a controlled microarchitecture. You don't get tissues with the same complexity as normal tissues. ... Researchers [have] come up with a new way to overcome that challenge, by encapsulating living cells in cubes and arranging them into 3-D structures, just as a child would construct buildings out of blocks. The new technique, dubbed 'micromasonry,' employs a gel-like material that acts like concrete, binding the cell 'bricks' together as it hardens. ... You can reproduce this in any lab. It's very simple. ... The short-term next step is really looking at different cell types and the viability of tissue growth."

Via EurekAlert: "Humans are born with 30,000 cochlear and vestibular hair cells per ear. (By contrast, one retina harbors about 120 million photoreceptors.) When a significant number of these cells are lost or damaged, hearing loss occurs. The major reason for hearing loss and certain balance disorders is that - unlike other species such as birds - humans and other mammals are unable to spontaneously regenerate these hearing cells. ... After years of lab work, researchers [have] found a way to develop mouse cells that look and act just like the animal's inner-ear hair cells - the linchpin to our sense of hearing and balance - in a petri dish. If they can further perfect the recipe to generate hair cells in the millions, it could lead to significant scientific and clinical advances along the path to curing deafness in the future. ... While researchers will ultimately need human hair cells, the mouse version is a good model for the initial phases of experimentation, he said. In addition to using mouse embryonic stem cells, the researchers used fibroblasts that had been reprogrammed to behave like stem cells: These are known as induced pluripotent stem cells, or iPS cells."

From the SENS Foundation: "To date, all successful interventions into the biological aging process in experimental animals have entailed modulation of basic metabolic pathways, generally through genetic or dietary manipulation. Of these, the earliest, most well-studied, and arguably the most robust, is Calorie restriction (CR): the reduction in dietary energy intake, without compromise of essential nutrients. With few exceptions, CR retards the biological rate of aging in nearly every species and strain of organisms in which it has been tested, ranging from rotifers, through small multicellular invertebrates, and most extensively to laboratory rodents; and although inconclusive, recent evidence also supports its effectiveness in dogs and nonhuman primates. Moreover, while necessarily preliminary, a growing body of human research has reported that rigorous CR, when practiced by previously normal-weight adults, results in physiological, functional, and perhaps even structural changes consistent with its translation to the human case. ... But despite the initial attractiveness of the notion; its strong theoretical basis; the high level of scientific interest that it has garnered; the launching of biotech startups originating in CR mimetic research; and the popularization and commercial exploitation of the concept by the dietary supplement industry - despite all of these drivers, the ensuing decade and a half or more of CR mimetic research have thus far been fruitless. Initially-promising compounds have failed to extend lifespan, while surprising findings have preempted the further investigation of what might otherwise have been novel targets for CR mimetics."

From QFinance: "Big business and governments are already grappling with the uncomfortable side effects of increasing longevity. According to actuaries, the present generation has gained the equivalent of 12 minutes an hour or a 20% increase in average lifespan by comparison with the previous generation. The impact of this is felt first and foremost in the pensions arena, with businesses having to run harder just to stand still as far as their pension scheme deficits are concerned. But it is felt too by governments across Europe as they struggle to pay out meaningful state pension benefits against the headwind imposed by the fact that the ratio of those in work to those on pension is getting more and more out of balance. The impact of increased longevity is felt too in the health systems, where the diseases and ailments of old age take an increasing toll on a country's medical resources. These problems might seem fairly intractable, or at least extremely difficult and challenging in their own right, but it could be just the tip of the iceberg, according to the renowned longevity specialist Dr Aubrey de Grey, Chief Scientist at the charity SENS, which specializes in promoting research that aims to 'defeat ageing.' Dr de Grey is famous for asserting that the first person to enjoy a four-digit lifespan is probably already in his or her middle years. Before I give a rapid summary of his reasoning - those interested in learning more can watch a video of one of his presentations at the SENS website - it is worth saying that if de Grey is right, then instead of exacerbating the pensions problem, as I suggested earlier, it will probably make the problem vanish like a puff of smoke. Provided society stays reasonably open, people will have more than enough time to acquire independent means. The magic of compound arithmetic will be very much in their favor. Start small, watch it grow, where's the hurry?"

An open access paper from Impact Aging: "The Mitochondrial Free Radical Theory of Aging (MFRTA) is currently one of the most widely accepted theories used to explain aging. From MFRTA three basic predictions can be made: long-lived individuals or species should produce fewer mitochondrial Reactive Oxygen Species (mtROS) than short-lived individuals or species; a decrease in mtROS production will increase lifespan; and an increase in mtROS production will decrease lifespan. It is possible to add a further fourth prediction: if ROS is controlling longevity separating these parameters through selection would be impossible. These predictions have been tested in Drosophila melanogaster." Where I think the researchers go wrong here lies in not accounting for how differences in mitochondrial composition might affect the level of damage caused by a given amount of ROS. There is a strong argument that species life span differences have a lot to do with how resilient mitochondria are to damage. But read the paper anyway; it's a good introduction to thinking about the mitochondrial free radical theory of aging.

