Fight Aging!

FIGHT AGING! NEWSLETTER
April 11th 2011

The Fight Aging! Newsletter is a weekly email containing news, opinions, and happenings for people interested in aging science and engineered longevity: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives. This newsletter is published under the Creative Commons Attribution 3.0 license. In short, this means that you are encouraged to republish and rewrite it in any way you see fit, the only requirements being that you provide attribution and a link to Fight Aging!

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CONTENT

- An Update on Laser Ablation of Lipofuscin
- A Few Large Numbers
- Growing a Retina in a Dish
- The Balance Between Cancer and Aging
- Discussion
- Latest Headlines from Fight Aging!

AN UPDATE ON LASER ABLATION OF LIPOFUSCIN

The Immortality Institute raised funds in 2009 to run tests of laser ablation of lipofuscin, and this work is picking up again after a hiatus.

https://www.fightaging.org/archives/2011/04/hell-let-folk-know-when-the-worm-zapping-commences.php

"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."

In the discussion thread for the project, linked in the post above, you'll find photography of the lab where the remaining tests are to take place, and updates from the researcher.

A FEW LARGE NUMBERS

A short list of large sums of money, offered without comment. You'll find supporting links in this post:

https://www.fightaging.org/archives/2011/04/a-few-large-numbers.php

- Between 1970 and 2000, increasing life expectancy added $3.2 trillion per year in effective wealth.
- The yearly cost of natural death: more than 50 million lives and $100 trillion in wealth.
- The estimated cost of developing robust rejuvenation in mice via SENS, the Strategies for Engineered Negligible Senescence: $100 million per year over ten years.
- The 2010 budget for the US National Institute on Aging: $1 billion.
- The 2010 budget for the US National Institutes of Health: in the vicinity of $35 billion.
- The NIH comprises perhaps a third of medical research funding in the US.
- The cost of acquiring sirtuin research company Sirtris: $720 million.
- The 2010 research budget at the SENS Foundation: a little over $650,000.

GROWING A RETINA IN A DISH

Researchers continue to improve their ability to control stem cells:

https://www.fightaging.org/archives/2011/04/growing-a-retina-in-a-dish-from-embryonic-stem-cells.php

"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. ... 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 BALANCE BETWEEN CANCER AND AGING

Complex animals - such as we humans - have evolved to a point of balance in the operation of mechanisms controlling cell proliferation that both suppress cancer and accelerate aging:

https://www.fightaging.org/archives/2011/04/p16-and-the-balance-between-cancer-and-aging.php

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

"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."

DISCUSSION

The highlights and headlines from the past week follow below. Remember - if you like this newsletter, the chances are that your friends will find it useful too. Forward it on, or post a copy to your favorite online communities. Encourage the people you know to pitch in and make a difference to the future of health and longevity!

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LATEST HEADLINES FROM FIGHT AGING!

MITOCHONDRIA AS A THERAPEUTIC TARGET FOR AGING AND NEURODEGENERATION
Friday, April 8, 2011
https://www.fightaging.org/archives/2011/04/mitochondria-as-a-therapeutic-target-for-aging-and-neurodegeneration.php
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."

MITOCHONDRIAL MECHANISMS AND AGING
Friday, April 8, 2011
https://www.fightaging.org/archives/2011/04/mitochondrial-mechanisms-and-aging.php
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.

PROGRESS IN METHUSELAH FOUNDATION'S SILVERSTONE INVESTMENT
Thursday, April 7, 2011
https://www.fightaging.org/archives/2011/04/progress-in-methuselah-foundations-silverstone-investment.php
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."

A MODEST STEP TOWARDS LIMB REGROWTH IN MAMMALS
Thursday, April 7, 2011
https://www.fightaging.org/archives/2011/04/a-modest-step-towards-limb-regrowth-in-mammals.php
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."

MUSCLE REGENERATION VIA STEM CELLS
Wednesday, April 6, 2011
https://www.fightaging.org/archives/2011/04/muscle-regeneration-via-stem-cells.php
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."

THE METHUSELAH GENERATION
Wednesday, April 6, 2011
https://www.fightaging.org/archives/2011/04/the-methuselah-generation.php
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."

