A Science News article here looks at the most well known and best funded research into slowing aging. It is all a matter of great expense to achieve very modest goals in slowing aging, and that almost as a side-effect of the main aim, which is to catalog and understand the biochemistry of metabolism.

A drug that postpones aging could also have profound health benefits, since most common diseases (such as cancer, heart disease and dementia) accompany old age. "That's what's driving us," says Donald Ingram, head of the nutritional neuroscience and aging laboratory at Pennington Biomedical Research Center in Baton Rouge, La. "We would like to see some kind of a product that would promote healthy aging."

So far, scientists have singled out a handful of synthetic and natural compounds that appear to trigger the same biochemical mechanisms that kick in when cells are partially starved of nutrients, part of a coping mechanism that protects against stress.

This sort of research accounts for the vast majority of funding in longevity science, and if that remains true then we'll live just a little bit longer than our parents. Perhaps as much as ten years longer if the metabolic engineers pull an unexpected amazing advance from their hats within the next decade.

From where I stand, that outcome would be a disaster - a missed opportunity with a cost of more than 50 million lives lost to aging and disease each and every year. If we reach 2040, after five decades of a scientific revolution in biotechnology, computing, and the ability to manipulate the fundamental components of life, and have not yet developed true rejuvenation biotechnology, capable of repairing the biochemical damage that causes aging ... well, we failed, and then some.

Presently, that grand failure through a focus on trivial success is exactly where the scientific and medical development community is headed. Their timelines are for drugs and metabolic manipulations that give a small number of additional years of life to emerge by 2030 - decades of tinkering, decades of trials, and we're all old by the time that any modestly useful result emerges into general use. Yet the research community, the public, and the press are all absolutely focused on slowing aging, where they think about aging at all. Far too few people realize just how damaging to our prospects this state of affairs will be in the long run.

This is why efforts like the SENS Foundation are so important: we need to see more groups building a platform, a body of work, and successfully making inroads into persuading the scientific community to work on repair of aging rather than just slowing it down. It won't take any longer to achieve meaningful success in repair-based research, given where things stand today, but the resulting difference to our lives and our health couldn't be greater.

From Depressed Metabolism: "It has been said that if you want to persuade someone, you need to find common ground. But one of the defining characteristics of cryonics is that proponents and opponents cannot even seem to agree on the criteria that should be employed in discussing cryonics. The cryonics skeptic will argue that the idea of cryonics is dead on arrival because cryonics patients are dead. The response of the cryonics advocate is that death is not a state but a process and there is good reason to believe that a person who is considered dead today may not be considered dead by a future physician. In essence, the cryonics advocate is arguing that his skeptical opponent would agree with him if he would just embrace his conception of death ... Cryonicists have named their favorite conception of death 'information-theoretic death.' In a nutshell, a person is said to be dead in the information-theoretic sense of the word if no future technologies are capable of inferring the original state of the brain that encodes the person's memories and identity. There are a lot of good things to be said about substituting this more rigorous criterion of death for our current definitions of death. However, in this brief paper I will argue that our best response does not necessarily need to depend on skeptics embracing such alternative definitions of death and that we may be able to argue that opponents of cryonics should support legal protection for cryonics patients or risk contradicting conventional definitions of death."

Link: http://www.depressedmetabolism.com/2011/05/16/neural-cryobiology-and-the-legal-recognition-of-cryonics/

With the advent of commercial telomere length measurement services, there's been a lot of unscientific hype in the media of late about tests that will show how long you're going to live. Some more sensible commentary here from FuturePundit: "the test can not precisely predict your year of death. Too many factors (accidents, suicide, and murder aside) influence your date of death. Take cancer for example. There's a lot of randomness involved in determining when we'll get cancer. The accumulation of damage in cells can make them turn cancerous. But just when the right set of genetic mutations or other cancer-promoting damage will occur in some cell in one's body is as hard to predict as when someone will win a lottery. Many things have to line up just right all in the same cell to make it cancerous. Every day is basically another throw of the dice. Will a bunch of mutations all line up to send a cell of yours into dangerous mad replication and growth? Better longevity tests seem useful for retirement planning. Should you save enough money to support yourself to age 95? Or expect to die by your late 60s? A telomere test could help you decide difficult questions about your savings rate and career choices. Do you need to work past age 70 to save enough money to avoid going broke in your 80s and avoid poverty in your 90s? A better sense of the odds would help. Of course, before we hit our biological shelf life expiration date some of us just might live long enough to still be around when rejuvenation therapies become available. Injections of youthful stem cells with long telomeres could replace older tired cells with short telomeres. This would be great for the immune system, for example, because a youthful immune system will do a better job of fighting cancer. Also, youthful cells for the cardiovascular system could cut the risk of heart disease, stroke, and other killers." The high level point being that unless you are old already the future of your life span has less to do with your telomeres and more do to with progress in medical science.

