Fight Aging! Newsletter, April 1st 2013

April 1st 2013

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!



- Why Prioritize SENS Research for Human Longevity?
- Induced Pluripotency Removes Some Markers of Cell Age
- A Late Tissue Engineering Year in Review for 2012
- A Surprising Lack of Age-Related Degeneration in Muscles
- Discussion
- Latest Headlines from Fight Aging!
    - Metformin May Act to Reduce Chronic Inflammation
    - More on CD47 as a Potentially Broad Cancer Therapy Target
    - On Nanoscale-Featured Scaffolds in Regenerative Medicine
    - An Investigation into Rates of Aging and Heart Disease Risk
    - Amniotic Fluid Stem Cells Spur Repair of Gut Damage
    - Building Functional Ovarian Tissue
    - On Autophagy in Stem Cells
    - An Analysis of Mitochondrial Dysfunction in Aging and Disease
    - A Popular Science Article on Organ Engineering
    - SENS6 Conference Registration Open


Why do I vocally support rejuvenation research based on the Strategies for Engineered Negligible Senescence (SENS) over other forms of longevity science? Why do I hold the view that SENS and SENS-like research should be prioritized and massively funded? The short answer to this question is that SENS-derived medical biotechnology has a much greater expected utility - it will most likely produce far better outcomes, and at a lower cost - than other presently ongoing lines of research into creating greater human longevity.

But firstly, what is SENS? It is more an umbrella collection of categories than a specific program, though it is the case that narrowly focused SENS research initiatives run under the auspices of the SENS Research Foundation. On the science side of the house, SENS is a synthesis of existing knowledge from the broad mainstream position regarding aging and the diseases of aging: that aging is caused by a stochastic accumulation of damage at the level of cells and protein machinery in and around these cells. SENS is a proposal, based on recent decades of research, as to which of the identified forms of damage and change in old tissues are fundamental - i.e. which are direct byproducts of metabolic operation rather than cascading effects of other fundamental damage. On the development side of the house, SENS pulls together work from many subfields of medical research to show that there are clear and well-defined ways to produce therapies that can repair, reverse, or make irrelevant these fundamental forms of biological damage associated with aging.

(You can read about the various forms of low-level damage that cause aging at the SENS Research Foundation website and elsewhere. This list includes: mitochondrial DNA mutations; buildup of resilient waste products inside and around cells; growing numbers of senescent and other malfunctioning cells; loss of stem cells; and a few others).

Present arguments within the mainstream of aging research are largely over the relative importance of damage type A versus damage type B, and how exactly the extremely complex interaction of damage with metabolism progresses - but not what that damage actually is. A large fraction of modern funding for aging research goes towards building a greater understanding this progression; certainly more than goes towards actually doing anything about it. Here is the thing, however: while understanding the dynamics of damage in aging is very much a work in progress, the damage itself is well known. The research community can accurately enumerate the differences between old tissue and young tissue, or an old cell and a young cell - and it has been a good number of years since anything new was added to that list.

If you can repair the cellular damage that causes aging, it doesn't matter how it happens or how it affects the organism when it's there. This is the important realization for SENS - that much of the ongoing work of the aging research community is largely irrelevant if the goal is to get to human rejuvenation as rapidly as possible. Enough is already known of the likely causes of aging to have a reasonable expectation of being able to produce laboratory demonstrations of rejuvenation in animal models within a decade or two, given large-scale funding.

Expected value drives human endeavor. What path ahead do we expect to produce the greatest gain? In longevity science the investment is concretely measured in money and time, and we might think of the expected value in terms of years of healthy life added by the resulting therapies. The cost of these therapies really isn't much of a factor - all major medical procedures and other therapies tend to converge to similar costs over time, based on their category: consider a surgery versus an infusion versus a course of pills, for example, where it's fairly obvious that the pricing derives from how much skilled labor is involved and how much care the patient requires as a direct result of the process.

On the input side, there are estimates for the cost in time and money to implement SENS therapies for laboratory mice. For the sake of keeping things simple, I'll note that these oscillate around the figures of a billion dollars and ten years for the crash program of fully-funded research. A billion dollars is about the yearly budget of the NIA these days, give or take, which might be a third of all research funding directed towards aging - by some estimates, anyway, though this is a very hard figure to verify in any way. It's by no means certain the that the general one third/two thirds split between government and private research funding extends to aging research.

