Progress in DNA sequencing is similar to that of computing power in general - which is to say that overall capacity is increasing and cost per unit processed is falling at a staggering pace. Five years from now, sequencing your entire genome will likely cost less than the chair you're sitting on while reading this. Thus DNA sequencing is a poster child for speed of development in modern biotechnology: advances in understanding that would have required an entire research group and years of work a decade ago are now projects suitable for a single post-graduate researcher to complete over a semester off in one corner of the lab.

But so what? Why is this relevant to those of us following the early stages of the development of rejuvenation biotechnology? DNA sequencing seems like it's off to the side and down in the depths, one tiny part of the technologies involved in, say, repair of mitochondria or removal of senescent cells. Fortunately, here is one of the Halcyon Molecular folk to explain how DNA sequencing dovetails with the research we are interested in:

We are improving DNA sequencing to achieve our goal of turning biology into an information science. Along the way, various SENS approaches will be accelerated by improved DNA sequencing, and we present here specific experimental paths for using the tool in service of SENS. As one example, sequencing offers extreme technical shortcuts in molecular directed evolution techniques, allowing larger populations to be interrogated with fewer rounds of evolution and increased stringency of selection. This will accelerate attempts to find, improve, or evolve enzymes and other catalysts targeting age-related molecular damage. As another example, sequencing will enable better quality control of stem cells in both clinical and laboratory settings. We will discuss these specific experimental strategies and others that leverage improved sequencing to hasten progress toward saving lives via SENS therapy approaches.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

There have been a number of research results in the past year or two that suggest the barriers posed by age to the production of patient-specific cells suitable for stem cell therapies are lower than first thought. Several research groups have obtained useful cells from old patients, showing that age-related damage to patient cells is no barrier to reprogramming them - indeed, the reprogramming appears to repair many types of damage. Here is another such result: "Somatic cells reprogrammed into induced pluripotent stem cells (iPSCs) acquire features of human embryonic stem cells (hESCs) and thus represent a promising source for cellular therapy of debilitating diseases, such as age-related disorders. ... Aged somatic cells might possess high susceptibility to nuclear and mitochondrial genome instability. Hence, concerns over the [potential of reprogrammed cells to spawn cancer] due to the lack of genomic integrity may hinder the applicability of iPSC-based therapies for age-associated conditions. ... Four iPSC lines were generated from dermal fibroblasts derived from an 84-year-old woman, representing the oldest human donor so far reprogrammed to pluripotency. ... all aged-iPSCs were able to differentiate into neurons, re-establish telomerase activity, and reconfigure mitochondrial ultra-structure and functionality to a hESC-like state. Importantly, aged-iPSCs exhibited high sensitivity to drug-induced apoptosis and low levels of oxidative stress and DNA damage, in a similar fashion as iPSCs derived from young donors and hESCs. Thus, the occurrence of chromosomal abnormalities within aged reprogrammed cells might not be sufficient to over-ride the cellular surveillance machinery and induce malignant transformation through the alteration of mitochondrial-associated cell death. Taken together, we unveiled that cellular reprogramming is capable of reversing aging-related features in somatic cells from a very old subject, despite the presence of genomic alterations."

Link: http://dx.doi.org/10.1371/journal.pone.0027352

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

We are our brains, and so there isn't much room for outright replacement with new tissue as a strategy for regeneration anywhere inside the skull. Thus it is very important that researchers develop ways to repair the brain in situ. Fortunately, it looks as though this goal will be achievable sooner rather than later, with comparatively early stage stem cell therapies: "Neuron transplants have repaired brain circuitry and substantially normalized function in mice with a brain disorder, an advance indicating that key areas of the mammalian brain are more reparable than was widely believed. ... [Researchers] transplanted normally functioning embryonic neurons at a carefully selected stage of their development into the hypothalamus of mice unable to respond to leptin, a hormone that regulates metabolism and controls body weight. These mutant mice usually become morbidly obese, but the neuron transplants repaired defective brain circuits, enabling them to respond to leptin and thus experience substantially less weight gain. Repair at the cellular-level of the hypothalamus - a critical and complex region of the brain that regulates phenomena such as hunger, metabolism, body temperature, and basic behaviors such as sex and aggression - indicates the possibility of new therapeutic approaches to even higher level conditions such as spinal cord injury, autism, epilepsy, ALS (Lou Gehrig's disease), Parkinson's disease, and Huntington's disease. ... There are only two areas of the brain that are known to normally undergo ongoing large-scale neuronal replacement during adulthood on a cellular level - so-called 'neurogenesis,' or the birth of new neurons - the olfactory bulb and the subregion of the hippocampus called the dentate gyrus, with emerging evidence of lower level ongoing neurogenesis in the hypothalamus. The neurons that are added during adulthood in both regions are generally smallish and are thought to act a bit like volume controls over specific signaling. Here we've rewired a high-level system of brain circuitry that does not naturally experience neurogenesis, and this restored substantially normal function."