Link: http://www.futurepundit.com/archives/008089.html

One of the most interesting things to emerge from a rigorous comparison of the biology of aging between species is the role of cell membrane composition, as outlined in the membrane pacemaker hypothesis.

The membrane pacemaker hypothesis predicts that long-living species will have more peroxidation-resistant membrane lipids than shorter living species.

Resistance to oxidative damage is of particular importance in mitochondria, cellular power plants that progressive damage themselves with the reactive oxygen species they produce as a byproduct of their operation - and that gives rise to a chain of further biochemical damage that spreads throughout the body, growing ever more harmful as you age. Less damage to the mitochondria should mean slower aging, and thus more resistant mitochondrial membranes should also mean slower aging.

The evidence for this view is good, and continues to accumulate. See, for example, investigations of the biology of naked mole rats and other long-lived species with unusual biochemistries. As this recent review paper notes:

The relationship between membrane fatty acid composition and longevity is discussed for (1) mammals of different body size, (2) birds of different body size, (3) mammals and birds that are exceptionally long-living for their size, (4) strains of mice that vary in longevity, (5) calorie-restriction extension of longevity in rodents, (6) differences in longevity between queen and worker honeybees, and (7) variation in longevity among humans. Most of these comparisons support an important role for membrane fatty acid composition in the determination of longevity. It is apparent that membrane composition is regulated for each species. ... The exceptional longevity of Homo sapiens combined with the limited knowledge of the fatty acid composition of human tissues support the potential importance of mitochondrial membranes in determination of longevity.

This, I think, is one of the best illustrations for the merits of comparative studies of the biology of aging. Absent data from a range of different species, it seems unlikely that the membrane pacemaker hypothesis would have gathered as much interest in the community. Here's a related commentary:

Comparative biology plays several roles in our understanding of the virtually ubiquitous phenomenon of aging in animals. First, it provides a critical evaluation of broad hypotheses concerning the evolutionary forces underlying the modulation of aging rate. Second, it suggests mechanistic hypotheses about processes of aging. Third, it illuminates particularly informative species because of their exceptionally slow or rapid aging rates to be interrogated about potentially novel mechanisms of aging. Although comparative biology has played a significant role in research on aging for more than a century, the new comparative biology of aging is poised to dwarf those earlier contributions

For my part, focused as I am on the biotechnologies of human longevity, I see the most important aspect of this discussion being that it draws more attention to mitochondria, mitochondrial structure, and the prospects for mitochondrial repair. Clearly it is the case that human mitochondria serve well for the first few decades of life, and it is only later that the level of mitochondrial damage becomes large enough for degenerative aging to become materially apparent.

From Alcor News: "The Alcor Video Library has recently added new material. It now includes a short Video Tour of Alcor Facility and five complete presentations from the 2006 Alcor Conference. The video quality has also been significantly upgraded. ... The Limitless Future (28-minutes). Alcor documentary video (2005). Discover how leading-edge science at the Alcor Life Extension Foundation is getting closer to making the dream of a vastly extended lifespan come true and how our notion of "death" is shifting. Includes interviews with world-renowned scientists including Dr. Aubrey de Grey, [explaining] how life can be cryopreserved on the verge of death and then revitalized, giving us a second chance at a long and productive life, and Dr. Ralph Merkle, Distinguished Professor of Computing at Georgia Tech, exploring how molecular-sized machines will be able to repair damage to your body from aging or the devastating effects of cancer and other illnesses, including frostbite." You might also take a look at some of the other videos linked in the post, such as a presentation on the economics of longevity: "In this talk, Dr. Friedman shares his insights into the many potential consequences of an extended lifespan. He asks provocative questions about the future of the family unit, a typical career path, and the economic outlook for society as a whole."

Link: http://www.alcor.org/blog/?p=2040

Patching a damaged heart is on the agenda again, with nanoscale-featured scaffold material this time: "When you suffer a heart attack, a part of your heart dies. Nerve cells in the heart's wall and a special class of cells that spontaneously expand and contract - keeping the heart beating in perfect synchronicity - are lost forever. [At present] surgeons can't repair the affected area [but the] best approach would be to figure out how to resuscitate [it] ... scientists turned to nanotechnology. In a lab, they built a scaffold-looking structure consisting of carbon nanofibers and a government-approved polymer. Tests showed the synthetic nanopatch regenerated natural heart tissue cells ­- called cardiomyocytes - as well as neurons. In short, the tests showed that a dead region of the heart can be brought back to life. ... the engineers employed carbon nanofibers, helical-shaped tubes with diameters between 60 and 200 nanometers. The carbon nanofibers work well because they are excellent conductors of electrons, performing the kind of electrical connections the heart relies upon for keeping a steady beat. ... In tests with the 200-nanometer-diameter carbon nanofibers seeded with cardiomyocytes, five times as many heart-tissue cells colonized the surface after four hours than with a control sample consisting of the polymer only. ... The scaffold works because it is elastic and durable, and can thus expand and contract much like heart tissue. ... It's because of these properties and the carbon nanofibers that cardiomyocytes and neurons congregate on the scaffold and spawn new cells, in effect regenerating the area."