On the output side, early SENS implementations would be expected to take an old mouse and double its remaining life expectancy - e.g. produce actual rejuvenation, actual repair and reversal of the low-level damage that causes aging, with repeated applications at intervals producing diminishing but still measurable further gains. This is the thing about a rejuvenation therapy that works; you can keep on applying it to sweep up newly accruing damage.

So what other longevity science do we have to compare against? The only large running programs are those that have grown out of the search for calorie restriction mimetic drugs. So there is the past decade or so of research into surtuins, and there is growing interest in mTOR and rapamycin analogs that looks to be more of the same, but slightly better (though that is a low bar to clear).

In the case of sirtuins, money has certainly flowed. Sirtris itself sold for ~$700 million, and it's probably not unreasonable to suggest that a billion dollars has gone into broader sirtuin-related research and development over the past decade. What does the research community have to show for that? Basically nothing other than an increased understanding of some aspects of metabolism relating to calorie restriction and other adaptations that alter life span in response to environmental circumstances. Certainly no mice living longer in widely replicated studies as is the case for mTOR and rapamycin - the sirtuin results and underlying science are still much debated, much in dispute.

The historical ratio of dollars to results for any sort of way to manipulate our metabolism to slow aging is exceedingly poor. The thing is, this ratio shouldn't be expected to get all that much better. Even if marvelously successful, the best possible realistic end result of a drug that slows aging based on what is known today - say something that extracts the best side of mTOR manipulation with none of the side-effects of rapamycin - is a very modest gain in human longevity. It can't greatly repair or reverse existing damage, it can't much help those who are already old become less damaged, it will likely not even be as effective as actual, old-fashioned calorie restriction. The current consensus is that calorie restriction itself is not going to add more than a few years to a human life - though it certainly has impressive health benefits.

(A sidebar: we can hope that one thing that ultimately emerges from all this research is an explanation as to how humans can enjoy such large health benefits from calorie restriction, commensurate with those seen in animals such as mice, without also gaining longer lives to match. But if just eating fewer calories while obtaining good nutrition could make humans reliably live 40% longer, I think that would have been noted at some point in the last few thousand years, or at least certainly in the last few hundred).

From this perspective, traditional drug research turned into longevity science looks like a long, slow slog to nowhere. It keeps people working, but to what end? Not producing significant results in extending human longevity, that's for sure.

The cost of demonstrating that SENS is the right path or the wrong path - i.e. that aging is simply an accumulation of damage, and the many disparate research results making up the SENS vision are largely correct about which forms of change in aged tissue are the fundamental forms of damage that cause aging - is tiny compared to the cost of trying to safely eke out modest reductions in the pace of aging by manipulating metabolism via sirtuins or mTOR.

The end result of implementing SENS is true rejuvenation if aging is caused by damage: actual repair, actual reversal of aging. The end result of spending the same money and time on trying to manipulate metabolism to slow aging can already be observed in sirtuin research, and can reasonably be expected to be much the same the next time around the block with mTOR - it produces new knowledge and little else of concrete use, and even when it does eventually produce a drug candidate, it will likely be the case that you could do better yourself by simply practicing calorie restriction.

The expectation value of SENS is much greater than that of trying to slow aging via the traditional drug discovery and development industry. Ergo the research and development community should be implementing SENS. It conforms to the consensus position on what causes aging, it costs far less than all other proposed interventions into the aging process, and the potential payoff is much greater.


A cell is basically a (very complicated) self-modifying program, encoded in proteins. The same basic outline of human cellular machinery can encompasses everything from germline cells - that seem to be essentially immortal - through to the embryonic stem cells that give rise to all other lineages in the body during early development, through to the hundreds of types of specialized, differentiated cell that run the day to day operations of a living organism.

At some point in the process of creating a new individual, old cells with comparatively heavy damage loads work together to create young cells with comparatively light damage loads (the developing embryo). So there is rejuvenation hidden in there somewhere - possibly occurring in very early embryonic development, prior to the point at which a lot of tissue structure exists to be disrupted by what has to happen.