As this Independent article shows, the public view of longevity science extends little beyond the goal of slowing aging espoused by mainstream researchers, and conflates the fakery and fraud of "anti-aging" cosmetics companies with real science: "We spend millions of pounds each year on anti-ageing tonics, potions, vitamins and creams, trying to stave off the ravages of the years. But our genetic inheritance trumps all other factors in determining how well we age and how long we live. By unravelling the genetic determinants of longevity, scientists believe they will be able to manipulate them to add not only years to life, but also life to years. An elixir of youth remains a distant dream but medicines to help us live longer and better are moving closer. At a conference this week, Turning Back the Clock, organised by the Royal Society, researchers described the progress that has been made in the science of ageing. At least 10 gene mutations have been identified that extend the lifespan of mice by up to half, and in humans several genetic variants have been linked with longevity. They include a family of genes dubbed the sirtuins, which one Italian study found occurred more commonly in centenarian men than in the general population. A subsidiary of drug giant GlaxoSmithKline is now looking at sirtuins, and their association with a range of age-related diseases including type 2 diabetes and cancers."

Another consequence of the overeating and lack of exercise that leads to metabolic syndrome and diabetes: "In people with insulin resistance or full-blown diabetes, an inability to keep blood sugar levels under control isn't the only problem by far. A new report [shows] that our arteries suffer the effects of insulin resistance, too, just for entirely different reasons. ... Earlier studies showed that in the context of systemic insulin resistance, blood vessels become resistant, too. Doctors also knew that insulin resistance and the high insulin levels to which it leads are independent risk factors for vascular disease. But it wasn't clear if arteries become diseased because they can't respond to insulin or because they get exposed to too much of it. Now comes evidence in favor of the former explanation. ... mice prone to atherosclerosis fare much worse when the linings of their arteries can't respond to insulin. The animals' insulin-resistant arteries develop plaques that are twice the size of those on normal arteries. Insulin-resistant blood vessels don't open up as well, and levels of a protein known as VCAM-1 go up in them, too. VCAM-1 belongs to a family of adhesion molecules [which sit on the endothelium and bind] white blood cells. ... Those cells can enter the artery wall, where they start taking up cholesterol, and an early plaque is born. ... The results provide definitive evidence that loss of insulin signaling in the endothelium, in the absence of competing systemic risk factors, accelerates atherosclerosis."

Autophagy is important in determining life span, probably because of its role in clearing out damaged mitochondria (a process known as mitophagy) before they can cause other forms of harm. Here is evidence for that view in the form of a link between Parkinson's disease and autophagy: "Mutations that cause Parkinson's disease prevent cells from destroying defective mitochondria ... Defects in the ubiquitin ligase Parkin are linked to early-onset cases of this neurodegenerative disorder. The wild-type protein promotes the removal of impaired mitochondria by a specialized version of the autophagy pathway called mitophagy, delivering mitochondria to the lysosomes for degradation. Mitochondria are often dysfunctional in Parkinson's disease ... cells expressing mutant forms of Parkin failed to clear their mitochondria after the organelles were damaged. Different mutations blocked mitophagy at distinct steps: mitochondria accumulated in the perinuclear region of cells expressing Parkin lacking its ubiquitin ligase activity, for example. The researchers found that ubiquitination of defective mitochondria by Parkin normally recruits the autophagy proteins HDAC6 and p62 to clear these mitochondrial aggregates. ... The clearance of defective mitochondria is therefore similar to the removal of damaged proteins, another autophagic process that goes wrong in Parkinson's disease resulting in the accumulation of toxic protein aggregates. Both pathways rely on microtubules, HDAC6, and p62, [providing] a common link between the two main features of the neurodegenerative disorder."

From ScienceDaily: researchers "have found that the level of a single protein in the tiny roundworm C. elegans determines how long it lives. Worms born without this protein, called arrestin, lived about one-third longer than normal, while worms that had triple the amount of arrestin lived one-third less. ... arrestin interacts with several other proteins within cells to regulate longevity. The human version of one of these proteins is PTEN, a well-known tumor suppressor. ... The links we have found in worms suggest the same kind of interactions occur in mammals although human biology is certainly more complicated. We have much work to do to sort out these pathways, but that is our goal. ... We don't know at this point if human arrestins regulate PTEN function or if anything happens to arrestin levels during the development of cancer. Do increasing levels turn off more PTEN, thus promoting cancer, or do levels decrease and allow PTEN to be more active? ... If it turns out to be the first scenario - that increasing amounts of arrestin turn off the tumor suppressor activity of PTEN, then it may be possible to selectively inhibit that process. We have some interesting work ahead."

From EurekAlert!: "Human adult stem cells injected around the damage caused by a heart attack survived in the heart and improved its pumping efficiency for a year in a mouse model ... Injection of a patient's own adult stem cells into the heart has shown some efficacy in assisting recovery after a heart attack in early human clinical trials, [but] nobody knows how they work, or how long the stem cells last and function in the heart. This study shows how one type of adult stem cell works. ... The team's research focused on adult stem cells – those that can differentiate into a limited variety of tissues – that circulate in the blood and are distinguished by the presence of the CD34 protein on the cell surface. ... CD34+ cells are capable of becoming heart muscle cells, called cardiomyocytes, blood vessel cells and smooth muscle cells. ... The CD34+ cells survived in the left ventricle of the heart for 12 months or longer. Left ventricular ejection fraction - a measure of how much blood is pumped from the heart to other organs at each contraction - improved in treated mice compared with controls for 52 weeks. ... This improvement was the result of increased blood vessel formation in and around the injured area, or paracrine signaling by the stem cells to other nearby cells, rather than formation of new heart muscle."



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