CALLING STEM CELLS TO WORK
Tuesday, April 5, 2011
https://www.fightaging.org/archives/2011/04/calling-stem-cells-to-work.php
Understanding how to manipulate the signaling systems that command stem cells into action will enable many of the same beneficial results as stem cell transplants: "The chemical which summons stem cells from bone marrow to the site of a wound has been discovered by scientists. The study identified the distress signal - HMGB1. The authors believe it can be used to put 'a megaphone in the system' to improve the treatment of injuries such as burns and leg ulcers. ... Bone marrow was thought to play a role in repairing damaged skin, but the exact process was unknown. Scientists [gave] mice bone marrow cells that glow green - which can be tracked while moving round the body. They then wounded the mice and some were given skin grafts. In mice without grafts, very few stem cells travelled to the wound. Those with grafts had many stem cells travelling to the wound. ... grafted skin tissue has no blood vessels and therefore no oxygen. ... this environment leads to the release of HMGB1 [which] results in stem cells moving to the wound. ... Researchers [are] developing a drug to mimic HMGB1. They hope to begin animal testing by the end of the year and human clinical trials shortly afterwards."

A REVIEW OF TELOMERE STUDIES
Tuesday, April 5, 2011
https://www.fightaging.org/archives/2011/04/a-review-of-telomere-studies.php
Telomere length seems to correlate with general levels of wellbeing. This article reports on: "several studies showing that psychological stress leads to shorter telomeres - the protective caps on the ends of chromosomes that are a measure of cell age and, thus, health. The findings also suggest that exercise may prevent this damage. ... [Researchers] examined telomeres in leukocytes, or white blood cells, of the immune system, which defends the body against both infectious agents and cell damage. ... Our findings suggest that traumatic and chronic stressful life events are associated with shortening of telomeres in cells of the immune system, but that physical activity may moderate this impact ... the current research [followed] for two years 63 healthy postmenopausal women who were the primary caregivers for a family member with dementia. In an earlier analysis of 36 of these women, pessimism was associated with high levels of a pro-inflammatory protein often associated with aging and disease states, and with short telomeres. In a recent and separate analysis of the full group of women, an increase in perceived stress was related to an increase in the odds of having short telomeres only in the non-exercising women. Among those who exercised, perceived stress was unrelated to telomere length. In the current analysis of the larger group, it was revealed that an increase in perceived stress over the course of one year was associated with a decrease in telomere length during that time. ... A third study [analyzed] data from 251 healthy, non-smoking women ages 50-65 of varying activity levels. The findings showed that non-exercising women with histories of childhood abuse had shorter telomeres than those with no histories of abuse. But, in those women who exercised regularly, there was no link between childhood abuse and telomere length, after controlling for body mass index, income, education and age."

AN INTERVIEW WITH THE CYTORI THERAPEUTICS CEO
Monday, April 4, 2011
https://www.fightaging.org/archives/2011/04/an-interview-with-the-cytori-therapeutics-ceo.php
Some interesting quotes can be found in this short piece: "We are at the beginning of a new age in medicine called Regenerative Medicine. The foundation of this is the living cell, although the emerging field will encompass a broad array of technologies. Remember the early days of the Computer Age circa 1978 where there were these new potentially powerful tools, but not a lot of software or applications? Today, almost everything we use or touch is in some way an offspring of this technology. Regenerative Medicine will explode in a similar way with new tools and applications and treatments, many of which are rapidly being developed around the world and I expect will ultimately impact the lives of billions of people. I predict that the innovations around these cell therapies will have as much impact on medicine as the silicon chip has had on technology. ... Medical tourism is gaining momentum worldwide. As the world becomes more 'flat,' medicine becomes somewhat of a commodity. With ever-increasing access to information, patients are doing more research on their conditions, and instead of only having access to treatment at their local medical facility, their reach becomes global. So when new technology is developed and available in one country and not another, savvy patients with the means to access it are able to identify, research, and ultimately receive the care they might not have otherwise. This hopefully will drive down the cost of care, speed the access to innovations, and raise the standard of care globally."

RECELLULARIZATION ATTEMPTED IN HUMAN HEARTS
Monday, April 4, 2011
https://www.fightaging.org/archives/2011/04/recellularization-attempted-in-human-hearts.php
The technique of recellularization has been used to prepare heart valves for transplant, and here researchers are attempting the whole heart: "US researchers have revealed they made the hearts by stripping cells from the hearts of people who had died, leaving behind the organ's tough protein skeleton, known as a 'ghost heart'. The researchers seeded eight ghost hearts with living human stem cells, which successfully stuck to them and then, crucially, started turning into heart cells. ... The hearts are growing and we hope they will show signs of beating within the next week. There are many hurdles to overcome to generate a fully functional heart, but the hope is that it may one day be possible to grow entire organs for transplant. ... It follows a series of successes by [researchers] in growing beating animal hearts. The team has also taken the ghost hearts of rats and pigs and seeded them with human stem cells. Again, the cells multiplied, colonised the structure and started to beat independently. The beating strength was up to 25 per cent that of a normal heart, but the fact the hearts were beating at all was seen as a triumph."

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