Link: http://www.eurekalert.org/pub_releases/2011-11/hms-rtb112311.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

You may recall that an Italian group has been engineering and transplanting comparatively simple organ structures - such as tracheas - in recent years. The researchers have used a range of techniques to build these organs from the patient's own cells, such as decellularization and nanoscale polymer scaffolds. The former requires a donor organ to be stripped of cells in order to provide a scaffold formed of its extracellular matrix, while the latter results in a completely synthetic organ. In both cases, the raw materials that form that scaffold are populated with the patient's own cells, leading to a transplant without the risk of immune rejection.

This is all very promising groundwork for later and more extensive tissue engineering of replacement parts to order. The first synthetic trachea transplant occurred earlier this year, and an update is doing the rounds:

The Eritrean patient, 36-year-old Andemariam Teklesenbet Beyene, was the first person in the world to receive this type of transplant in June, 2011 at the Karolinska University Hospital, Stockholm, Sweden. ... Currently Beyene is living in Reykjavík, Iceland, where he is a geology student studying for his PhD. Beyene's wife and two children live in Eritrea. ... The patient has been doing great for the last 4 months and has been able to live a normal life. After arriving in Iceland at the start of July, he was 1 month in hospital and another month in the rehabilitation center. Already at the rehabilitation center he could start to work on his Master of Science Thesis in Geophysics, a scientific project that he has been working on for the last years at the University of Iceland here in Reyklavik. For the last two months he has been able to focus on his studies and the plan is the he will defend his thesis at the end of this year.

...

A 30-year-old man from Maryland, USA, who also had primary cancer of the airway, is the second patient to receive a bioartificial scaffold transplantation from Prof. Macchiarini. The scaffold used in this case was created from nanofibres and therefore, according to Prof. Macchiarini, represents a further advance from the transplant Beyene received. Prof. Macchiarini's team is now hoping to use the same technique in order to treat a 13-month old South Korean infant.

...

We will continue to improve the regenerative medicine approaches for transplanting the windpipe and extend it to the lungs, heart, and oesophagus. And investigate whether cell therapy could be applied to irreversible diseases of the major airways and lungs.

So good news all round so far - this is one of the more successful lines of work in tissue engineering, and with success so clearly demonstrated you can be certain that other clinics worldwide will adopt these techniques over the next few years.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers are foraging for longevity-related genes that have nothing to do with the known processes of life extension through calorie restriction: "We believe that for the first time, we have a biochemical route to youth and aging that has nothing to do with diet. ... The chemical variation, known as acetylation because it adds an acetyl group to an existing molecule, is a kind of 'decoration' that goes on and off a protein - in this case, the protein Sip2 - much like an ornament can be put on and taken off a Christmas tree ... Acetylation can profoundly change protein function in order to help an organism or system adapt quickly to its environment. Until now, acetylation had not been directly implicated in the aging pathway, so this is an all-new role and potential target for prevention or treatment strategies, the researchers say. The team showed that acetylation of the protein Sip2 affected longevity defined in terms of how many times a yeast cell can divide, or 'replicative life span.' The normal replicative lifespan in natural yeast is 25. In the yeast genetically modified by researchers to restore the chemical modification, life span extended to 38, an increase of about 50 percent. The researchers were able to manipulate the yeast life span by mutating certain chemical residues to mimic the acetylated and deacetylated forms of the protein Sip2. They worked with live yeast in a dish, measuring and comparing the life spans of natural and genetically altered types. ... When we give back this protein acetylation, we rescued the life span shortening in old cells. Our next task is to prove that this phenomenon also happens in mammalian cells."

