It is good to see some of the larger and better funded life science research communities showing interest in targeting mitochondria - the more people working on this the better, as mitochondria are important in degenerative aging, but there is presently relatively little ongoing research into the practical approaches to mitochondrial repair: "Mitochondria are cytoplasmic organelles responsible for life and death. Extensive evidence from animal models, postmortem brain studies of and clinical studies of aging and neurodegenerative diseases suggests that mitochondrial function is defective in aging and neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Several lines of research suggest that mitochondrial abnormalities, including defects in oxidative phosphorylation, increased accumulation of mitochondrial DNA defects, impaired calcium influx, accumulation of mutant proteins in mitochondria, and mitochondrial membrane potential dissipation are important cellular changes in both early and late-onset neurodegenerative diseases. Further, emerging evidence suggests that structural changes in mitochondria, including increased mitochondrial fragmentation and decreased mitochondrial fusion, are critical factors associated with mitochondrial dysfunction and cell death in aging and neurodegenerative diseases. This paper discusses research that elucidates features of mitochondria that are associated with cellular dysfunction in aging and neurodegenerative diseases and discusses mitochondrial structural and functional changes, and abnormal mitochondrial dynamics in neurodegenerative diseases. It also outlines mitochondria-targeted therapeutics in neurodegenerative diseases."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21470101

The evidence points toward mitochondrial structure and function being very important in the progression of aging within a species and differences in life span between species. Here researchers review some of the mechanisms involved: "Mitochondria are considered major regulators of longevity, although their exact role in aging is not fully understood. Data from different laboratories show a negative correlation between reactive oxygen species (ROS) generated by complex I and lifespan. This suggests that complex I has a central role in the regulation of longevity. Here, we review data that both support and refute the role of complex I as a pacemaker of aging. We include data from our laboratory, where we have manipulated ROS production by the electron transport chain (ETC) in Drosophila melanogaster. The by-pass of complex I increases the lifespan of the fruit fly, but it is not clear if this is caused by a reduction in ROS or by a change in the NAD+ to NADH ratio. We propose that complex I regulates aging through at least two mechanisms: (1) an ROS-dependent mechanism that leads to mitochondrial DNA damage and (2) an ROS-independent mechanism through the control of the NAD+ to NADH ratio. Control of the relative levels of NAD+ and NADH would allow the regulation of (1) glyco- and (2) lipoxidative-damage and (3) the activation of sirtuins." Amongst other things, the NAD+ / NADH ratio determines how much in the way of damaging free radicals a cell exports into the surrounding environment.

Link: http://www.ncbi.nlm.nih.gov/pubmed/21471732

The process of understanding how to manipulate stem cells goes hand in hand with being able to coax them into forming more complex structures, recapitulating the path taken during the original development of the body when young. The state of the art at the present time is crude in comparison to what takes place in our bodies: the only way that researchers can presently obtain complex tissues is by using the extracellular matrix extracted from donor tissue as a guide for new growth. That guidance is as much chemical as structural, which is illustrated in the following recently announced research.

'Retina in a Dish' is the Most Complex Tissue Ever Engineered in the Lab:

Researchers in Japan have grown a retina from mouse embryonic stem cells in a lab, but this isn't just another incremental advance in tissue engineering. Scientists claim their "retina in a dish" is by no small degree the most complex biological tissue yet engineered.

If the breakthrough can be adapted to work with human cells, it could provide a retina that is safe for transplantation into human eyes, providing a potential cure for many kinds of blindness. That's still years away, but in the meantime the lab-grown mouse tissue could provide researchers with a wealth of information on eye diseases and potential treatments for them.