As the research community is learning to reprogram cells to look and act more like embryonic stem cells or germline cells, producing what are known as induced pluripotent stem cells (or iPS cells), we might not be terribly surprised to see what looks like rejuvenation. Some markers of age in reprogrammed cells and their offspring are removed or diminished in comparison to the cells prior to this reprogramming - though scientists are far from any sort of complete measure of all of the effects, and there are numerous different ways in which cells can be reprogrammed to become more like stem cells. Back in 2010, one group of researchers demonstrated the removal of accumulated mitochondrial damage: take skin cells, obtain induced pluripotent cells from them, then differentiate those iPS cells back into skin cells, and find that the new skin cells lack the mitochondrial damage of the old ones.

This sort of research is encouraging when it comes to the prospects for cell therapies that depend on taking cells from the patient, growing large numbers of them, and then infusing them back into the body. The returning cells are likely going to be of a better quality than those removed.

In this post is a more recent example of some specific markers of age being removed from a cell lineage via the use of induced pluripotency. The researchers focused on blood-generating stem cells, reprogramming them into iPs cells, and then deriving a new lineage of these stem cells that was placed into laboratory animals to assess their function. The find that young blood-generating stem cells and old cells that go through this process are fairly similar, which suggests that it is epigenetic changes that cause observed differences between old and young blood in the wild, and that those changes are somehow smoothed out by the reprogramming process.


The merging of tissue engineering and regenerative medicine (TERM) forms an enormously broad, energetic, and important field of medical research. Here is an excerpt from a review paper published earlier this year and only recently made open access:

The pace of growth is now so fast that it impossible for most of us to keep up with the field as a whole, or even a small subset of it. For example, a TERM search specific to "cartilage" returns more than 450 articles published in 2011 alone, meaning that one would need to read more than one article per day just to stay abreast of this small portion of the TERM terrain.

We found considerable innovation in a number of traditional TERM fields, but also new ideas that are beginning to take hold in emerging focal areas. For instance, in the realm of tissue replacement, we are now seeing not just scaffolds of ever-increasing complexity derived from standard engineering methods, but also complex scaffolds predicated on natural designs (and native tissues themselves, once decellularized). In the broader field of regenerative medicine, we are seeing developmental biology begin to address not just the formation of tissues, but the specific role that endogenous stem cells play in both generative and regenerative processes. Integrating these basic science findings with novel materials that specifically recruit endogenous populations may provide a next wave in smart biomaterials for tissue repair. Likewise, new cell sources, most prominently iPSCs, have come to the fore, making autologous cell-based therapies for any tissue a real possibility.

Finally, our objective screen showed that ours is truly a translational field, and that TERM advances are being reduced to clinical practice at an ever-increasing rate. [Both] the quantitative nature of these outcome measures and levels of evidence in support of these applications are advancing as well. Together, these advances are now beginning to change the lives of small subsets of the population, and in the future, these novel approaches will be able to address a host of diseases and instances of tissue degeneration that were heretofore untreatable.


How much of age-related degeneration stems from lifestyle (secondary aging) versus inherent processes derived from the operation of metabolism (primary aging)? If you become sedentary with age, or pile on the visceral fat, then both of those are going to harm you in ways that overlap with the inherent mechanisms of aging - accelerating the accumulation of damage and dysfunction in and between the cells of your tissues.

The balance of primary versus secondary aging is likely to be different in different tissues. I noticed a few recent papers that look at narrow aspects of muscle aging and find a surprising lack of primary aging, for example. This suggests that many of the observed changes that occur in muscle early in the aging process are driven as much by a lack of exercise - and related matters of lifestyle that have a negative impact on health - as by the known forms of biological damage down at the level of cells and tissues.

You can't exercise your way out of aging to death, but you can certainly make life harder for yourself (and shorter, and more expensive) by failing to remain trim and fit. On the flip side of the coin, however, another set of recent research suggests that the intrinsic primary aging of muscle isn't something that you can do much about through exercise, even while exercise is enormously beneficial for other reasons. That damage of aging will march onward in your muscle tissues, exercised or not.


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!



