Biomedical gerontologist Aubrey de Grey is one of the figures appearing in the documentary film "How to Live Forever." It's played straight but isn't a serious piece, as this review notes:

It's a huge subject, vital to every living person in the world - what it means to grow old and how one can cheat or at least postpone mortality. Fortunately, Mark S. Wexler eschews ponderousness in favor of a wry, observant, open-minded approach in his most informative and often quite funny documentary How to Live Forever. ... The film opens May 13 in New York followed by a national expansion May 22.

Still, there you have Aubrey de Grey in theater distribution (again) - and the more folk to hear his message, the better. It's still the case that the vast majority of people are not aware of the state of the art in longevity science, the near term potential for progress towards the repair of aging, and how to help make it all happen. For all the work of advocates over the years, this message remains insufficiently repeated and too quiet.

Another commentary is entitled "A Little More Fear of Death, Please?":

The title is something of a misnomer: with his mother gone, and himself on the downslope of 50, Mark Wexler makes a general study of life-extension experts, self-proclaimed and otherwise. ... Wexler's "wisest" friend, Pico Iyer, tells him that death's finality makes sense of life (for who?), but the director barely addresses the fear of death [and] his grief over the loss of a parent is neither as intense nor as personal as, say, Ross McElwee's in Time Indefinite. ... Wexler settles on the lasting resonance of art as mortality's consolation prize. ... His film, though, is a cutesy binder of folk remedies offering inadequate balm.

A little more fear of death indeed - a sentiment I endorse. What's not to fear about the downward slope of degeneration, increasing frailty, pain, suffering, and the calm madness of a world that accepts all this and does next to nothing about it?

Biomedical gerontologist Aubrey de Grey is one of the figures appearing in the documentary film "How to Live Forever." It's played straight but isn't a serious piece, as this review notes:

It's a huge subject, vital to every living person in the world - what it means to grow old and how one can cheat or at least postpone mortality. Fortunately, Mark S. Wexler eschews ponderousness in favor of a wry, observant, open-minded approach in his most informative and often quite funny documentary How to Live Forever. ... The film opens May 13 in New York followed by a national expansion May 22.

Still, there you have Aubrey de Grey in theater distribution (again) - and the more folk to hear his message, the better. It's still the case that the vast majority of people are not aware of the state of the art in longevity science, the near term potential for progress towards the repair of aging, and how to help make it all happen. For all the work of advocates over the years, this message remains insufficiently repeated and too quiet.

Another commentary is entitled "A Little More Fear of Death, Please?":

The title is something of a misnomer: with his mother gone, and himself on the downslope of 50, Mark Wexler makes a general study of life-extension experts, self-proclaimed and otherwise. ... Wexler's "wisest" friend, Pico Iyer, tells him that death's finality makes sense of life (for who?), but the director barely addresses the fear of death [and] his grief over the loss of a parent is neither as intense nor as personal as, say, Ross McElwee's in Time Indefinite. ... Wexler settles on the lasting resonance of art as mortality's consolation prize. ... His film, though, is a cutesy binder of folk remedies offering inadequate balm.

A little more fear of death indeed - a sentiment I endorse. What's not to fear about the downward slope of degeneration, increasing frailty, pain, suffering, and the calm madness of a world that accepts all this and does next to nothing about it?

Another part of the biochemical mechanisms of calorie restriction is uncovered in nematode worms: "The study [was] conducted on Caenorhabditis elegans (nematodes or roundworms), which are a widely accepted model for human aging research. ... Not only have we been able to identify some of these molecules for the first time in the worm, but we have also been able to show they act as a signal of nutrient availability and ultimately influence the worm's lifespan. What makes this important is that the same molecules are present in both humans and C. elegans, so these molecules may play similar roles in both organisms. ... The molecules identified in the new study are N-acylethanolamines (NAEs), a group of signaling molecules derived from lipids that help indicate nutrient availability in the environment and maintain an animal's internal energy balance. [Researchers showed that] NAE abundance in the worm is reduced during periods of dietary restriction, and that NAE deficiency in the presence of abundant food is sufficient to extend the animal's lifespan. ... It is well known that if you put C. elegans on a restricted diet, you can extend its lifespan by 40 to 50 percent. However, we were amazed to see that if you add back just one of these NAE molecules, eicosapentaenoyl ethanolamide, it completely abrogates the lifespan extension. ... Importantly, this particular NAE is similar to endocannabinoids in mammals, which regulate many different physiological processes including nutrient intake and energy balance, as well as inflammation and neuronal function."

