Several years ago, he gave up on life. He doesn’t know he gave up, but he did. This guy lives completely in the past. “Those were the good old days.” “What’s this world coming to?” Etc, etc. And he tells the same old stories over and over instead of experiencing new ones. He’s also drinking his way into an early grave

We have gone in opposite directions with our lives and have almost nothing in common outside of our history. Where I try to be present and future focused, he dwells on the past. Where I look forward to a long glorious future, he sees no hope. I’m long term optimistic. He’s not. Discussions with him are often painful, so I try to keep my distance and still remain friends.

Being his friend can be agonizing for two reasons. First, it’s sad to see someone you love give up and self destruct. I see little hope for his longevity… or happiness. But mainly, spending time with him is torturous. Everything you and I do, think about or say moves us towards our goals or away from them. Spending time with him is counter productive and even destructive. So why are we still friends? Well it’s a long story. But he was there 29 years ago when I really needed support. He’s the kind of person who would take a bullet for you. So it’s tough to discard him.

If there’s a lesson here, it’s this: Hang out with people who share your values and aspirations. Doing so is energizing. The opposite sucks your energy. And if we want to conquer the destructive effects of aging, we need all the energy we can muster. It’s a daunting task, and your survival may just depend on being at concert pitch as much as possible. I have pretty well insulated myself from most energy sucks, but not completely. It’s tough (at least for me) to sever relationships. But your happiness, productivity and longevity may depend on your willingness and ability to jettison your negative baggage. Unfortunately, that sometimes includes your relatives and even your spouse.

So you might consider at least scaling back negative relationships, thoughts and tasks in 2008 and replacing them with ones that will move you toward your aspirations. You only have 24 hours in each day. How you use them determines who you are and where you end up.

ON INEXORABLE TECHNOLOGICAL PROGRESS

A subtle and unresolved debate often rears its head within the healthy life extension community:

http://www.fightaging.org/archives/001378.php

"Many people see activism in support of longevity science to be of limited necessity because they believe, I think, that general advances in technological capabilities drive entrepreneurial development cycles that drive public support for new uses. In effect, this is a belief in the robustness of a free market to explore every possible economically viable avenue for human betterment, and to leap upon newly viable avenues as soon as they arise.

"My position is that this is probably the case in the long term. However, as always, it is easy to point out many economically viable and technologically possible projects that have not been started, in medicine or other fields, in the decades since they became viable. In addition to the economy of the free market, there exist economies of regulation, attention, understanding and philanthropic support - just because something is viable does not mean it will happen within your lifetime.

"There of course is the crux of the matter. If we are to benefit from healthy life extension therapies, from medical technologies capable of repairing the damage of aging, progress must be rapid. Healthy life extension through scientific advancement is inevitable - but not for us, unless we get our act together."

http://www.fightaging.org/archives/001314.php

What you have in common with naked mole-rats if you're lucky, that is: http://www.fightaging.org/archives/001382.php

"You might recall that different fatty acid or lipid composition in cell membranes was floated as a reason for the nine-fold longevity of naked mole-rats over related rodent species. Plenty of oxidative stress in the older mole-rats, but little sign of biochemical damage resulting from it - in comparison to those other rodents long since aged to death, that is.
Better, more damage-resistant building blocks down at the molecular level might be the cause. A forthcoming Rejuvenation Research paper discusses the results of a similar consideration of cell membrane differences and longevity within the human species."

It looks like some of the biochemical differences that may help naked mole-rats live so much longer than other rodents can also be seen in human biochemistry. According to this study, the descendants of people who lived to 90 and beyond tend to have cells that look more mole-rattish in their membrane construction than people of more short-lived families. It is fascinating to see real, structural differences down at the lowest level start to appear as a result of the search for the roots of human longevity.