Friday, March 29, 2013
Metformin, used as a treatment for diabetes, is a weak candidate for a calorie restriction mimetic drug, one that causes some of the same metabolic changes (and thus hopefully health and longevity benefits) as calorie restriction. The evidence for health and longevity benefits actually resulting from this usage is mixed and debatable, however; certainly nowhere near as clear as for, say, rapamycin. Here researchers propose that metfomin's method of action stems in part from suppressing chronic inflammation, which is known to contribute to the progression of age-related frailty and disease: "[Researchers] found that the antidiabetic drug metformin reduces the production of inflammatory cytokines that normally activate the immune system, but if overproduced can lead to pathological inflammation, a condition that both damages tissues in aging and favors tumor growth. Cells normally secrete these inflammatory cytokines when they need to mount an immune response to infection, but chronic production of these same cytokines can also cause cells to age. Such chronic inflammation can be induced, for example by smoking, and old cells are particular proficient at making and releasing cytokines. "We were surprised by our finding that metformin could prevent the production of inflammatory cytokines by old cells. The genes that code for cytokines are normal, but a protein that normally triggers their activation called NF-kB can't reach them in the cell nucleus in metformin treated cells. We also found that metformin does not exert its effects through a pathway commonly thought to mediate its antidiabetic effects. We have suspected that metformin acts in different ways on different pathways to cause effects on aging and cancer. Our studies now point to one mechanism.""

Friday, March 29, 2013
All commonalities in cancer are interesting, as part of the high cost of dealing with cancer is based on the many, many different varieties and the great variability of its biochemistry even between individual tumors. Anything that is common between many types of cancer and between tumors offers a possibility of a lower-cost and broader therapy. The cell surface marker CD47 has shown up of late as a possible commonality, and work continues to see whether a therapy can be built on this: "A decade ago, [researchers] discovered that leukemia cells produce higher levels of a protein called CD47 than do healthy cells. CD47 [is] also displayed on healthy blood cells; it's a marker that blocks the immune system from destroying them as they circulate. Cancers take advantage of this flag to trick the immune system into ignoring them. In the past few years, [researchers] showed that blocking CD47 with an antibody cured some cases of lymphomas and leukemias in mice by stimulating the immune system to recognize the cancer cells as invaders. Now, [researchers] have shown that the CD47-blocking antibody may have a far wider impact than just blood cancers. "What we've shown is that CD47 isn't just important on leukemias and lymphomas. It's on every single human primary tumor that we tested." Moreover, [the scientists] found that cancer cells always had higher levels of CD47 than did healthy cells. How much CD47 a tumor made could predict the survival odds of a patient. To determine whether blocking CD47 was beneficial, the scientists exposed tumor cells to macrophages, a type of immune cell, and anti-CD47 molecules in petri dishes. Without the drug, the macrophages ignored the cancerous cells. But when the CD47 was [blocked], the macrophages engulfed and destroyed cancer cells from all tumor types. Next, the team transplanted human tumors into the feet of mice, where tumors can be easily monitored. When they treated the rodents with anti-CD47, the tumors shrank and did not spread to the rest of the body. In mice given human bladder cancer tumors, for example, 10 of 10 untreated mice had cancer that spread to their lymph nodes. Only one of 10 mice treated with anti-CD47 had a lymph node with signs of cancer. Moreover, the implanted tumor often got smaller after treatment - colon cancers transplanted into the mice shrank to less than one-third of their original size, on average."

Thursday, March 28, 2013
An interesting piece on the use of scaffold materials to guide regrowth in regenerative medicine: "A research group [is] weaving nanoscale nerve-guide scaffolds from a mixture of natural chitosan and an industrial polyester polymer, using a process called electrospinning. The raw materials are dissolved in solvents and placed into a syringe, the needle of which is attached to a high-voltage supply. Charged liquid is then expelled from the needle towards an earthed collector plate. Like a spark between a cloud and a lightning conductor, the liquid stretches out to the collector, and the molecules within it form into a solid but incredibly thin thread. The resulting minuscule fibres accrete into a dense mesh whose texture is similar to that of the body's own connective tissue. In laboratory tests, prototype nerve guides built from this nanomaterial sustained the growth of new neural cells, produced no immune reactions and were much stronger and more flexible than commercial collagen tubes. By adjusting the electrospinning process, the orientation of the nanofibres can be controlled to build scaffolds suitable for cultivating cells that need precise alignment, such as elongated muscle fibres and heart tissue."