Link: http://www.eurekalert.org/pub_releases/2011-05/sri-srs050511.php

For a variety of reasons lung tissue engineering has lagged behind foundational work on other organs - but there are signs that it is catching up: researchers "have identified a human lung stem cell that is self-renewing and capable of forming and integrating multiple biological structures of the lung including bronchioles, alveoli and pulmonary vessels. ... This research describes, for the first time, a true human lung stem cell. The discovery of this stem cell has the potential to offer those who suffer from chronic lung diseases a totally novel treatment option by regenerating or repairing damaged areas of the lung ... Using lung tissue from surgical samples, researchers identified and isolated the human lung stem cell and tested the functionality of the stem cell both in vitro and in vivo. Once the stem cell was isolated, researchers demonstrated in vitro that the cell was capable of dividing both into new stem cells and also into cells that would grow into various types of lung tissue. Next, researchers injected the stem cell into mice with damaged lungs. The injected stem cells differentiated into new bronchioles, alveoli and pulmonary vessel cells which not only formed new lung tissue, but also integrated structurally to the existing lung tissue in the mice."

Link: http://www.eurekalert.org/pub_releases/2011-05/bawh-hls051011.php

Following up on recently published research into changes in body temperature brought about by the practice of calorie restriction in humans, I see that a release from a few days ago contains some interesting remarks from the researcher:

Individuals who significantly reduce their calorie intake have lower core body temperatures compared to those who eat more. The new finding matches research in animals. Mice and rats consuming fewer calories also have lower core body temperatures, and those animals live significantly longer than littermates eating a standard diet. ... What is interesting about that is endurance athletes, who are the same age and are equally lean, don't have similar reductions in body temperature.

...

What we don't know is whether there is a cause/effect relationship or whether this is just an association. But in animal studies, it's been consistently true that those with lower core body temperatures live longer. ... in an unrelated study called the Baltimore Longitudinal Study of Aging, scientists found that men who had lower core body temperatures, probably for genetic reasons, lived significantly longer than men with higher body temperatures. So it appears body temperature may predict longevity in humans, too.

...

For now, animal models suggest that simply lowering body temperature isn't enough to increase lifespan. In mice and rats that regularly swam in cold water, core body temperature dropped due to exposure to the cold water. But those animals didn't live any longer than normal rodents. Fontana says it appears that how lower temperatures are achieved is important. "I don't think it ever will be possible to be overweight and smoking and drinking and then take a pill, or several pills, to lower body temperature and lengthen lifespan," he says. "What may be possible, however, is to do mild calorie restriction, to eat a very good diet, get mild exercise and then take a drug of some kind that could provide benefits similar to those seen in severe calorie restriction."

Calorie restriction is chiefly interesting for its beneficial effects on health and longevity - which are nothing short of stunning in comparison to any presently available medical technology. It's the best present option for immediately and rapidly improving the health of basically healthy people. The evidence for it and the effects in studied human populations are so good that - if you are essentially healthy, in good shape, and would like to stay that way for as long as possible - you'd really have to have be digging for excuses not to be practicing calorie restriction.

All that said, calorie restriction is only slowing aging - and if we want to do better, to avoid becoming frail and aging to death, the only viable path forward is biotechnology along the lines of the Strategies for Engineered Negligible Senescence. If repair technologies for our biology are not developed soon enough, then all we gain through calorie restriction is a healthy life, probably a little longer, almost certainly with a lower cost of medical treatment and fewer chronic diseases of aging. To do better than that, to regain the vigor and health of youth and obtain extra decades of life, we need to support and encourage rapid advances in medical technology.