Cultured mouse embryonic stem cells self-organize into a complex retinal structure:

Starting with the culture conditions they had established for retinal differentiation, the researchers added matrix proteins that they hoped would encourage the formation of the more rigid retinal epithelial structures. They then seeded the culture with mouse [embryonic stem] cells. Within a week, the cells began to form small vesicles and differentiate into two different tissue types: Cells on one side of the vesicles formed the mechanically rigid pigment epithelium, while cells on the other side differentiated into a more flexible tissue that folded inward in the shape of an embryonic optic cup - the retina's precursor.

As you can see, researchers remain a long way away from growing a transplant-ready human retina from cells alone - but this is still an important step forward in the path towards producing such a thing. What is learned here will also inform efforts to build the thousand other tissue types we'd like to be able to produce from scratch.

The Methuselah Foundation invests in a variety of companies, and one of them is Silverstone Solutions. Here the Foundation notes a demonstration of the company's product: "In what is the largest single-hospital kidney swap in the history of California, five patients received five kidneys from healthy donors in a marathon series of operations on Friday, April 1st 2011 ... 'Paired donation' is the procedure that makes it possible, a relatively new phenomenon in transplantation surgery that allows for a live kidney going to someone who has a friend or relative willing to donate an organ not compatible for them but a match for someone else. The donor matches one who needs a kidney and that patient's incompatible donor matches someone else and so on, like a chain. ... Imagine that - multiple lives being extended in one fell swoop! This is one of many reasons why Methuselah Foundation has proudly invested in Silverstone Matchmaker, a break-through computer software that makes the pairings possible. It quickly computes the myriad of possible matches in a pool of prospective donors and recipients, minimizing time and effort that the transplant center needs to reach this goal. ... That is why we proudly extend an angel financing arm, funding the development of the bleeding-edge improvements to the Silverstone technology called MatchGrid. This event is in keeping with Methuselah Foundation's strategy of making investments in life-extending technologies that work RIGHT NOW (dangit!) and that also have long term positive implications for general life extension in the tissue engineering realm. Our long term vision for this technology? We hope that its massive and super performance data management system will eventually play a role in the an envisioned 'Postscript' language that can send printing instructions for creating new tissues and eventually organs to be used by tissue printers such as Organovo's sci-fi worthy 3D tissue printer, another founding angel investment by you, the donors of Methuselah Foundation."

http://blog.methuselahfoundation.org/2011/04/hot_dog_a_record-breaking_5-transplant_kidney_swap.html

The Methuselah Foundation invests in a variety of companies, and one of them is Silverstone Solutions. Here the Foundation notes a demonstration of the company's product: "In what is the largest single-hospital kidney swap in the history of California, five patients received five kidneys from healthy donors in a marathon series of operations on Friday, April 1st 2011 ... 'Paired donation' is the procedure that makes it possible, a relatively new phenomenon in transplantation surgery that allows for a live kidney going to someone who has a friend or relative willing to donate an organ not compatible for them but a match for someone else. The donor matches one who needs a kidney and that patient's incompatible donor matches someone else and so on, like a chain. ... Imagine that - multiple lives being extended in one fell swoop! This is one of many reasons why Methuselah Foundation has proudly invested in Silverstone Matchmaker, a break-through computer software that makes the pairings possible. It quickly computes the myriad of possible matches in a pool of prospective donors and recipients, minimizing time and effort that the transplant center needs to reach this goal. ... That is why we proudly extend an angel financing arm, funding the development of the bleeding-edge improvements to the Silverstone technology called MatchGrid. This event is in keeping with Methuselah Foundation's strategy of making investments in life-extending technologies that work RIGHT NOW (dangit!) and that also have long term positive implications for general life extension in the tissue engineering realm. Our long term vision for this technology? We hope that its massive and super performance data management system will eventually play a role in the an envisioned 'Postscript' language that can send printing instructions for creating new tissues and eventually organs to be used by tissue printers such as Organovo's sci-fi worthy 3D tissue printer, another founding angel investment by you, the donors of Methuselah Foundation."

http://blog.methuselahfoundation.org/2011/04/hot_dog_a_record-breaking_5-transplant_kidney_swap.html