Thursday, March 28, 2013
People age at different paces: accumulating damage, dysfunction, and age-related disease comes earlier and faster for some. The current consensus is that some of that is genetic, some epigenetic, but (absent serious genetic abnormalities) most of the difference is due to commonplace lifestyle choices such as smoking, exercise, and calorie intake. "[Researchers have] found new evidence that links faster 'biological' ageing to the risk of developing several age-related diseases - including heart disease, multiple sclerosis and various cancers. "Although heart disease and cancers are more common as one gets older, not everyone gets them - and some people get them at an earlier age. It has been suspected that the occurrence of these diseases may in part be related to some people 'biologically' ageing more quickly than others." The research team measured telomere lengths in over 48,000 individuals and looked at their DNA and identified seven genetic variants that were associated with telomere length. They then asked the question whether these genetic variants also affected risk of various diseases. As DNA cannot be changed by lifestyle or environmental factors, an association of these genetic variants which affect telomere length with a disease also would suggest a causal link between telomere length and that disease. "These are really exciting findings. We had previous evidence that shorter telomere lengths are associated with increased risk of coronary artery disease but were not sure whether this association was causal or not. This research strongly suggests that biological ageing plays an important role in causing coronary artery disease, the commonest cause of death in the world. This provides a novel way of looking at the disease and at least partly explains why some patients develop it early and others don't develop it at all even if they carry other risk factors.""

Wednesday, March 27, 2013
This sort of regenerative medicine research will in the long term help to decipher the signaling produced by different sorts of stem cells in different tissues. Researchers will ultimately remove the need for cell transplants to boost regenerative capabilities and rebuild damaged organs, and produce these effects by controlling existing cell populations: "Amniotic fluid stem (AFS) cells were harvested from rodent amniotic fluid and given to rats with necrotizing enterocolitis (NEC). Other rats with the same condition were given bone marrow stem cells taken from their femurs, or fed as normal with no treatment, to compare the clinical outcomes of different treatments. NEC-affected rats injected with AFS cells showed significantly higher survival rates a week after being treated, compared to the other two groups. Inspection of their intestines, including with micro magnetic resonance imaging (MRI), showed the inflammation to be significantly reduced, with fewer dead cells, greater self-renewal of the gut tissue and better overall intestinal function. While bone marrow stem cells have been known to help reverse colonic damage in irritable bowel disease by regenerating tissue, the beneficial effects from stem cell therapy in NEC appear to work via a different mechanism. Following their injection into the gut, the AFS cells moved into the intestinal villi - the small, finger-like projections that protrude from the lining of the intestinal wall and pass nutrients from the intestine into the blood. However, rather than directly repairing the damaged tissue, the AFS cells appear to have released specific growth factors that acted on progenitor cells in the gut which in turn, reduced the inflammation and triggered the formation of new villi and other tissues. "Stem cells are well known to have anti-inflammatory effects, but this is the first time we have shown that amniotic fluid stem cells can repair damage in the intestines. [Although] amniotic fluid stem cells have a more limited capacity to develop into different cell types than those from the embryo, they nevertheless show promise for many parts of the body including the liver, muscle and nervous system.""

Wednesday, March 27, 2013
A modest step forward on the path towards tissue engineered ovaries: "A proof-of-concept study suggests the possibility of engineering artificial ovaries in the lab to provide a more natural option for hormone replacement therapy for women. [Researchers] report that in the laboratory setting, engineered ovaries showed sustained release of the sex hormones estrogen and progesterone. The project to engineer a bioartificial ovary involves encapsulating ovarian cells inside a thin membrane that allows oxygen and nutrients to enter the capsule, but would prevent the patient from rejecting the cells. With this scenario, functional ovarian tissue from donors could be used to engineer bioartificial ovaries for women with non-functioning ovaries. [Researchers] isolated the two types of endocrine cells found in ovaries (theca and granulosa) from 21-day-old rats. The cells were encapsulated inside materials that are compatible with the body. The scientists evaluated three different ways of arranging the cells inside the capsules. The function of the capsules was then evaluated in the lab by exposing them to follicle-stimulating hormone and luteinizing hormone, two hormones that stimulate ovaries to produce sex hormones. The arrangement of cells that most closely mimicked the natural ovary (layers of cells in a 3-D shape) secreted levels of estrogen that were 10 times higher than other cell arrangements. The capsules also secreted progesterone as well as inhibin and activin, two hormones that interact with the pituitary and hypothalamus and are important to the body's natural system to regulate the production of female sex hormones. "Cells in the multilayer capsules were observed to function in similar fashion to the native ovaries. The secretion of inhibin and activin secretion suggests that these structures could potentially function as an artificial ovary by synchronizing with the body's innate control system.""