More signs of progress in regenerative medicine: "researchers have demonstrated that human liver cells derived from adult cells coaxed into an embryonic state can engraft and begin regenerating liver tissue in mice with chronic liver damage. ... liver cells derived from so-called "induced-pluripotent stem cells (iPSCs)" could one day be used as an alternative to liver transplant in patients with serious liver diseases, bypassing long waiting lists for organs and concerns about immune system rejection of donated tissue. ... iPSC-derived liver cells not only can be generated in large amounts, but also can be tailored to each patient, preventing immune-rejection problems associated with liver transplants from unmatched donors or embryonic stem cells. ... Although the liver can regenerate in the body, end-stage liver failure caused by diseases like cirrhosis and cancers eventually destroy the liver's regenerative ability ... Currently, the only option for those patients is to receive a liver organ or liver cell transplant, a supply problem given the severe shortage of donor liver tissue for transplantation. In addition, mature liver cells and adult liver stem cells are difficult to isolate or grow in the laboratory."

Link: http://www.eurekalert.org/pub_releases/2011-05/jhmi-asc051011.php

Accumulating damage to mitochondrial DNA is one of the causes of aging, and here researchers investigate its role in the aging of stem cells: "Somatic stem cells mediate tissue maintenance for the lifetime of an organism. Despite the well-established longevity that is a prerequisite for such function, accumulating data argue for compromised stem cell function with age. Identifying the mechanisms underlying age-dependent stem cell dysfunction is therefore key to understanding the aging process. Here, using a model [that suffered a greater rate of mitochondrial DNA damage], we demonstrate hematopoietic defects reminiscent of premature [stem cell] aging, including anemia, lymphopenia, and myeloid lineage skewing. However, in contrast to physiological stem cell aging, rapidly accumulating mitochondrial DNA mutations had little functional effect on the hematopoietic stem cell pool, and instead caused distinct differentiation blocks and/or disappearance of downstream progenitors. These results show that intact mitochondrial function is required for appropriate multilineage stem cell differentiation, but argue against mitochondrial DNA mutations per se being a primary driver of somatic stem cell aging."

Link: http://www.ncbi.nlm.nih.gov/pubmed/21549326

I'll point out the results of a demographic and an associative study today: many of the leads followed up by life science researchers are first identified by showing there is some association between a particular trait or aspect of our biology and people who live longer, or have better health in old age. Firstly, I see that the Irish Longitudinal Study on Aging has published a weight of material, and a press release for those who like their summaries pre-digested:

TILDA is the most comprehensive study ever conducted on ageing in Ireland. Between 2009-2011, over 8,000 people aged 50 and over were randomly selected across the country and interviewed about many aspects of their lives including issues such as health, financial circumstances and quality of life. Almost 85 per cent of the participants also underwent a rigorous health assessment. The same group will be interviewed every two years until 2018.

...

A constant finding across the report is that those with higher levels of education and wealth are likely to enjoy better outcomes later in life.

Which reinforces data obtained from other large studies: the strong associations between wealth, intelligence, education, and health prospects in later life. These correlations have been discussed at Fight Aging! a number of times in past years. For example:

• Correlations in Biochemistry and Wealth
• Wealth and Longevity (for Individuals)
• Wealth and Longevity (for Populations)
• Revisiting the Link Between Intelligence and Longevity
• On Using the Tools to Hand

Moving on, you might recall hearing that grip strength is an excellent measure of frailty and thus risk of death in the old - and it correlates with all sorts of other measures of failing health and accumulating damage, such as the accumulation of AGEs. Here is another set of evidence in support of that biomarker:

We studied prospectively the midlife handgrip strength, living habits, and parents' longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu-Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965-1968, when they were 56-68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment.

...

Compared with people who died at the age of [less than] 79 years, centenarians belonged 2.5 times more often to the highest third of grip strength in midlife, were never smokers, had participated in physical activity outside work, and had a long-lived mother.

You can't do anything (yet) about the genes you were born with, but you can certainly work on the other line items listed above. You should expect good health to make a meaningful difference to your life expectancy - and bad health to make a meaningful difference in the opposite direction.