Researchers continue to investigate how to replicate the limb regeneration found in lower animals: "Move over, newts and salamanders. The mouse may join you as the only animal that can re-grow their own severed limbs. Researchers are reporting that a simple chemical cocktail can coax mouse muscle fibers to become the kinds of cells found in the first stages of a regenerating limb. Their study, the first demonstration that mammal muscle can be turned into the biological raw material for a new limb ... their 'relatively simple, gentle, and reversible' methods for creating the early stages of limb regeneration in mouse cells 'have implications for both regenerative medicine and stem cell biology.' In the future, they suggest, the chemicals they use could speed wound healing by providing new cells at the injured site before the wound closes or becomes infected. Their methods might also shed light on new ways to switch adult cells into the all-purpose, so-called 'pluripotent' stem cells with the potential for growing into any type of tissue in the body. The scientists describe the chemical cocktail that they developed and used to turn mouse muscle fibers into muscle cells. [They] then converted the muscle cells turned into fat and bone cells. Those transformations were remarkably similar to the initial processes that occur in the tissue of newts and salamanders that is starting to regrow severed limbs."

Link: http://www.eurekalert.org/pub_releases/2011-04/acs-scc040611.php

You might recall that the Immortality Institute raised funds for a test of laser ablation of lipofuscin, to run on nematode worms using commercially available laser equipment:

The good news for today is that the longevity science grassroots centered at the Immortality Institute have successfully raised $8,000 to fund research into laser ablation of lipofuscin. Those funds will be matched up to $16,000 at the SENS Foundation and put towards work on a method of eliminating one form of damaging metabolic byproducts that build up with age.

Lipofuscin is the name given to a collection of various waste products of metabolism that are hard for the body to break down. They build up inside cells, collecting in the recycling mechanisms of lysosomes and causing cellular housekeeping to progressively fail over time. Ways to safely break down lipofuscin are very much required as a part of the envisaged package of future rejuvenation biotechnology that can prevent and reverse aging.

One proposed methodology for tackling lipofuscin is the use of pulsed laser light targeted at very specific molecules and molecular bonds: in theory, it should be possible to significantly impact lipofuscin levels without harming the cells that contain this gunk. Whether this is the case in practice remains to be seen, but it is an approach well worth testing: after all, lasers are already routinely used in dermatology to achieve conceptually similar goals, and the cost of this test is minimal in the grand scheme of things. Hence the laser ablation project funded by forward-looking donor and organized by the Immortality Institute.

You'll find recent updates on the state of the laser ablation test in the Longecity thread for the project:

Here is the basic agenda for the remainder of the project:

1) Test the effect of 8ns pulses on worm lifespan, at many different intensities. ... The beam coming straight out of the laser has terrific coherence and a nice tophat profile, which although it is 8ns, which is a little harsh, it is wonderfully consistent, great at destroying pigments, and we can rest assured that all worms on the slide are getting the exact same exposure every time.

2) Examine effect on worm activity/livelihood. Since the worms grow distinctively and progressively less active in the 2nd half of their life, this can be used to roughly assess quality of life changes; i.e. if worms are all dying at the same time, but at 75% lifespan, laser-treated groups are still quite active, this could be seen as a definite extension of useful lifespan.

3) Examine changes in pigmentation, if any. I may even be able to rig up a crude blacklight setup and get some fluorescence going. Or we could lop two months of the end of the 8-month project and buy a basic fluorescence scope with the extra $2500

...

4) Assess the effect of laser treatment on a more long-lived strain of worms (such as DAF-16 mutants), as well as the wild-type. This could provide useful clues as to what is going on, whichever way the results go.

...