Tuesday, March 26, 2013
Autophagy is the collection of housekeeping processes that aim to keep a cell in good shape - free from damaged components and unwanted metabolic byproducts. More autophagy is a good thing, and boosted levels of autophagy seem to be involved in many of the methods found to extend life in laboratory animals. By way of following up on a post from yesterday on apparent damage repair and reversal of some markers of aging in induced pluripotent stem cells (iPSCs), I thought I'd direct your attention to a recent open access paper on the involvement of autophagy in stem cell biology. Perhaps much of the seeming cellular rejuvenation brought about through passing old cell lineages through an induced pluripotent stage has to do with greatly enhanced autophagy: "The implication of autophagy in the maintenance of stemness adds a new layer of control on stem cell activity. Firstly, autophagy may serve as a critical mechanism for the regulation of self-renewal and differentiation. Indeed, stem cells require especially efficient protein turnover to eliminate unwanted proteins, which may otherwise accumulate and impair identity and function. Both autophagy and the ubiquitin-proteasome system (UPS) are important for protein quality control and the maintenance of cellular homeostasis, and they cooperate to regulate cellular aging. Dysfunction or decrease of the stem cell pools is typical of physiological and pathological aging; it would be therefore interesting to determine how these two protein degradation pathways are coordinated in the regulation of stem cell homeostasis, and how the dysregulation of autophagy in stem cells is linked to aging and degenerative diseases. Additionally, the involvement of autophagy in somatic reprogramming suggests a new methodological basis for developing strategies to efficiently generate iPSCs. Finally, increased autophagy may enable cells to overcome the cellular senescence barrier by remodelling the cell cycle machinery or by promoting the turnover of the 'senescent' subcellular architecture. In summary, the study of the interplay between autophagy and cell stemness will not only increase our understanding of the mechanisms and pathways through which autophagy contributes to stem cell maintenance and differentiation, but also enhance our knowledge of the roles of autophagy in human development, aging, and various degenerative diseases. Stem cell rejuvenation and function and large-scale production of high quality transplantable materials through active manipulation of autophagic pathways using small molecules and/or targeted genome-editing technology may be more than a dream."

Tuesday, March 26, 2013
Every cell has its herd of bacteria-like mitochondria, generating fuel for cellular metabolism but also emitting damaging reactive compounds - largely damaging themselves, in fact. Differences in mitochondrial damage resistance are thought to be an important determinant of differences in species life span. Similarly, accumulated mitochondrial damage is most likely an in important contribution to degenerative aging in individuals - making therapies capable of repair a high priority. Here researchers dig in to the degree to which mitochondrial dysfunction appears in aging and various diseases: "Besides their cardinal role in ATP metabolism mitochondria are the main producers of endogenous oxidative radicals. These highly volatile species react with lipids, proteins and nucleic acids in their vicinity. The mitochondrial theory of aging states that an accumulation of damage to these macromolecules throughout the lifetime of an organism leads to cellular decay, loss of tissue homeostasis, and finally to death. Multiple lines of evidence have corroborated this theory and suggested that mitochondrial maintenance may be important in promoting longevity and healthy aging. Indeed, mitochondria have been implicated in most age related diseases such as neurodegeneration, cardiovascular disease and diabetes. If mitochondrial dysfunction is causative in aging, we would expect the accelerated aging disorders to exhibit features of mitochondrial disease. To investigate this, we compiled a database of the clinical parameters seen in mitochondrial diseases, Based on this database we developed extensive bioinformatics tools to dissect whether a disease could be characterized as mitochondrial or not. [Using] these tools we identified a number of diseases as mitochondrially associated that had not previously been considered as mitochondrial. Recently a number of [accelerated aging conditions] have been suggested to have mitochondrial dysfunction and these disorders were also identified by our tools. With the validation of the tools we went on to investigate the mitochondrial involvement in a number of monogenic diseases. Interestingly, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis all showed a substantial mitochondrial involvement. Further, when adding the accelerated aging disorders to the database two groups of progeria appeared; one group associated with chromosomal instability and another group clustered with mitochondrial diseases. Normal aging seemed to associate closer with the mitochondrial group in the clustering algorithm but showed mixed mitochondrial and non-mitochondrial [attributes]. Taken together these findings indicate at least two separate causes of aging, one of them possibly being mitochondrial."