News of another potential way to manipulate mitochondrial function to slow aging: "Mitochondria are the body's energy producers, the power stations inside our cells. Researchers [have] now identified a group of mitochondrial proteins, the absence of which allows other protein groups to stabilise the genome. This could delay the onset of age-related diseases and increase lifespan. ... When a certain MTC protein is lacking in the cell, e.g. because of a mutation in the corresponding gene, the other MTC proteins appear to adopt a new function. They then gain increased significance for the stabilisation of the genome and for combating protein damage, which leads to increased lifespan. These studies also show that this MTC-dependent regulation of the rate of aging uses the same signalling pathways that are activated in calorie restriction - something that extends the lifespan of many different organisms, including yeasts, mice and primates. Some of the MTC proteins identified in this study can also be found in the human cell, raising the obvious question of whether they play a similar role in the regulation of our own aging processes. It is possible that modulating the activity of the MTC proteins could enable us to improve the capacity of the cell to delay the onset of age-related diseases. These include diseases related to instability of the genome, such as cancer, as well as those related to harmful proteins, such as Alzheimer's disease and Parkinson's disease. At the moment this is only speculation, and the precise mechanism underlying the role of the MTC proteins in the aging process is a fascinating question that remains to be answered."

Link: http://www.sciencedaily.com/releases/2011/05/110510074433.htm

From the Washington Post: "The machine looks like the offspring of an Erector Set and an inkjet printer. The 'ink' feels like applesauce and looks like icing. As nozzles expel the pearly material, layer by layer, you imagine the elaborate designs this device could make on gingerbread cookies. But the goo is made of living cells, and the machine is 'printing' a new body part. These machines - they're called three-dimensional printers - work very much like ordinary desktop printers. But instead of just putting down ink on paper, they stack up layers of living material to make 3-D shapes. The technology has been around for almost two decades, providing a shortcut for dentists, jewelers, machinists and even chocolatiers who want to make custom pieces without having to create molds. In the early 2000s, scientists and doctors saw the potential to use this technology to construct living tissue, maybe even human organs. They called it 3-D bioprinting, and it is a red-hot branch of the burgeoning field of tissue engineering. ... The possibilities for this kind of technology are limitless. Everyone has a mother or brother or uncle, aunt, grandmother who needs a meniscus or a kidney or whatever, and they want it tomorrow. ... The promise is exciting. The goal is not to squash that excitement, but to temper it with the reality of what the process is. ... The reality for now is that making such things as vertebral disks and knee cartilage, which largely just cushion bones, is far easier than constructing a complicated organ that filters waste, pumps blood or otherwise keeps a body alive. Scientists say the biggest technical challenge is not making the organ itself, but replicating its intricate internal network of blood vessels, which nourishes it and provides it with oxygen. Many tissue engineers believe the best bet for now may be printing only an organ's largest connector vessels and giving those vessels' cells time, space and the ideal environment in which to build the rest themselves; after that, the organ could be implanted."

Link: http://www.washingtonpost.com/national/science/2011/04/21/AFJM0WbG_print.html

Following on from the release of their 2010 research report, the SENS Foundation folk have issued their 2010 year-end report. Just as for the earlier research report, it is an interesting and closer look at the finances and research activities of the organization - one of the very few groups in the world whose leaders have the right idea when it comes to aging, longevity, and biotechnology.

In 2009 we launched SENS Foundation. We did it to drive biomedical research towards a functional and cost-effective approach to extending individual health. We did it to raise awareness for an alternative to an increasingly complex and problematic pathology chase in medicine; to redefine regenerative medicine as applied to aging; to enable doctors to think about fixing patients before they were sick.

We did it to transform the way you think about medicine. We knew it was a big agenda when we set out, and we were fully conscious of how small a public charity we were. We recognized that our first successful steps would depend upon our demonstration of fundamental credibility to the medical science community.

That is why I am especially pleased to present this 2010 end of year report. As you will read, we have created a mature organization and delivered the networks and collaborations needed to build the rejuvenation biotechnology field. We've expanded our own research programs and have used that expansion to develop collaborations with leading universities and research institutions in regenerative medicine, around the nation and the world. We have, in short, found our voice with a substantial and mainstream scientific community. Rejuvenation biotechnology, as a research field, is emerging, and SENS Foundation has led that charge.

If you like what you see, then help the Foundation achieve its mission. Donate, tell your friends, and write about what might be achieved soon through advanced biotechnology if there were just the will and the funding to do it. Bootstrapping a new industry and new view of medicine is a slow process, but every helping hand makes it faster.