Fight Aging!

LONGEVITY MEME NEWSLETTER
April 27 2009

The Longevity Meme Newsletter is a weekly e-mail containing news, opinions, and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology, and proven medical advances to live healthy, longer lives.

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CONTENTS

- Just Successful Enough to Do Ourselves Harm
- David Sinclair's Viewpoint
- An Interview With Aubrey de Grey
- The Medicines of 2030
- Discussion
- Latest Healthy Life Extension Headlines

JUST SUCCESSFUL ENOUGH TO DO OURSELVES HARM

The combination of the present stage in our technological development and our evolved urges has brought us to a temporary comfort trap:

https://www.fightaging.org/archives/001724.php

"As a species we are presently succeeding ourselves into a harmful pit. We've succeeded in the goals of our ancestors (eat, feel good, evade pain, become wealthy) to the point at which we're breaking the evolved metabolic processes intended to deal with a short and brutish life of privation. We became fat and now surround ourselves with more food than we need, in other words - not a condition that our bodies respond well to, and so we suffer for it. The collection of symptoms suffered as a consequence of being fat, not exercising enough, and eating a lot is termed 'metabolic syndrome.' It's a step along the way to more serious failures of your organs and bodily systems, such as diabetes, that result from the damage being done by fat through the years.

"Unfortunately, while we've succeeded enough to get into this hole, we've not yet succeeded enough to be able to dig our way out through medical science. Until that happens, indulgence will continue to have adverse consequences on your health and your longevity - lost years, lost money, sickness, and pain."

DAVID SINCLAIR'S VIEWPOINT

An article by David Sinclair of Sirtris, a company developing calorie restriction mimetics, was published last week. It's representative of the viewpoint of those researchers in the mainstream who believe the best path forward is to slow aging by manipulating our metabolic processes.

https://www.fightaging.org/archives/001723.php

"During the Victorian era, children commonly died of illnesses like measles, mumps, and whooping cough; surely, no one would suggest today that we eliminate prenatal care, vaccines, or water purification in order to return to a more 'natural' state. Now that we have the technology to eliminate the scourge of infant mortality, it would be immoral to not use it. In truth, we're fighting aging and extending lifespan every time a doctor prescribes a statin drug or recommends a healthier diet to a patient. And the fact remains that science has not yet discovered an indisputable biological 'expiration date' for a human life, nor is there good evidence that one exists.

"In time, the idea of an inevitable, debilitating decline starting at age 50 will seem as horrifying and primitive as it does for us, in the age of potent antibiotic cocktails, to imagine a young person in the 19th century dying from an infection caused by a splinter. As a society, we should not accept a terrible period of suffering, dependence, sickness, and frailty if we don't have to. There's nothing more natural than marshalling the body's own defenses to treat and heal itself, and that is precisely what longevity genes like SIRT1 do."

There is agreement on high level end goals in the more enlightened reaches of the research community, even if I don't think they're taking the best path forward. See the following link for more on the debate over research strategies for engineered longevity, and why manipulating metabolism is not all that great in the grand scheme of things:

https://www.fightaging.org/archives/001557.php

AN INTERVIEW WITH AUBREY DE GREY

The Immortality Institute folk interviewed biomedical gerontologist Aubrey de Grey for their Sunday Evening Update audio and video series, and you can stream the interview online. My comments are below:

https://www.fightaging.org/archives/001725.php

"I think we were all expecting greater things to result from the large donation made by entrepreneur turned venture capitalist Peter Thiel, in terms of further accelerating a sea change in opinion amongst philanthropists in any case. Of course, the research funded by that donation has produced progress, as Aubrey de Grey remarks in an open letter at the SENS Foundation site. As I noted a few months back, the matching portion of the Thiel donation expires at the end of this year - with much fundraising yet to go to hit the mark.