Link: http://www.eurekalert.org/pub_releases/2011-05/bu-rcn051711.php

I was reminded today that the Foresight Institute is holding an event next month, on June 25th-26th in the Bay Area, California. Some of the speakers and topics are relevant to those of us interested in longevity science, such as William Andregg of Halcyon Molecular, a fellow who has no problems in speaking his mind when it comes to achieving radical extension of the healthy human life span. The conference reminder came with a $50 discount to the conference registration price for Fight Aging! readers - just enter FIGHTAGING when registering.

Join friends old and new this summer at Google's Mountain View headquarters in Silicon Valley as we explore the future of nanotech with a rockstar lineup of nanotech experts and entrepreneurs.

Want to understand the science behind the dream? Find out why Sir Fraser Stoddart's successful development of molecular switches and motor-molecules merited him a knighthood. Talk molecular robotics with Ari Requicha, or molecular computation with quantum theorist William A Goddard, III. See single atoms with microscopist Andrew Bleloch, hear how Feynman Prize-winner Christian Schafmeister builds macromolecules, and find out how rising star Matt Francis is shaking up the world of synthetic biology.

Want innovative entrepreneurial applications? Hear word from the nanostartup trenches with Halcyon Molecular founder William Andregg and "Mad Scientist" One-Nano CEO Rob Meagley. Find out about new nanotech initiatives from IBM's decade-long, worldwide Director of Physical Sciences, Thomas Theis. Learn the practical impact of nanotech innovation in a forecast from futurist expert Paul Saffo, or the problems of financing them with Founders Fund partner and Paypal founder Luke Nosek.

For some pointers as to why progress in the field of nanotechnology is important for longevity science, you might look back in the Fight Aging! archives. Bear in mind that, as a bottom line, everything that goes wrong as we age is caused by atoms and molecules that are out of place. Progress in biotechnology is very much a matter of learning how to - as precisely as possible - identify and manipulate certain problematic atoms and molecules:

• Dreams of Molecular Nanotechnology
• The Desires Made Real By a Mature Molecular Manufacturing Technology Base

Systems that can identify, manage and place trillions of molecules accurately are not a pipe dream; after all, we are already surrounded by examples. You, for example, are just such a system, albeit somewhat slow at self-assembly to full size. There's nothing in the laws of physics that jumps out and says we can't do this. It's just a matter of time.

If you have the technology base to build a nanoforge to assemble a brick, then you also have the technology base capable of simultaneously assembling and controlling a hundred million medical nanorobots of arbitrary design and programming. Or an artifical lung better than the real thing, or replacements for immune cells that never get old or worn. You get the idea. A brick is just as complex as any portion of the human body if you have to build the thing molecule by molecule; more fault-tolerant, but just as complex.

Stem cell therapies are one theoretical path towards therapies for sarcopenia, the loss of muscle mass and strength with age. Here, researchers have discovered "the mechanism that causes stem cells in the embryo to differentiate into specialised cells that form the skeletal muscles of animals' bodies. ... The field has the potential to revolutionise medicine by delivering therapies to regenerate tissue damaged by disease or injury. Differentiation happens soon after fertilisation, when embryonic cells are dividing rapidly and migrating as the animal's body takes shape. ... The scientists investigated the effect of a known signalling pathway called NOTCH on muscle differentiation. They found that differentiation of stem cells to muscle was initiated when NOTCH signalling proteins touched some of the cells. These proteins were carried by passing cells migrating from a different tissue - the neural crest - the progenitor tissue of sensory nerve cells. Muscle formation in the target stem cells occurred only when the NOTCH pathway was triggered briefly by the migrating neural crest cells. ... This kiss-and-run activation of a pathway is a completely novel mechanism of stem cell specification which explains why only some stem cells adopt a muscle cell fate. ... the team would now focus on unravelling the mechanisms of embryonic muscle cell differentiation at the molecular level as a necessary step to regulating regeneration of the muscles in human patients."

Link: http://www.monash.edu.au/news/show/stem-cell-study-could-pave-the-way-to-treatment-for-age-related-muscle-wasting

From the SENS Foundation: "SENS Foundation is a 501c3 non-profit which works to develop, promote and ensure widespread access to rejuvenation biotechnologies which comprehensively address the disabilities and diseases of aging. The Foundation combines significant direct research efforts with education, affiliation and outreach programs. The SENS Foundation Academic Initiative (AI) is the nexus of its educational activities, which includes student mentoring, small but growing grants and scholarship programs, and coursework development. SENS Foundation is seeking a staff member to be Academic Coordinator. The Academic Coordinator will oversee the Academic Initiative and be responsible for designing, implementing and expanding projects and programs that support the aims of SENS Foundation. Additional responsibilities will include managing AI volunteer staff and students; maintaining active communication with SENS Foundation management, the Foundation Research Center, and AI volunteers; and establishing and maintaining reporting measures to document AI operations. The AC will report to the CEO, and work closely with the CSO, Vice President, and Director of Research Operations. Major projects already in development include the creation of online undergraduate courses in longevity science, development of a comprehensive training program, continuance and expansion of the scholarship and mentoring program, and implementation of a comprehensive marketing strategy to expand and promote the Academic Initiative."

Link: http://www.sens.org/node/2017

Many lower animals can regenerate from injuries that mammals cannot naturally heal - yet the fundamental components of their biology are much the same when considered at a high level. It's all cells and signalling molecules under the hood, and we're all sitting on branches of the same evolutionary tree. So it seems very plausible that there is something to be learned about regeneration from the biochemistries of species that can regrow lost limbs, completely heal heart injuries, or even grow half a body when needs must. Here is a small selection of research from the past week or so, illustrative of the work of a number of scientists investigating animals ranging from flatworms to salamanders.

Zebrafish Regrow Fins Using Multiple Cell Types, Not Identical Stem Cells

What does it take to regenerate a limb? Biologists have long thought that organ regeneration in animals like zebrafish and salamanders involved stem cells that can generate any tissue in the body. But new research suggests that multiple cell types are needed to regrow the complete organ, at least in zebrafish.

...

Limb regeneration has long captured people's imaginations.Traditionally, when people have looked at how a limb regenerates, they see a group of cells forming at the amputation site and the cells all look the same. So they've imagined that these cells have lost their identities and can become anything else. Our results show that this is not the case in the zebrafish fin. And there is mounting evidence that this is not the case in the salamander limb. ... This is evidence that we can't necessarily do regenerative medicine by plopping in generalized stem cells. The key may be to induce the cells that are already there to grow again. We need to understand and account for every cell lineage and then convince them to play ball together.

And just to show that there's no consistency whatsoever in nature, the story for the humble planarian appears to be quite the opposite.

Pluripotent adult stem cells power planarian regeneration

Ever since animals, such as lizards and starfish, were observed regenerating missing body parts, people have wondered where the new tissues come from. In the case of the planarian flatworm, Whitehead Institute researchers have determined that the source of this animal's extraordinary regenerative powers is a single, pluripotent cell type.

...

This is an animal that, through evolution, has already solved the regeneration problem. We're studying planarians to see how their regeneration process works. And, one day, we'll examine what are the key differences between what's possible in this animal and what's possible in a mouse or a person.

Heads or tails? Worm with abundant ability to regenerate relies on ancient gene to make decisions

This amazing ability of the planarian flatworm to regenerate its entire body from a small wedge of tissue has fascinated scientists since the late 1800s. The worms can regrow any missing cell or tissue - muscle, neurons, epidermis, eyes, even a new brain. Now Petersen and colleague Peter Reddien of the Massachusetts Institute of Technology (MIT) have discovered that an ancient and seldom-studied gene is critical for regeneration in these animals. The findings may have important ramifications for tissue regeneration and repair in humans.

...

In the paper, the authors describe how the gene notum acts at head-facing wounds as a dimmer switch to dampen the Wnt pathway and promote head regeneration. When the head or tail of a planarian is cut off, Wnt is activated. This Wnt activity turns on notum, but only at head-facing wounds. In a feedback loop, notum then turns Wnt down low enough that it can no longer prevent a head from forming. In tail-facing wounds, however, notum is not activated highly, a condition that promotes tail regrowth. (It takes the worm about a week to regrow a head or tail.)

The researchers are intrigued by this new role for notum. Like the Wnt signaling pathway, notum is highly conserved throughout species, from sea anenomes to fruit flies to humans, but little is known about its roles in biology. Because both notum and the Wnt signaling pathway are so evolutionarily ancient, their interaction in planarians may indicate a relationship that is important in other animals as well.

Wnt appears in a lot of published research into regeneration - it's clearly important in these processes, and the more that becomes known about the signalling systems of which it is a part, the better.