Monday, March 25, 2013
The engineering of replacement organs is progressing. There are ongoing successes with less functional tissue masses such as the bladder wall and trachea, but sights are set on building complex organs such as the heart: "Since a laboratory in North Carolina made a bladder in 1996, scientists have built increasingly more complex organs. There have been five windpipe replacements so far. A London researcher, Alex Seifalian, has transplanted lab-grown tear ducts and an artery into patients. He has made an artificial nose he expects to transplant later this year in a man who lost his nose to skin cancer. Now, with the quest to build a heart, researchers are tackling the most complex organ yet. The payoff could be huge, both medically and financially, because so many people around the world are afflicted with heart disease. Researchers see a multi-billion-dollar market developing for heart parts that could repair diseased hearts and clogged arteries. In additional to the artificial nose, Dr. Seifalian is making cardiovascular body parts. He sees a time when scientists would grow the structures needed for artery bypass procedures instead of taking a vein from another part the body. As part of a clinical trial, Dr. Seifalian plans to transplant a bioengineered coronary artery into a person later this year. Dr. Aviles trained as a cardiologist but became frustrated with the difficulty of treating patients with advanced heart disease. [He] was approached in 2009 by a U.S. scientist, Doris Taylor, who had already grown a beating rat heart in the [lab]. Instead of using a man-made scaffold, Dr. Taylor had used the scaffolding from an actual rat heart as the starting point. Growing a heart is much harder than, say, growing a windpipe, because the heart is so big and has several types of cells, including those that beat, those that form blood vessels, and those that help conduct electrical signals. For a long time, scientists didn't know how to make all the cells grow in the right place and in the right order. Dr. Aviles said he hopes to have a working, lab-made version ready in five or six years, but the regulatory and safety hurdles for putting such an organ in a patient will be high. The most realistic scenario, he said, is that "in about 10 years" his lab will be transplanting heart parts. He and his team already have grown early-stage valves and patches that could be used some day to repair tissue damaged by heart attack."

Monday, March 25, 2013
Registration for the forthcoming SENS6 conference is now open. To get a sense of how this conference series runs and the noteworthy folk who attend, you might take a look at the recorded presentations or list of abstracts from SENS5, held in 2011: "You are cordially invited to participate in the sixth Strategies for Engineered Negligible Senescence (SENS) Conference, which will be held from 3rd - 7th September, 2013 at Queens' College, Cambridge. The purpose of the SENS conference series, like all the SENS initiatives (such as the journal Rejuvenation Research), is to expedite the development of truly effective therapies to postpone and treat human aging by tackling it as an engineering problem: not seeking elusive and probably illusory magic bullets, but instead enumerating the accumulating molecular and cellular changes that eventually kill us and identifying ways to repair - to reverse - those changes, rather than merely to slow down their further accumulation. This broadly defined regenerative medicine - which includes the repair of living cells and extracellular material in situ - applied to damage of aging, is what we refer to as rejuvenation biotechnologies. The meeting will comprise invited talks, short oral presentations of submitted abstracts, and poster sessions. There will be no concurrent sessions. Talks will take place in the Fitzpatrick Lecture Hall. Poster sessions will take place each evening in the conservatory adjacent to the bar. The conference will also feature the traditional punting on the Cam: an hour on the Backs for the faint-hearted, and an afternoon or evening trip to Grantchester for the rest of us."


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