Link: http://www.hopkinsmedicine.org/news/media/releases/hopkins_scientists_turn_on_fountain_of_youth_in_yeast

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A PDF document that I think you'll find interesting: "Reports on the latest research of what makes us unhealthy, or what could make us live longer, are common from magazines, newspapers and websites. Often, the messages get shortened so that it sounds like one risk factor dominates. The reality is that the way in which many relevant risk factors work together is still not yet fully understood, and there is an element of chance affecting the longevity prospects of each of us. ... the overarching context is consistent improvement in longevity worldwide. Life expectancy has only ever declined in a few countries subject to specific and significant negative mortality risk. While we need to examine the trees of individual risk factors, there is much to be said for pausing to look at the woods of the consistent achievement in longevity progress. Longevity Bulletin aims to provide a regular guide to the prospects for long lives. It presents and explains actuarial perspectives on population longevity and looks outside the profession for statistics, research and the latest thinking on related subjects. It is not intended as a comprehensive guide to everything new in longevity research but rather as a helpful companion for those interested in a most intriguing subject."

Link: http://www.actuaries.org.uk/research-and-resources/pages/longevity-bulletin

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Connections make the world go round - networking and relationships, if you like: establishing and maintaining them. This is just as true of companies and their employees and customers as it is of any collection of people. A company that manages relationships well is a company that will prosper. This is actually surprisingly hard, however, even with resolve and the best of intentions from all parties, as anyone who has been on the inside of that part of business life will attest to.

On this topic, I see that cryonics provider Alcor, under the guidance of CEO Max More, is making an effort to make its operations far more transparent and in the process improve relationships with both its members and the broader community of people interested in cryonics - a source of future supporters and growth for the business. So, for example, you see regular sets of posts reporting on operations, intentions, research, and other progress such as these at the Alcor blog:

CEO Report

The never-ending quest for cost reductions continues. A review of Alcor's utility bills and an examination of the roof space made it clear that thousands of dollars per year have been avoidably incurred in the form of unnecessarily high air conditioning bills. We have asked for bids from three companies and will choose one in the coming week to improve insulation and install radiant barriers. Judging by the remarkable escalation in billing during the hotter months (in some units of the building more than others), the annual savings should make this investment pay off in a pleasingly short time.

...

On the communications front, Barry Aarons is helping us deploy the Alcor Speakers' Bureau to give talks to organizations in the area. A few weeks ago, we started this effort modestly with me giving a talk to the Midtown Lion's Club. The goal is to build a reputation and have a voice in the influential local business groups.

Readiness and Transport Report

An Alcor member in the New York area was placed on a ventilator following a recent serious medical event. Catherine Baldwin of Suspended Animation (SA) traveled to the area to establish a relationship with the medical facility and mortuary in the event stabilization was needed. Although the member's health has temporarily improved it was decided that a full standby was not warranted, she continues to struggle with her illness and may eventually need our services.

Research and Development

Based on our findings last month that the mylar cooldown blanket significantly reduced the LN2 usage of our automated perfusion and cooldown table with an empty patient pod, Steve Graber decided to conduct a more rigorous cooldown test utilizing four 20L water bladders in the pod cavity and a target cooling temperature of -80C.

If you look at the recent administrative report, you'll find a link to the membership and cryopreservation counts in graphical form for the last forty years - which is food for thought:

As of October 31, 2011, Alcor has 951 members and 108 patients.

In the grand scheme of things, cryonics has yet to climb into the big leagues. The potential is there, and much like the potential for rejuvenation biotechnology, there are great challenges inherent in trying to convince people to see it and believe it. "Why isn't cryonics a multi-billion dollar international industry?" is one of those questions like "Why don't more people wholeheartedly support research into reversing human aging?" - we can talk around the issue a great deal, but there are few firm answers at the end of the day. If we knew definitively where the point of failure was in persuasion and desire, why exactly the urge to spend money on the expectation of more life, so very much in evidence elsewhere, peters out for cryonics and longevity science, then we'd be working on fixing that problem as opposed to working on the various problems and challenges we only believe to be significant.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