"Ultimately, you find out how fast things can go by trying them out. Looking at matters in a broader perspective, the Methuselah Foundation and its donors have raised more than $10 million since 2005. Back in the 1990s, comparable organizations with comparable messages were struggling to raise $100,000 over a similar time frame. The tide for engineered longevity is rising, lifting all boats with it, just not as fast as we'd like."

THE MEDICINES OF 2030

Speculation is a fool's game, but somehow we can't stay away:

https://www.fightaging.org/archives/001726.php

"Cards on the table: the wrong side of 40 looms for some of us. The present regulatory systems for medical development in the US and most other regions contributing meaningfully to progress don't look likely to become any less oppressive in the years ahead. It presently takes ten to twenty years to move a good research result out of trials and into the clinics, and that time frame is largely based on organizational activities and regulatory make-work that won't be speeded up by ongoing advances in biotechnology. Furthermore, the regulatory environment destroys or prevents many beneficial development programs by making them unprofitable.

"This means that present glimmers of medical technologies capable of repairing specific forms of biochemical damage, such as work on mitochondrial repair, will most likely not be available for general use until people like me are hitting 60. They won't ever be available for healthy people 'aging normally' inside US borders absent a revolution in the way the FDA operates. The same goes for organ replacement, other forms of growing any new tissue you like to order, rebooting the immune system, and so on.

"Here is today's speculation: will these technologies of 2030 be good enough to grant an additional 20 years of life? How much certainty will there be by that time that these technologies will extend life significantly in humans?"

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!

Reason

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LATEST HEALTHY LIFE EXTENSION HEADLINES

An Interesting View of Calorie Restriction (April 24 2009)
https://www.fightaging.org/archives/2009/04/an-interesting-view-of-calorie-restriction/
Here is an interesting open access paper at PLoS ONE: "We generated microarray gene expression data from livers of male mice fed high calorie or [calorie restriction] CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the sirtuin pathway. ... Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of females." So yet another theory to add to the many on the cause of longevity differences by gender.

Targeted Reprogramming of Cancer Cells (April 24 2009)
https://www.fightaging.org/archives/2009/04/targeted-reprogramming-of-cancer-cells/
A good example of the sort of cellular hacking going on in the laboratory and early trials these days via EurekAlert!: researchers "have developed a nanoparticle - about one thousandth smaller than a printed period - that can travel through the blood stream. 'Decorated' with a tumor-targeting antibody, the nanoparticle is able to locate primary and hidden metastatic tumor cells and deliver its payload: a fully functioning copy of the P53 tumor suppressor gene. ... Normal cells have two copies of the functioning P53 gene. The protein produced by the P53 gene is activated to either coordinate the repair process in cells or induce cell suicide. ... In earlier work using animal models, [researchers] delivered functional p53 genes to tumor cells and tumor metastases in 16 different types of cancer, including prostate, pancreatic, melanoma, breast cancer and head and neck cancer. The presence of the replacement genes dramatically improved the efficacy of conventional cancer therapy. ... When the job of reinstating a normal P53 suppressor gene is done, the nanoparticle - essentially a little fat droplet wrapped around the gene - simply melts away, unlike non-biodegradable delivery systems. ... Clinical trials are now underway ... The trial already has enrolled six patients with various cancers and anticipates a total of 14."

Theory: It's All Down To Autophagy (April 23 2009)
https://www.fightaging.org/archives/2009/04/theory:-its-all-down-to-autophagy/
As I've mentioned in the past, autophagy - the process by which cells destroy and replace damaged or old components - seems to be very important in the natural longevity you are granted by the operation of your metabolism. It's required for the longevity boost given by calorie restriction, for example. Some groups would go so far as to say that most or all longevity-inducing tweaks to metabolism operate through increased autophagy: "Autophagy is involved in cellular protein and organelle degradation, which is mediated by the lysosomal pathway. [Autophagy] has a key role in cellular housekeeping by removing damaged organelles. During aging, the efficiency of autophagic degradation declines and intracellular waste products accumulate. In Caenorhabditis elegans, there is clear evidence that lifespan is linked to the capacity to regulate autophagy. Recent studies have revealed that the same signaling factors regulate both aging and autophagocytosis, thus highlighting the role of autophagy in the regulation of aging and age-related degenerative diseases. Here, we examine in detail the interactions of the signaling network involving longevity factors SIRT1, mTOR, FoxO3, NF-kappaB and p53 in the regulation of autophagy. We discuss the possibility that these well-known stress resistance and longevity factors regulate the aging process via autophagy."

NPR On the Ongoing Biotech Revolution (April 23 2009)
https://www.fightaging.org/archives/2009/04/npr-on-the-ongoing-biotech-revolution/
Times are changing, and some very interesting and transformative technologies are emerging from the life sciences. Expect biotech to look increasingly like open source software development in years ahead: "at least three major technologies are shovel-ready: the programming of tissues, the ability to engineer cells, and robots. ... these discoveries mean that one can write out a life code, manipulate a cell, and execute a specific desired function. It means we can convert cells into programmable manufacturing entities. But this software builds its own hardware, allowing companies to begin using bacteria to produce chemicals, fuels, medicines, textiles, data storage, or any series of organic products. ... A second major tsunami is our increasing ability to grow complex organic structures, such as limbs, bladders, hearts, and tracheas. All complex organisms start out as undifferentiated, pluripotent cells, meaning these cells contain an entire genome and are able to produce all body parts. Mexico's dinosaur-like axolotl salamanders naturally regrow body parts, including sections of their hearts and brains as well as whole limbs. ... And soon, it may be possible to do this without a full body, just some cells. ... As innovators begin to read, reproduce, and program life, they will change almost every industry across the globe."

Recent Stanford Conference on Longevity Science (April 22 2009)
https://www.fightaging.org/archives/2009/04/recent-stanford-conference-on-longevity-science/
A report here on the recent conference at the Stanford Center for Longevity, representative of the dominant "work to slow aging through metabolic manipulation" faction in the research community: "Recent, near-miraculous advances in our understanding of biological processes at the cellular and molecular level offer the possibility of extending individual lives by slowing the aging process itself. ... Not that environment doesn't play a key role in aging-associated disease. For instance, the gene cited by Brunet is involved in the insulin pathway. Brunet, whose laboratory is studying aspects of this pathway in mammals as well as in C. elegans, noted that restricting caloric intake by about one-quarter to one-third - which suppresses insulin levels - has a life-span-increasing effect on all other species in which it's been tried: worms, flies, mice, even monkeys. Experiments with humans are ongoing, but our life spans are so long that data are dribbling out slowly. However, an apparent diminution in aging-related conditions such as type-2 diabetes, stroke and cancer is being seen, she said."

On Humanin (April 22 2009)
https://www.fightaging.org/archives/2009/04/on-humanin/
Via EurekAlert!, a look at humanin and longevity associated with the insulin signaling system: "Dr. Nir Barzilai reports that a small infusion of [Humanin] HN is the most potent regulator of insulin metabolism that his research team has ever seen, significantly improving overall insulin sensitivity and sharply decreasing the glucose levels of diabetic rats. ...Dr. Barzilai is internationally known as a leading discoverer of longevity genes ... Last year, he reported that some of the oldest in this group have mutations in the gene for insulin-like growth factor 1 (IGF-1) receptor, genetic alterations that have been shown to prolong life span in worms and some mammals. In this [presentation], he reports that, while the production of HN generally decreases as people age, it decreases less in the centenarians and is the highest in their offspring. Studies are now underway [to] determine if the centenarians have a mutation in the HN gene in the mitochondria." Insulin metabolism is one of the major areas of focus for researchers aiming to understand how rates of aging are determined by the operation of our metabolic processes.

Mannoheptulos as Calorie Restriction Mimetic (April 21 2009)
https://www.fightaging.org/archives/2009/04/mannoheptulos-as-calorie-restriction-mimetic/
The success of Sirtris at enriching its founders has given further impetus to the field of calorie restriction mimetic compounds. Scientists respond to the same incentives as the rest of us, after all. Here, Science News notes one of the latest lines of investigation. Researchers "have been mining avocados [for] MH (mannoheptulose)]. It's a fairly simple sugar with a 7-carbon backbone. When fed to mice in fairly concentrated doses (roughly 300 milligrams per kilogram of an animal's body weight), it improved insulin sensitivity and the clearance of glucose from the blood. Meaning it helped overcome diabetes-like impairments to blood-sugar control. MH supplementation also improved the ability of insulin, a hormone, to get cells throughout the body to do its bidding (and that's a good thing). MH revved up the burning of fats in muscle. That's the opposite of fat deposition and something that these scientists note 'would be an expected effect of a calorie restriction mimetic.' Treated mice also lived longer - some 30 percent longer than untreated animals. ... their food intake and weight matched that of untreated mice."

Learning From Cryonics History (April 21 2009)
https://www.fightaging.org/archives/2009/04/learning-from-cryonics-history/
An episode of NPR's This American Life looks at one unfortunate episode in early cryonics history: a failed provider who got in over his head, wherein the preserved bodies were lost. "It's the late 1960s, and in the new technology of cryonics, a California TV repairman named Bob sees an opportunity to help people cheat death. But freezing dead people so scientists can reanimate them in the future is a lot harder than it sounds. Harder still was admitting to the family members of people Bob had frozen that he'd screwed up. Badly." Caveat emptor should always be the motto - if you're interested in cryonics, be interested enough to learn about the cryonics providers that exist today and why they are unlike past failed efforts. Cryonics is a service that requires more than volunteer effort and you should expect to pay for it - an affordable amount if well planned, but nothing meaningful is free in this world. Like all services, you should look for a reputable provider who has been in the business for a while, has good references, and can point to pleased customers.

Growing Hair From Stem Cells (April 20 2009)
https://www.fightaging.org/archives/2009/04/growing-hair-from-stem-cells/
From the Daily Yomiuri, a short note on work aimed at tissue engineering new hair: a researcher "has succeeded in regenerating hair on mice using embryonic stem cells ... Yamaki extracted mesenchymal stem cells taken from the teeth of mice embryos and mixed them with mice embryonic stem cells, which form the basis of skin cells. The clumps resulting from the mix were then nurtured. It was later found that about 40 percent of the 48 clumps had one or two hairs growing from them. When protein, which quickens growth, is added, the hair growth rate increased to about 60 percent ... Hair growth was observed on all 12 mice that had the clumps implanted on their back muscles. Hair papilaries, which supply nourishment to the hair, also were found to have formed on the back muscle. ... If embryonic stem cells are combined with mesenchymal stem cells, which perform a number of other functions, a different organ can probably be created. The first thing I want to try to do is regenerate hair using human embryonic stem cells."

Regenerative Medicine For AMD (April 20 2009)
https://www.fightaging.org/archives/2009/04/regenerative-medicine-for-amd/
From the Times Online: "scientists have developed the world's first stem cell therapy to cure the most common cause of blindness. Surgeons predict it will become a routine, one-hour procedure that will be generally available in six or seven years' time. The treatment involves replacing a layer of degenerated cells with new ones created from embryonic stem cells. ... The treatment will tackle age-related macular degeneration (AMD), the most common cause of blindness. ... embryonic stem cells are transformed into replicas of the missing cells. They are then placed on an artificial membrane which is inserted in the back of the retina. ... Laboratory trials completed by the British team have demonstrated that stem cells can prevent blindness in rats with a similar disease to AMD. They have also successfully tested elements of the technology in pigs. ... the treatment would take 'less than an hour, so it really could be considered as an outpatient procedure. We are trying to get it out as a common therapy.' ... The clinical trial, due within two years, is expected to be the second in the world to use embryonic stem cells on humans. The first, on patients with spinal cord injuries, will start this year in America."

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