It's still taking awhile to breed more DA1116 worms. I can see how this is going to go - things are going to stretch out a bit, partly due to my schedule and partly due to using long-lived worms, and the nature of lifespan experiments in general. Therefore I propose using experiments as milestones instead of sticking to a fixed weekly or monthly schedule. Thus the project will span at least 8 complete lifespan experiments, regardless of how long it takes to complete them. The remaining 'monthly' salary and expense checks could be sent at the start of experiments 3, 5 and 7 - which will doubtless end up being more than one month apart. This definitely seems more appropriate to me - that way all of our gracious donors get the same amount of science for their money, regardless of how long it takes.

The fluorescence scope may or may not be purchased for this project, depending on how our financial situation pans out on this end. It may end up being budgeted as part of a future project proposal instead; but we can cross that bridge when we get there.

I'll let everyone know as soon as the worm zapping begins.

One of the Immortality Institute volunteers visited the lab recently, and so you'll find photographs of the equipment, work area, and researcher in the thread to go along with the updates.

By way of a reminder, the Institute continues to raise funding for their next project, an investigation of microglia transplantation as a therapy for age-related neurodegeneration. $5,500 of the needed $8,000 has been raised, and futher donations are very welcome. Every dollar donated will be matched by an additional dollar from the Institute and its sponsors, so that the completed fundraiser will send $16,000 to the laboratory that will carry out the research:

Cognitive functions of the brain decline with age. One of the protective cell types in the brain are called microglia cells. However, these microglia cells also loose function with age. Our aim is to replace non-functional microglia [in mice] with new and young microglia cells derived from adult stem cells.

...

The full PDF format research proposal is available: the work will be carried out by a graduate research assistant and will cost $16,000. This is the essence of our present era of biotechnology: a task that would have occupied a whole laboratory and its equipment in the 1980s, and cost a great deal of money if it was even possible at all, is now something that a skilled graduate-level life scientist can organize and run himself within an established lab.

You might recall that the Immortality Institute raised funds for a test of laser ablation of lipofuscin, to run on nematode worms using commercially available laser equipment:

The good news for today is that the longevity science grassroots centered at the Immortality Institute have successfully raised $8,000 to fund research into laser ablation of lipofuscin. Those funds will be matched up to $16,000 at the SENS Foundation and put towards work on a method of eliminating one form of damaging metabolic byproducts that build up with age.

Lipofuscin is the name given to a collection of various waste products of metabolism that are hard for the body to break down. They build up inside cells, collecting in the recycling mechanisms of lysosomes and causing cellular housekeeping to progressively fail over time. Ways to safely break down lipofuscin are very much required as a part of the envisaged package of future rejuvenation biotechnology that can prevent and reverse aging.

One proposed methodology for tackling lipofuscin is the use of pulsed laser light targeted at very specific molecules and molecular bonds: in theory, it should be possible to significantly impact lipofuscin levels without harming the cells that contain this gunk. Whether this is the case in practice remains to be seen, but it is an approach well worth testing: after all, lasers are already routinely used in dermatology to achieve conceptually similar goals, and the cost of this test is minimal in the grand scheme of things. Hence the laser ablation project funded by forward-looking donor and organized by the Immortality Institute.

You'll find recent updates on the state of the laser ablation test in the Longecity thread for the project:

Here is the basic agenda for the remainder of the project:

1) Test the effect of 8ns pulses on worm lifespan, at many different intensities. ... The beam coming straight out of the laser has terrific coherence and a nice tophat profile, which although it is 8ns, which is a little harsh, it is wonderfully consistent, great at destroying pigments, and we can rest assured that all worms on the slide are getting the exact same exposure every time.

2) Examine effect on worm activity/livelihood. Since the worms grow distinctively and progressively less active in the 2nd half of their life, this can be used to roughly assess quality of life changes; i.e. if worms are all dying at the same time, but at 75% lifespan, laser-treated groups are still quite active, this could be seen as a definite extension of useful lifespan.

3) Examine changes in pigmentation, if any. I may even be able to rig up a crude blacklight setup and get some fluorescence going. Or we could lop two months of the end of the 8-month project and buy a basic fluorescence scope with the extra $2500

...

4) Assess the effect of laser treatment on a more long-lived strain of worms (such as DAF-16 mutants), as well as the wild-type. This could provide useful clues as to what is going on, whichever way the results go.

...

It's still taking awhile to breed more DA1116 worms. I can see how this is going to go - things are going to stretch out a bit, partly due to my schedule and partly due to using long-lived worms, and the nature of lifespan experiments in general. Therefore I propose using experiments as milestones instead of sticking to a fixed weekly or monthly schedule. Thus the project will span at least 8 complete lifespan experiments, regardless of how long it takes to complete them. The remaining 'monthly' salary and expense checks could be sent at the start of experiments 3, 5 and 7 - which will doubtless end up being more than one month apart. This definitely seems more appropriate to me - that way all of our gracious donors get the same amount of science for their money, regardless of how long it takes.

The fluorescence scope may or may not be purchased for this project, depending on how our financial situation pans out on this end. It may end up being budgeted as part of a future project proposal instead; but we can cross that bridge when we get there.

I'll let everyone know as soon as the worm zapping begins.

One of the Immortality Institute volunteers visited the lab recently, and so you'll find photographs of the equipment, work area, and researcher in the thread to go along with the updates.

By way of a reminder, the Institute continues to raise funding for their next project, an investigation of microglia transplantation as a therapy for age-related neurodegeneration. $5,500 of the needed $8,000 has been raised, and futher donations are very welcome. Every dollar donated will be matched by an additional dollar from the Institute and its sponsors, so that the completed fundraiser will send $16,000 to the laboratory that will carry out the research:

Cognitive functions of the brain decline with age. One of the protective cell types in the brain are called microglia cells. However, these microglia cells also loose function with age. Our aim is to replace non-functional microglia [in mice] with new and young microglia cells derived from adult stem cells.

...

The full PDF format research proposal is available: the work will be carried out by a graduate research assistant and will cost $16,000. This is the essence of our present era of biotechnology: a task that would have occupied a whole laboratory and its equipment in the 1980s, and cost a great deal of money if it was even possible at all, is now something that a skilled graduate-level life scientist can organize and run himself within an established lab.

Researchers have demonstrated that "damaged muscle tissues treated with satellite cells in a special degradable hydrogel showed satisfactory regeneration and muscle activity. Muscle activity in repaired muscle in a mouse model was comparable with untreated muscles. ... Satellite cells (SCs), freshly isolated or transplanted within their niche, are presently considered the best source for muscle regeneration. They are located around existing muscles. Hence, a patient's own cells can be used, from a muscle biopsy. ... A key issue for regeneration is how cells grow as a structure, as they usually require some form of framework. A hard framework would impede muscle growth and muscle cell penetration. The hydrogel, by contrast, provides a supportive structural skeleton but degrades quickly as muscle tissue returns and the support becomes unnecessary. The gel is initially liquid, hardens in place under UV light, and is easily penetrated by muscle cells. ... This is using the patient's own cells, without any lengthy culturing process, which means we could take a biopsy, produce the cells in a couple of hours, and implant them where needed - it can be done in theatre as one process. Using the patient's own cells eliminates any tissue rejection. ... The focus for initial clinical research in humans will be relatively small muscles at first, like deformities in the face and palate, or in the hand. It will be technically more demanding to grow larger muscles with more structure, which would require their own nerves and blood supply."

Link: http://www.ucl.ac.uk/news/news-articles/1103/31031101

The Methuselah Generation is a documentary film in progress, far enough along that the filmmaker is putting out early versions: "Is aging a disease that can be cured? Is it possible to live forever? Even if we could, should we? The Methuselah Generation (working title) is a 3D verite documentary about the science and philosophy of Life Extension - the scientific hypothesis that individuals may be capable of extending human life beyond anything humans have yet imagined. The story will follow a select few individuals at the forefront of this movement as well as those skeptical and antagonistic toward the goals of life extension. The film will follow five protagonists as they progress with their movement to change humanity. Through intimate interviews, observational shooting and provocative imagery, this character-based 3D documentary will explore the big philosophical ideas of Life Extension, while also examining the scientific feasibility - the film will explore the what, how and (most significantly) the WHY of long-lived humans."

Link: http://davidalvarado.info/le.html

The evolutionary view of cancer and aging is that these end points stand in opposition: complex organisms such as mammals evolve to some point of balance between risk of cancer and certainty of accelerated aging. This happens because the mechanisms that suppress cancer also inhibit the necessary regenerative capacity to maintain tissue function: it's largely a matter of how free cells are to divide and multiply, taking into account the increasing levels of damage and mutation with age - which increase the chance of a cancer developing.

In research focused on this balance between aging and cancer, two genes - and the proteins they produce - are especially important: p53 and p16. Both can suppress cancer, but at the cost of accelerated aging:

• On p53 and Aging
• Understanding a Tumor Suppression Gene

p16 has been particularly interesting of late because it appears to be a plausible candidate for the cancer immunity observed in naked mole rats:

the mole rat's cells express a gene called p16 that makes the cells 'claustrophobic,' stopping the cells' proliferation when too many of them crowd together, cutting off runaway growth before it can start. The effect of p16 is so pronounced that when researchers mutated the cells to induce a tumor, the cells' growth barely changed

Unfortunately, as recent research illustrates, making use of this knowledge isn't as easy as just ramping up p16 gene expression in other mammal species:

"I didn't anticipate that increased production of the p16 tumor suppressor protein would so readily promote aging," says Enders, who led the study. "The p16 protein has been previously associated with aging, and we know its expression increases during late stages of aging. But the idea that its expression would be sufficient to generate features of aging was surprising."

Although scientists know that loss of p16 is associated with numerous human tumors, they know much less about the function of p16 in normal cells and tissues. To explore this, Enders' team engineered a strain of mice that enables them to control p16 expression in various tissues and at various times in an animal's lifespan. They quickly found that turning on p16 blocked cell proliferation in normal tissues.

The implications of blocked cell proliferation emerged when they expressed p16 in animals that were not yet fully mature. "They developed features of premature aging," Enders says. "To my knowledge, this is the first model that induces striking characteristics of premature aging where there is no macromolecular damage. The premature aging appears to be the result of blocking cell proliferation."

In this respect, p16 is very similar in behavior to p53. But that in fact means that there is great promise inherent in p16 research: a few years ago, Spanish researchers engineered their way around the aging-cancer balance in mice for p53, producing mice that suffered less cancer and lived 50% longer than normal. Trying a similar approach with p16 sounds very plausible. It is also possible that their work is analogous to the biology of naked mole-rats, animals that manage to live vastly longer than the members of other similarly sized rodent species, and this despite their evolved usage of p16 and apparently complete immunity to cancer. Equally, mole-rats might exhibit yet another completely different configuration of mammalian biology - one that it may soon be possible to reverse engineer and test in mice.

Answers to this sort of speculation still lie in the near future, but research into the biochemistry of p16 and p53 is worth keeping an eye on. Few other methodologies can claim to have extended healthy life in mice by as much as that mentioned above, and, furthermore, somewhere in the biology of these species lies a way to simply turn off cancer.

Allow me to point you to the results of a long-running study on metabolic rate and mortality:

Higher metabolic rates increase free radical formation, which may accelerate aging and lead to early mortality. ... Our objective was to determine whether higher metabolic rates measured by two different methods predict early natural mortality in humans. ... Twenty-four-hour energy expenditure (24EE) was measured in 508 individuals, resting metabolic rate (RMR) was measured in 384 individuals.

The study ran with hundreds of participants over more than twenty years and concluded that there is a good correlation between these measures of metabolic rate and risk of death:

For each 100-kcal/24 h increase in EE, the risk of natural mortality increased by 1.29 in the 24EE group and by 1.25 in the RMR group, after adjustment for age, sex, and body weight in proportional hazard analyses.

The higher your resting metabolic rate, the greater your expected chance of death by aging or disease sometime soon - a cheerful prospect. My first thought was that these measurements should reflect levels of physical fitness achieved through exercise, which we know has a strong effect on mortality, but apparently not:

Studies published in 1992 and 1997 indicate that the level of aerobic fitness of an individual does not have any correlation with the level of resting metabolism. Both studies find that aerobic fitness levels do not improve the predictive power of fat free mass for resting metabolic rate.

There's a lesson there concerning the practice of quickly leaping to what might seem to be sensible conclusions. My slower second thought involved calorie intake: even mild levels of calorie restriction have measurable impacts on health in humans and on longevity in lower animals. Possibly also on longevity in humans, though that study will likely never be undertaken - if started tomorrow, by the time it was even half-way complete we'd be well into the era of rejuvenation biotechnology, making the whole exercise rather pointless.

In any case, the practice of calorie restriction does lower resting metabolic rate, and does so across a range of species: stick insects, rhesus monkeys, and humans, to pick a few. So it seems reasonable to theorize that differences in mortality seen in the study quoted above are reflections of the natural variance of calorie intake amongst the participants, and the biochemical - and existential - consequences of lower versus higher calorie diets.

The liver has the greatest capacity for regeneration amongst human organs - but there's always room for improvement. Here, cancer researchers incidentally uncover a potential mechanism to safely boost regenerative capacity: "During chronic liver damage repetitive waves of hepatocyte cell death and compensatory proliferation take place, eventually culminating in chronic liver failure and often in the development of hepatocellular carcinoma (HCC). A misregulated regenerative response to chronic liver injury may represent the base for development of HCC. Therefore, a more detailed understanding of signaling pathways involved in proliferation control of hepatocytes not only holds the great promise of informing new therapies to increase the hepatic regenerative potential but also to deduce new strategies for the treatment of HCC. We have established a unique system to perform in vivo RNAi screens to genetically dissect cellular signaling networks regulating hepatocyte proliferation during chronic liver damage. ... we identified shRNAs which showed strong enrichment during regeneration, therefore pinpointing new regulators of liver regeneration. Our top scoring candidate represents a kinase, which is accessible to pharmacological inhibition. Functional in vivo validation studies show that stable knockdown of the candidate gene by different shRNAs can significantly increase the repopulation efficiency of mouse hepatocytes and also increases the regenerative capacity of chronically damaged mouse livers. Despite the fact that some human HCCs show focal deletion of the candidate gene, a therapeutic window for regenerative therapy exists, as mice stably repopulated with shRNAs against the candidate did not develop liver tumors."

Link: http://www1.easl.eu/easl2011/program/Orals/261.htm

Type 2 diabetes is a lifestyle disease, avoidable for vast majority of people. If you overeat, become fat, and live a sedentary life then the odds are good you'll develop the condition, or at least its precursor, metabolic syndrome. The cost of this neglect of health basics is measurable: "Middle-aged adults with diabetes are much more likely to develop age-related conditions than their counterparts who don't have diabetes, according to a new study ... Adults between 51 and 70 with diabetes developed age-related ailments like cognitive impairment, incontinence, falls, dizziness, vision impairment and pain at a faster rate than those without diabetes, the study found. ... Our findings suggest that middle age adults with diabetes start to accumulate these age-related problems. Because diabetes affects multiple organ systems, it has the potential to contribute significantly to the development of a number of issues that we associate with aging ... For adults aged 51-60 with diabetes, the odds of developing new geriatric conditions were nearly double those of their counterparts who didn't have diabetes, the researchers found. By the time people with and without diabetes reach 80, the overall effects of aging and impact of other diseases start to reduce the disparities between the two groups. ... The findings suggest that adults with diabetes should be monitored for the development of these conditions beginning at a younger age than we previously thought." Though of course your odds of making it to 80 to be compared to your healthier cohorts are not as good if you're diabetic. So don't get fat, don't stay fat, and exercise sounds like good advice.

Link: http://www.eurekalert.org/pub_releases/2011-03/uomh-acd033111.php

If you can have a range of single nucleotide polymorphisms and other quirks of your DNA analyzed by mail and presented via an online service, then why not the same for the length of your telomeres?

Telomeres - the terminal caps of chromosomes - become shorter as individuals age, and there is much interest in determining what causes telomere attrition since this process may play a role in biological aging. The leading hypothesis is that telomere attrition is due to inflammation, exposure to infectious agents, and other types of oxidative stress, which damage telomeres and impair their repair mechanisms. Several lines of evidence support this hypothesis, including observational findings that people exposed to infectious diseases have shorter telomeres.

At least two nascent companies presently aim to commercialize telomere measurement technologies: Telomere Health and Life Length were recently featured in Scientific American:

"Knowing whether our telomeres are a normal length or not for a given chronological age will give us an indication of our health status and of our physiological 'age' even before diseases appear," says Maria A. Blasco, who heads the Telomeres and Telomerase Group at the Spanish National Cancer Research Center and who co-founded the company Life Length in September. Telomere research pioneer Calvin B. Harley, who co-founded Telome Health last spring with Nobel laureate Elizabeth H. Blackburn, considers telomere length "probably the best single measure of our integrated genetics, previous lifestyle and environmental exposures." Beginning as early as this spring, the companies will offer telomere-measurement tests to research centers and companies studying the role of telomeres in aging and disease; the general public may have access by the fall through doctors and laboratories, perhaps even directly.

I think that these initiatives are not so interesting in and of themselves, but should be considered as part of a powerful trend now underway. The marketplace for personal biochemical information supplied on demand, via mail and internet, will only grow as the underlying technologies become cheaper, more reliable, and possible to run at scale. One very desirable next stage in the evolution of this marketplace is to do away with the mail portion - the need to send samples in envelopes to a central processing location. The tools of analysis are becoming ever cheaper, and it won't be too many more years before it is cost-effective for most people in the developed world to produce raw data from their own biochemistries with desktop devices at home. The results will be sent over the network to be processed, analyzed, and matched against sophisticated databases owned by for-pay subscription services.

This vision will of course be fought against tooth and nail by the myriad entrenched interests in the command and control style medical systems of the Western nations - those who benefit from medical regulation at the expense of progress. These interests can't stop the internet, however, and nor can they regulate devices that connect to encrypted services outside the US. Distributed medicine, in which a great deal of the process of managing diagnosis and data collection rests with ordinary people, is the inevitable end result of falling costs in biotechnology and communication technologies. This is a good thing, and the sooner all opposed give up and go home, the better.

A recent review: "The function of adult tissue-specific stem cells declines with age, which may contribute to the physiological decline in tissue homeostasis and the increased risk of neoplasm during aging. Old stem cells can be 'rejuvenated' by environmental stimuli in some cases, raising the possibility that a subset of age-dependent stem cell changes is regulated by reversible mechanisms. Epigenetic regulators are good candidates for such mechanisms, as they provide a versatile checkpoint to mediate plastic changes in gene expression and have recently been found to control organismal longevity. Here, we review the importance of chromatin regulation in adult stem cell compartments. We particularly focus on the roles of chromatin-modifying complexes and transcription factors that directly impact chromatin in aging stem cells. Understanding the regulation of chromatin states in adult stem cells is likely to have important implications for identifying avenues to maintain the homeostatic balance between sustained function and neoplastic transformation of aging."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21441951