An Old Acquaintance

posted on December 24, 2007

Last Monday I visited an old acquaintance. He is fairly famous… and very wealthy. He also has a passion for living a very long time. You might even call him an “immortalist”. I use that term loosely and prefer “indefinite youthful lifespan”

Discussions, negotiations and debates often break down simply because opposing parties have different definitions of many words. If we’d pause to make sure we understand each other’s definitions of key words, life would be sooo much easier. We assume we communicate because we speak the same language. But that assumption has cost many deals, friendships and marriages to go awry.

For example, one might call him or herself an immortalist, simply meaning they want to keep from dying from aging while realizing they would be susceptible to death from trauma. But their audience might interpret the term to mean living forever or eternally. Here again are two different words with similar nuances, both not representing what the speaker is trying to convey. Therefore the audience might dismiss them as a crackpot and miss the message that may extend their lives indefinitely.

On the other hand, the speaker might actually mean living eternally or forever. And maybe they might think they have a credible plan to achieve that. But that message would be much different, and their audience would be much smaller. Most people would dismiss them as a loon. So be careful with how you use words and with the words you use.

Now back to my acquaintance.

He is up in years and was pretty much resigned to not getting much benefit from tomorrow’s life extending technologies. But once he saw the illustration showing how a healthy 75 year old could potentially enjoy an indefinite youthful lifespan – and a description of the technologies that could deliver it to him – he seemed to grasp the implications of doing whatever it takes to stay alive long enough to benefit.

That was a great experience for me, not only because his particular life is worth saving, but because of his attitude shift. I learned how easily others could be convinced if approached the right way and educated. It also reinforced my belief that marketing these ideas to raise research funds is just as critical as the underlying science.

“Cryofeast”

posted on December 17, 2007

Saturday was full of life extension activities. In other words, it was stimulating and lots of fun.

Around noon, I had the opportunity to speak about extreme life extension to a new group of free market, health conscious “immortality” seekers. We had a lively Q&A afterwards and learned a lot about each other.

Then, I attended the S. Calif. “Cryofeast” at Peter Voss’ and Louise Gold’s home. Cryofeasts are annual gatherings of members of the cryonics community, other life extensionists, techies as well as a mix of other interested parties. As always, the food and drinks were great, and the conversations and catch ups with old friends were fascinating.

Generally speaking, life extensionists are my favorite people. They are typically intelligent, high achieving optimists. The key word is “optimists”. It’s just plain fun and energizing being around people with great attitudes, and especially those who love life and want as much of it as they can get.

The more time I spend on these activities, the more convinced I am we will obsolete death and deterioration from aging. And in your lifetime and in mine. It will take more than wishful thinking and positive attitudes though. It means lots of old fashioned brain sweating work. Just ask Aubrey de Grey.

On a similar vein, here is a collection of links and excerpts from the recent Cato Unbound debate on radical life extension:

http://www.fightaging.org/archives/001371.php

You'll find intelligent commentary on the Cato Unbound essays and reaction pieces out in the blogosphere too; Reason and I are always pleased to see growing discussion of the path to healthy life extension. Ongoing conversation, the broader the better, is a necessary foundation to raising support and building a better platform for research and fundraising.

http://www.fightaging.org/archives/001372.php

"If a technology existed to eliminate the physical effects of aging, it would be a boon to mankind, and it would be atrocious to forbid it. People should be allowed to experience aging if they wish, of course, but if science could make it optional, then the option should be available. And yes, I would take it. I would definitely want to live a thousand years or more. I would want all of my loved ones with me, and my only regret would be that some of them are already gone and cannot be. You and I are among the first of our species for whom physical immortality is even an outside possibility, but if the choice ever came up, I assure you that I would go for it."

PROGRESS REPORTS FROM THE METHUSELAH FOUNDATION

The Methuselah Foundation kicks off a newsletter series with an update on progress in Strategies for Engineered Negligible Senescence (SENS) research and development of the Mprize competition for rejuvenation science:

http://blog.methuselahfoundation.org/2007/12/methuselah_foundation_newslett_1.html

Tomorrow’s Extreme Life Extension Technologies

posted on December 9, 2007

These “bridges” could be the difference between you suffering and dying according to actuarial predictions… or enjoying an indefinite youthful lifespan.