A reminder that progress in the production of nanoscale scaffolds and surfaces is just as important as progress in biology in the stem cell field: "It's easy to give a stem cell a goal in life, apparently. Simply placing a cell in contact with a surface can provide sufficient information (a cue) to dictate how the cell will develop, and incredibly, even simple length-scale changes are enough to affect the outcome of the cell development. Far-fetched as this may sound, if you think about the nature of stem cells for a moment, it becomes less surprising that they are so responsive to their environment: how else to explain the extraordinary variety of cell types that derive from a uniform base material? As stem cells continue to be the focus of much research into the concepts of regenerative medicine and tissue engineering, a corollary challenge for materials science is the design and build for artificial substrates that can mimic biological environments and thereby control the growth and specialization of the cells. For one thing, the subtleties make it easy to grow off in the wrong direction. Growing muscle tissue will need a different set of conditions from, say, a new liver, but the differences in the environment might turn out to be very slight. A small change in the period of a pattern on the substrate might result in completely the wrong kind of tissue. A challenge of a more mechanical nature is the actual fabrication of the substrates. Most cell-growth environments have cues that act over a number of different length scales, with multiple patterns and features of various sizes interacting to produce the end result. Current micro- and nanofabrication techniques don't mimic this complexity too well, or rather, don't mimic it too well without complex multi-step procedures, expensive instrumentation, and expertise on fabrication that is not readily available to medical researchers."

Link: http://www.materialsviews.com/details/news/1400141/Shrink-Wrap_Stem_Cell_Growth.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

The Genomics X Prize has been a while in the building, and has a focus on the genetics of human longevity. It has been in the news of late: "The contest to sequence 100 complete human genomes of people who are over 100 years old in one month for $1,000 or less per genome has started its recruitment process and has pulled in new several new partners to help it develop its sampling, protocols, informatics, and other scientific needs. ... The Archon Genomics X PRIZE [is] an incentivized prize competition that will award $10 million to the first team to rapidly, accurately and economically sequence 100 whole human genomes to a level of accuracy never before achieved. The 100 human genomes to be sequenced in this competition will be donated by 100 centenarians (ages 100 or older) from all over the world, known as the Medco 100 Over 100. Sequencing the genomes of the Medco 100 Over 100 presents an unprecedented opportunity to identify those 'rare genes' that protect against diseases, while giving researchers valuable clues to health and longevity. These centenarians' genes are providing us with a window to the past that will significantly impact the future of healthcare. The result will be the world's first 'medical grade' genome, a critically-needed clinical standard that will transform genomic research into usable medical information to improve patient diagnosis and treatment. This global competition will inspire breakthrough genome sequencing innovations and technologies that will usher in a new era of personalized medicine."

Link: http://genomics.xprize.org/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Long after the time in which anyone can easily recall who was US president in 2011, or what party was in power, or which wars of declining empire are fought, and then long after anyone even cares about that ancient history, and later, long after the whole download slope of the history of the US is but a footnote of interest to scholars of the transition from second to third millennium, and later still, long after anyone can even find out with any great reliability who was US president in 2011, the first half of the 20th century will be recalled as the dawn of the era in which aging was conquered.

Progress in science and technology is really the only thing that matters in the long term. In that area of human endeavor, the truly transformative advances stand out like beacons across millennia of time - even long after the details of that period are hard to reconstruct, archaeologists can show clearly both when and how the use and understanding of technology changed. So we see the impact of agriculture and we know when it began, for example: it looms large in our considerations of deep human history at the present time, because it utterly transformed the course of our species. Similarly for iron working, and other important advances.

The advent of ways to reverse the effects of aging, largely through biotechnologies in the early stages of development that will repair the low-level biochemical damage that causes aging, will transform the shape and course of human society no less than the great advances of prehistory and early history - but undoubtedly much faster, as we're far better at talking to one another and coordinating our efforts in these years.

So in the final analysis, how much of what we do in our day to day lives actually matters? That's a meaning of life sort of a question, so everyone gets to write their own answer into the box and it's still right, but it's intended to provoke thought. Do you care about end results, or do you care about the journey? Billions of lives in the future hang in the balance of a few dollars or a convincing argument for the development of rejuvenation biotechnology: it's early enough still that we're talking butterfly wings and hurricanes when it comes to how our efforts today will affect the next four decades of progress in ways to slow and reverse aging. I suppose, for someone like myself who isn't in it so much for the journey, it's the case that you can choose to live a life in which you made a difference, or you can choose to live a life in which it doesn't much matter whether you ever existed.

The future can be made a golden place within our lifetimes, and billions of people who are presently destinated to suffer and age to death could instead by saved through biotechnology to live full, healthy, and vigorous lives thousands of years long. That all depends on how well and rapidly the present research community works on the first generation of rejuvenation therapies, which in turn depends on acts of fundraising and persuasion carried out by otherwise ordinary folk like you and I. There's an avalanche to be started here, a few pebbles that will bring the whole slope rushing down with it, profoundly transform humanity in the process by banishing aging and the decrepitude, disease, and death it brings.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm