Enhanced regeneration can result from introducing new stem cells into a patient, and this effect is the basis for a very broad range of first generation transplant therapies. In most cases the benefit doesn't result from the transplanted stem cells setting forth to create replacement cells for damaged tissue. Instead it is caused by chemical signals produced by the transplanted cells: these signals spur native cell populations to take action. So naturally the next step here is for researchers to gain a good enough understanding of stem cell signals to remove the need for cell transplants, replacing them with a therapy based on introducing the signal molecules directly.

It's very hard to say how rapidly this line of research will progress in comparison to the ongoing development of therapies that involve cells, a field in full swing. But in the long term it seems likely that directly adjusting the state and behavior of a patient's native cells will win out over indirect methods. Using the signals may just be another indirect method to be replaced by something better down the line, such as targeted epigenetic engineering that reprograms specific cell populations without going through any of the evolved signal paths.

But that is a way from here, as the use of stem cells in therapy is still two decades away from its peak usage and effectiveness - if we want to take the standard view of fifty year cycles in broad technologies, waxing to full effectiveness and then waning as they are replaced by something better. The cycle may run faster this century: we'll see whether that is the case or not, something that is determined by the degree to which the timing depends on human organization versus technological capacity. The former isn't speeding up, while the latter is.

Meanwhile, here is an open access paper that illustrates the way in which scientists are presently looking at stem cell signals. The research community is clearly on the way towards a range of these signal compounds repackaged and repurposed as drug candidates to induce exceptional regeneration. I expect that line of development will be well underway by the early 2020s.

hESC-secreted proteins can be enriched for multiple regenerative therapies by heparin-binding

Tissue regeneration and maintenance dramatically and invariably decline with age, eventually causing failure of multiple organ systems in all mammals. In muscle, the loss of tissue regeneration with age is thought to be imposed by signaling changes in the satellite stem cell niche, and interestingly, the aging of stem cell niches is to some extent similar between muscle, brain, blood, and other tissues. Our previous work found that human embryonic stem cells (hESCs) produce soluble secreted molecules that can counteract the age-imposed inhibition of muscle regeneration, an "anti-aging" activity that is lost when the hESCs differentiate.

Numerous mitogenic proteins are expressed by hESCs and are known to act through [key regulatory signaling pathways] implicated in the control of adult tissue regeneration. The precise identity of the pro-myogenic factors that are secreted by hESCs and the molecular mechanism of their action in muscle stem and progenitor cells is still work in progress; however, the effects of one of these molecules, FGF-2, was studied here in detail. FGF-2 is known to be secreted by hESCs and is also contained in the growth/expansion medium of embryonic stem cells.

This work builds upon our findings that proteins secreted by hESCs exhibit pro-regenerative activity, and determines that hESC-conditioned medium robustly enhances the proliferation of both muscle and neural progenitor cells. Importantly, this work establishes that it is the proteins that bind heparin which are responsible for the pro-myogenic effects of hESC-conditioned medium, and indicates that this strategy is suitable for enriching the potentially therapeutic factors. Additionally, this work shows that hESC-secreted proteins act independently of the mitogen FGF-2, and suggests that FGF-2 is unlikely to be a pro-aging molecule in the physiological decline of old muscle repair. Moreover, hESC-secreted factors improve the viability of human cortical neurons in an Alzheimer's disease (AD) model, suggesting that these factors can enhance the maintenance and regeneration of multiple tissues in the aging body.

You'll find more on the role of FGF-2 regarding stem cells and aging back in last year's archives. The authors quoted above suggest that past work on FGF-2 can't be the whole picture, based on their observations, and something more complex is taking place - which is the usual story in life science research. Nothing is ever simple.

• Commentary on FGF Signaling and Stem Cell Aging
• Inhibiting FGF2 in Mice Slows Muscle Stem Cell Decline With Age

Source:
http://www.fightaging.org/archives/2013/05/considering-the-regenerative-signals-emitted-by-transplanted-stem-cells.php

New approaches to electromechanical artificial hearts involve the replacement of some portions of the machine with tissue, such as the cow heart tissue used in this case. The end result is a more durable apparatus that better interfaces with the body, though it's still the case that artificial heart technology cannot replace a biological heart for the long term:

A new kind of artificial heart that combines synthetic and biological materials as well as sensors and software to detect a patient's level of exertion and adjust output accordingly is to be tested in patients at four cardiac surgery centers in Europe and the Middle East. If the "bioprosthetic" device, made by the Paris-based Carmat, proves to be safe and effective, it could be given to patients waiting for a heart transplant.

In Carmat's design, two chambers are each divided by a membrane that holds hydraulic fluid on one side. A motorized pump moves hydraulic fluid in and out of the chambers, and that fluid causes the membrane to move; blood flows through the other side of each membrane. The blood-facing side of the membrane is made of tissue obtained from a sac that surrounds a cow's heart, to make the device more biocompatible. "The idea was to develop an artificial heart in which the moving parts that are in contact with blood are made of tissue that is [better suited] for the biological environment."

That could make patients less reliant on anti-coagulation medications. The Carmat device also uses valves made from cow heart tissue and has sensors to detect increased pressure within the device. That information is sent to an internal control system that can adjust the flow rate in response to increased demand, such as when a patient is exercising.

Link: http://www.technologyreview.com/news/515021/the-latest-artificial-heart-part-cow-part-machine/

Source:
http://www.fightaging.org/archives/2013/05/a-bioprosthetic-heart.php

Some age-related conditions are greatly impacted by exercise, and a sedentary lifestyle is one of the factors raising the risk of suffering these conditions. Type 2 diabetes is the best known of these, a lifestyle disease that you can actually exercise and diet your way out of if you work at it hard enough. Peripheral artery disease isn't so escapable, being a later stage in the process of deterioration, but exercise is still beneficial to a point comparable to other options for treatment:

Peripheral arterial disease (PAD) is a common vascular disease that reduces blood flow capacity to the legs of patients. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility, and in advanced cases leads to frank ischemia with pain at rest. It is estimated that 12 to 15 million people in the United States are diagnosed with PAD, with a much larger population that is undiagnosed.

The presence of PAD predicts a 50% to 1500% increase in morbidity and mortality, depending on severity. Treatment of patients with PAD is limited to modification of cardiovascular disease risk factors, pharmacological intervention, surgery, and exercise therapy. Extended exercise programs that involve walking approximately five times per week, at a significant intensity that requires frequent rest periods, are most significant.

Preclinical studies and virtually all clinical trials demonstrate the benefits of exercise therapy, including improved walking tolerance, modified inflammatory/hemostatic markers, enhanced vasoresponsiveness, adaptations within the limb (angiogenesis, arteriogenesis, and mitochondrial synthesis) that enhance oxygen delivery and metabolic responses, potentially delayed progression of the disease, enhanced quality of life indices, and extended longevity. [The] benefits are so compelling that exercise prescription should be an essential option presented to patients with PAD in the absence of contraindications. Obviously, selecting for a lifestyle pattern that includes enhanced physical activity prior to the advance of PAD limitations is the most desirable and beneficial.

Is there a lesson here? Yes: exercise regularly. Don't be sedentary.

Link: http://www.ncbi.nlm.nih.gov/pubmed/23720270

Source:
http://www.fightaging.org/archives/2013/05/exercise-versus-peripheral-artery-disease.php

Billionaires are just like you and I, but with deeper pockets. They will age and die on the same schedule as the rest of us, as future life span is almost entirely determined by the pace of progress in medical science and the availability of modern medicine is very flat. Within a few years of any new medical technology arriving in the clinic it settles to a price that can be widely afforded. If you're sixty and sitting on your retirement fund then there's very little in the way of medicine that a billionaire could afford but you can't. The billionaire can afford a dedicated hospital with new wall murals, but the therapies are exactly the same as those you'd buy for yourself: a stem cell transplant or infusion of enzymes doesn't care about the size of your bank balance.

Here is another way in which billionaires are just like the rest of us: very few of them care enough about aging to death to do anything about it. Or they don't believe that anything can be done, or they are not up to speed with the present state of longevity science and the potential of SENS-style rejuvenation biotechnology, or any one of the other reasons offered up whenever people's attitudes towards aging are discussed.

Just as a small fraction of the public care enough about aging to do something about it - ranging from donating a little money or time to organizations like the Methuselah Foundation or SENS Research Foundation all the way up to quitting work, going back to school, and becoming a researcher - a small number of billionaires also take steps. Again, these range from modest donations through to the hard right turn in life to take a different path and focus fully on the problem of aging. Unfortunately of these folk only one is a patron for SENS, while the others are focus on different areas that are, ultimately, not particularly relevant to our future longevity for one reason or another. Such is life.

So you might say that SENS, the research program we'd like to see gain a vocal zealot willing to spend hundreds of millions of dollars, is bracketed by billionaires. Interested billionaires in fields just off to the left, interested billionaires in fields just off to the right. The optimistic view is that yes, it's just a matter of time until someone is convinced and takes the plunge - because, clearly, some people are thinking along parallel lines and thus we should expect there to be more in the future.

Larry Ellison

Of all the mentioned billionaires, Ellison comes closest to the right direction, but in many ways he's the least interested. He established the Ellison Medical Foundation in the 1990s to explore aging - not because longevity is a passion, but rather because aging research is a good source of intellectual and organizational challenges in the field of molecular biology. Molecular biology was the object, and aging research the happenstance outlet. So the end result is effectively an extension of the National Institute on Aging, and therefore focused on work that has little relevance to extending life. The majority of NIA-funded research is a matter of investigation, not intervention.

Peter Thiel

Thiel has funneled some millions of dollars into SENS research and is to be commended for doing so in a very public way at a time when you could still be ridiculed for it. He is also engaged in producing a broader environment of philanthropy within the networks he can reach with the aim of promoting greater investment and interest. SENS is just one of many radical projects he backs, however, a single part of the large jigsaw puzzle that is Thiel's attempt to influence the building of a better future.

David Murdock

Murdock's interest with longevity extends only so far as its intersection with diet and clean living. He has founded a research institute, the North Carolina Research Campus - and I think that if you manage to create a legacy of scientific research then it's hard to say you went far wrong in life. The focus here is on diet, however, which is very beneficial for health (such as via calorie restriction) but most likely of limited utility when it comes to extending human life. You can't eat your way to reaching 100 years of age with any certainty, and most people with superbly healthy lifestyles nonetheless age to death by 90. The future of longevity is modern medicine.

John Sperling

Sperling has funded a number of ventures of relevance to medicine and health, with a slant on longevity that is similar to the old school "anti-aging" businesses, such as Kronos Optimal Health. These are of no great utility when it comes to extending life: they are simply high end optional health services. At one point Sperling looked set to do much more and talked a good game about longevity, but per Wikipedia he is now more focused on environmental causes than human aging.

Dmitry Itskov

Itskov is taking the hard right turn in life in order to set up and promote his 2045 Initiative: tackle aging by moving out of biology and into machine bodies as soon as possible. He has a vision and is prepared to step up to the plate and put his reputation on the line in order to promote it with the financial muscle available to him. It's only a couple of years into this process, so we shall see how it goes once the initial run has settled down into the slow grind of advocacy, networking, and research funding. But from what we've seen so far, this is the sort of passion for a cause I'd like to see settle onto SENS rather than what looks like a much harder path to eliminate aging.

I'll say this for Itskov: a world in which a billionaire is prepared to openly and loudly back work on machine bodies and artificial minds is a world in which people don't laugh at high net worth individuals who back research into rejuvenation biotechnology. Once someone has planted a flag all the way out there on the field, other people become much more comfortable with what are now less radical gestures. We're somewhere in the middle of a sea change for the public perception of transhumanist technologies: robotics, AI, rejuvenation, and so forth. The cultural space within which people treated these fields as jokes and science fiction is vanishing rapidly, squeezed out by current events.

Source:
http://www.fightaging.org/archives/2013/05/bracketed-by-billionaires.php

Researchers recently published a set of encouraging data resulting from the use of stem cell transplants in the treatment of forms of leukemia. Once a particular new technique is adopted in medical practice, further progress is often a matter of steady incremental improvement. Here that improvement is quite considerable over the past decade, a reflection of the pace of medical science in general:

Survival rates have increased significantly among patients who received blood stem cell transplants from both related and unrelated donors. [The] study authors attribute the increase to several factors, including advances in HLA tissue typing, better supportive care and earlier referral for transplantation. The study analyzed outcomes for more than 38,000 transplant patients with life-threatening blood cancers and other diseases over a 12-year period - capturing approximately 70 to 90 percent of all related and unrelated blood stem cell transplants performed in the U.S.

At 100 days post-transplant, the study shows survival significantly improved for patients with myeloid leukemias (AML) receiving related transplants (85 percent to 94 percent) and unrelated transplants (63 percent to 86 percent). At one-year post-transplant, patients who received an unrelated transplant showed an increased survival rate from 48 to 63 percent, while the survival rate for related transplant recipients did not improve. Similar results were seen for patients with acute lymphoblastic leukemia (ALL) and myelodysplastic syndrome (MDS). In addition to improved survival, the authors note a significant increase in the overall number of patients receiving transplants. Related and unrelated transplant as treatment for ALL, AML, MDS and Hodgkin and non-Hodgkin lymphomas increased by 45 percent - from 2,520 to 3,668 patients annually. This is likely due to the use of reduced-intensity conditioning therapy and a greater availability of unrelated volunteer donors.

Link: http://www.sciencedaily.com/releases/2013/05/130528180857.htm

Source:
http://www.fightaging.org/archives/2013/05/stem-cell-transplants-for-leukemia-showing-improved-outcomes.php