I’ve often described how you can widen your window of opportunity to take advantage of tomorrow’s extreme life extension technologies. These “bridges” could be the difference between you suffering and dying according to actuarial predictions… or enjoying an indefinite youthful lifespan. Much is out of your control, but you have a choice to dramatically improve your odds.

The latest weapon in your arsenal is reading your genomic profile. Doing so could give you insights into what your particular genetic hazards are. Then you might be able to take steps today to reduce your risks. And get this. Experts in the field believe we could increase our healthy lifespans by at least 10 years with this tool.

Now here’s some really interesting news. Two companies provide this personal genotyping service for about $1000, 23andMe and Navigenics. See www.23andme.com and www.navigenics.com. There’s also a fascinating article in this month’s issue of Wired Magazine.

Do you remember my mentioning Ray Kurzweil’s Law of Accelerating Returns? That’s the law which illustrates the exponential rate of growth in technology as well as the decreasing cost of technology. Here’s a perfect current example of how powerful that concept is:

The Human Genome Project was completed in April, 2003 (two years ahead of schedule) for roughly $3 billion. Then in May, 2007, Dr. James Watson’s genome was sequenced for appx. $1 million. Then a mere four months later, Craig Venter’s genome was sequenced for $300,000. The X Prize will be awarded to the first to sequence 100 individual’s genomes for $10,000 each with an Oct., 2013 deadline. I’m betting someone cashes that prize in way before then!

This illustration dramatizes the impact the Law of Accelerating Returns will have on you, me and everyone else on this planet who decide to take care of themselves long enough to let radical life extending technologies to catch up to you.

SHORT VIDEOS BY AUBREY DE GREY EXPLAINING LONGEVITY SCIENCE

You may not have seen these short introductory videos before. Each briefly explains a single concept in longevity science, starting with some of the basic basics. They are the first in a new series of videos aimed at further bridging the gap between an overview for the layman and scientific publications:

http://www.fightaging.org/archives/001363.php
http://www.mfoundation.org/index.php?pagename=video_faq

Online video has been a tremendously success in broadening awareness and education for healthy life extension research, and the present state of science. This will continue to be the case, so pick out a few from the video FAQ page above, and forward them on to your friends.

Life Extension Opinions

posted on December 2, 2007

When will the future of healthy life extension medicine arrive? What is the likely shape of the near future of medical science? How do we usefully think about these things? Here are some opinions from Reason:

http://www.fightaging.org/archives/001362.php

"My view of the biotech and medical research field suggests that the development cycle for new products medians out at around a decade - a far cry from the rate of advance possible in less regulated industries, such as the development of computing devices. Calorie restriction mimetics look to come in under that median, while gene therapy is lagging far behind. Applications of autologous stem cell therapies look to fall somewhere in between. There are plenty of other examples if you care to go digging. The conservative late adopter waits for the second business cycle for any product he can afford to wait for. The second round is always better than the first, more effective, cheaper and more widely available."

From that viewpoint, there's plenty going on now that, if supported and encouraged, will blossom into highly effective technologies in the 2020s and 2030s. For example, the early 2030s will be likely be an age of routine mitochondrial DNA replacement. It will start in what is presently late middle age, an outpatient procedure that your physician will badger you into doing every couple of years. It'll be a pain to schedule, like the biopsies and exams, but skipping it will be like not checking for cancer - just dumb.

NOTE: In my opinion, we will have full age reversal capability by the early ‘30’s for those who can afford it and shortly thereafter for most with modest means. Also, due to the recent skin cell breakthrough coupled with at least one emerging atologous stem cell technology and one small molecule technology, I believe we will have impressive therapies which won’t require excessive regulation within five years

Wild Eyed Optimist Over Indefinite Youthful Lifespans

posted on November 25, 2007

Admittedly, I’m a wild eyed optimist, especially regarding the prospects of indefinite youthful lifespans for you and me. But since I KNOW I’m an optimist, I try to take special efforts to see and understand pessimists’ points of view. Ten I try to balance the input and come to my own conclusions. In other words, I try to be objective about what our chances really are. I sent you my timeline and budgetary estimates several issues ago and stand by them.

So here’s an opinion from one who may be the most pessimistic of all well known gerontologists, followed by Reason’s commentary:

http://www.fightaging.org/archives/001354.php

"'We're all going to croak,' says Richard Sprott, the Ellison Medical Foundation's director, who expects that humans may eventually live as much as 30 years longer, but only in the distant future."

Read the full post; I find it incredible that anyone with Sprott's background can stand in the midst of the present outright revolution, of wild, foaming progress in bioscience, and say that things just aren't going to change all that much. It's an outlandish position - and an outlandish position held by someone who directs a fair amount of funding for aging research:

http://www.fightaging.org/archives/001331.php

It's a sad state of affairs we're in, wherein so much of the research establishment has declared defeat and stasis before even setting goals for aging science. How is it that we have an establishment community disbursing so much in the way of funds to exactly the people who are not going to make significant progress - those who say that progress is impossible or far distant in advance of any initiative?

The advance of science and technology is change itself, is the growth of opportunity and choice, and is the opening of new doors in the halls of the human condition. The hidebound and defeatist are not really contributing - if you want things done, if you want bold new progress, fund the people willing to set goals and shake trees.

NOTE: Sprott’s stance makes we want to toss my cookies. Everyone is entitled to an opinion. In his case though, I believe it will cost lives. Lots of lives. I say that not only because he may control more of the scarce “life extension” funding than almost all the administrators and researchers in the free market combined… but also because he is influential. With 100,000 people dying every day from aging, the last thing we need is anyone standing in the way of those who refuse to “go silently into the night”.

If someone were drowning and a lifeguard stood in the way of a would-be rescuer, what would you call the lifeguard? Multiply that my millions.

Longevity Workshop

posted on November 19, 2007

Last Friday energized me for almost three days… and counting.

Dr. Aubrey de Grey was in Los Angeles, and we cosponsored a Longevity Workshop. Of course Aubrey spoke brilliantly about the Methuselah Foundation and SENS and how it will reverse aging. www.sens.org

Dr. Stephen Coles opened the workshop with a Gerontology Research Group presentation. See www.grg.org for some fascinating life extension info.

The eminent evolutionary biologist Dr. Michael Rose followed Aubrey with a broad overview of how his 30 years of research is finally paying off in diagnostic tools and nutraceuticals that promise to have a huge impact on aging in the very near future. www.biology.ucr.edu/irpee/index

Then I chipped in by describing Maximum Life Foundation’s strategy to reverse aging in 21 years.

Finally, we had a lively panel discussion which included Peter Voss. Peter founded and manages Adaptive AI. See www.adaptiveai.com. Adaptive AI is aggressively pursuing Artificial General Intelligence (AGI). Once developed. Imagine the positive impact AGI, or machines with human level thinking abilities would have on life extension research!

So why am I so pumped up over info that you would think is old hat to me? Simply because just being around committed positive life extensionists supercharges me. And I don’t just mean the presenters. I mean people like Bruce Klein, founder of the Immortality Institute www.imminst.org and his wife Susan who spent so much time organizing this event. Bruce now works with Ben Goertzel in another AGI company called Novamente www.novamente.net. And I especially mean the enthusiastic audience, nearly 100% devoted to the prospect of indefinite youthful lifespans.

Afterwards, the speakers and organizers met for a dinner/social function hosted by super nice guy Elon Musk. Elon co-founded PayPal. His former partner, Peter Thiel, donated $500,000 to the Methuselah Foundation and ledged $3 million.

Actually, I’ve been energized for over two weeks. You almost always get positive feedback when you preach to the choir. No endless questions regarding what we’re going to do with all the people or how unnatural this is, etc. But a couple of weeks ago, I spoke to about 700 small business owners at a marketing conference. My topic was supposed to be the philosophy of certain success principals, but I spent about as much time on extreme life extension. Five years ago, an uninitiated audience like this would have thought I was a fruitcake. But of the 150 or so people who approached me afterwards, over half were as interested in the prospect of open ended lifespans as they were about marketing and business success.

Exhilarating!

There’s more good stuff, but I’ll save it for later. Here’s this week’s longevity info from the Longevity Meme:

REPORTS FROM THE 2007 HILLBLOM FOUNDATION MEETING

Aging researcher and science blogger Chris Patil has been on the meeting trail of late. The past week, he has posted reports from the 2007 Hillblom Foundation scientific meeting. The Larry L. Hillblom Foundation funds mainstream aging research taking place in California, including the lab of Cynthia Kenyon. You'll find links and quotes in this Fight Aging! post:

http://www.fightaging.org/archives/001350.php

Along the way, Patil provides an excellent summary of the viewpoint and status of the presently dominant approach to longevity research - engineering greater longevity through genetic and metabolic manipulation:

"Given that genetic manipulations have revealed significant plasticity in the rate of aging, shouldn't we be able to discover drugs that phenocopy, simulate or even outstrip the effects of longevity-extending mutations?
Thus far, early screens for both stress resistance and lifespan extension per se have generated several lead compounds that delay aging in yeast, worms and flies (and in at least one case, both species). Studies from multiple labs are beginning to converge, with the ultimate goal of testing multi-species hits in mouse models of aging and age-related diseases. In closing, Lithgow acknowledged that understanding of the mechanism of action of these compounds is lagging behind their discovery, in part because some of the most promising molecules have mystifyingly large numbers of candidate targets."

By now you probably all know that Reason considers metabolic engineering to slow the rate of cellular and biochemical damage of aging to be a poor, second best path in comparison to developing methods to repair that damage. A good summary as to why that is the case can be found here:

http://www.fightaging.org/archives/001024.php

NOTE: Michael Rose may be way ahead of the curve here. Stay tune

Recent Age-Breaker Research

posted on November 5,2007

Advanced glycation endproducts (AGEs) are a range of metabolic byproducts that gum up the works in your biochemistry, such as by sticking vital chemical compounds together so that they can't perform their role. The more AGEs in your system, the worse the damage they cause, directly contributing to age-related degeneration and disease:

A number of groups are at the stage of animal or early human trials with designed or discovered compounds, many focused on diabetes due to the increased level of AGEs associated with that condition, and the fact that regulatory agencies do not recognize aging as a disease - and thus will not approve a therapy designed to repair a cause of aging. For example, the AGE-breaker compound C36 has been evaluated on diabetic rats:

"Unfortunately, past evidence suggests that excitement over work in rodents should be muted at best - the history of ALT-711 or alagebrium demonstrates that different types of AGEs are important in shorter-lived mammals versus humans. So far, promising work in mice and rats has translated poorly into human therapies - in most cases, through trying to address the wrong AGEs."

New Calorie Restriction Reearch

posted on Ocotber 28, 2007

You'll see a couple more articles in the news and headlines section of this newsletter: eating fewer calories while retaining essential nutrients helps to maintain the number of dopamine receptors, reduce visceral fat, reduce inflammatory cytokines, maintain muscle mass, and enhance DNA repair mechanisms.

http://www.longevitymeme.org/news/view_news_item.cfm?news_id=3389
http://www.longevitymeme.org/news/view_news_item.cfm?news_id=3390
http://www.longevitymeme.org/news/view_news_item.cfm?news_id=3392

As time goes on, researchers will provide more and more specific accounting of how it is that the practice of CR slows aging - slows the rate of change and damage in our fundamental biochemistry, in other words - and thus extends healthy life span. These are all small pieces of the larger puzzle, as is this item on stem cells and CR noted at Fight Aging!:

http://www.fightaging.org/archives/001333.php

"[Blood stem cell] numbers are highly variable in [aged mice], however, the observed loss of marrow function is due to a major loss in repopulating ability per [stem cell]. [Calorie restriction] greatly ameliorates this loss of function with age."

Our stem cells are key to the repair of damaged tissue and maintenance of function in healthy tissue. They may also be a key to cancer, via damaged cells run amok, hence evolution has produced a system of stem cells and stem cell niches that winds down its activities with age and increasing biochemical damage. It shouldn't be a surprise by now to find yet another well-known decline in our biology that is slowed by CR.

If you want to learn more about calorie restriction, a good place to start is the link below. Note the litany of other health and biochemical improvements uncovered in research over the past few years:

http://www.longevitymeme.org/topics/calorie_restriction.cfm

The Prospects for Enhancing Autophagy

posted on October 21, 2007

Casual deathists are everywhere. I'm sure you all know someone who responds to the concept of healthy life extension with "I can't see why anyone would want to live past 100." This is what they have been taught throughout their lives, implicit in the way their peers and parents plan, act and talk. Perhaps "learned deathism" is a better term. A longevity revolution is right around the corner, yet we structure our lives in the same way our grandparents did:

There's nothing wrong with choosing not to strive for more healthy life, but I believe it's our responsibility to at least point out the lazy assumptions and false information that forms the basis of most casual deathism. Kevin Perrott, organizer of the Edmonton Aging Symposium, recently did a sterling job of this in a letter to the Globe and Mail, reproduced in this Fight Aging! post:

http://www.fightaging.org/archives/001332.php

THE PROSPECTS FOR ENHANCING AUTOPHAGY

Autophagy is the process by which damaged cell components are broken down to be recycled - a form of maintenance in the dynamic machinery of your body. Present evidence indicates increased autophagy to be one root of the health and longevity benefits provided by calorie restriction. More active maintenance should in theory mean fewer damaged components creating lasting harm in the cellular environment:

Scientists are now beginning to manipulate levels of autophagy independently of calorie restriction to establish the prospects for therapies:

http://www.fightaging.org/archives/001329.php

"As an application, intensification of autophagy, by the administration of antilipolytic drug, rescued older cells from accumulation of altered [mitochondrial] DNA in less than 6 hours. It is concluded that the pharmacological intensification of autophagy [has] anti-aging effects and might prove to be a big step towards retardation of aging and prevention of age-associated diseases in humans."

Damage to mitochondria - and their DNA, separate from that in the cell nucleus - is of particular importance. The following Fight Aging! post outlines how a comparatively small number of damaged mitochondria, your cellular power plants, could lead to widespread damage and degeneration throughout the body:

http://www.fightaging.org/archives/000994.php

Safe repair of mitochondrial DNA is a big deal, however it is accomplished, as is the sight of ever more researchers writing openly about the defeat of aging

Business Building and Development Conference

posted on October 14, 2007

I wish you could have been with me last week. Please let me explain…

I attended a week-long conference for two reasons. First, my assistant went on his honeymoon then, and it was convenient for me to hole up and rest in a hotel for 5 days. Second, it gave me a good chance to spend some time with some friends who I hadn’t seen for a while. Oh and there was a third reason too… I figured I couldn’t help but pick up a nugget or two of valuable information.

Well, here’s what happened:

I didn’t get much rest. The conference started at 9 am each day and ran until almost 8 pm. And it was so captivating that I didn’t want to miss a word.
I hardly got to spend any time with my friends (See #1).
I picked up my nugget or two in the first 10 minutes. Five days and a whole tablet full of notes later, I looked back on the most insightful and valuable conference I ever attended.

Without going into detail, it was advertised as a business building and development conference. The organizer, Eben Pagan, walked nearly 200 attendees through the trials and tribulations he endured in building his business (and his incredible life) and how to shortcut them. Eben disclosed, step-by-step, how he built a business that triples every year. It already earns well over $2 million a month – and is still exploding. But there was more. Much more.

Why do I mention this in a life extension newsletter? Because solving the aging puzzle and delivering extreme life extension to you is as much a business and marketing challenge as a scientific one. Last week’s education is fast tracking that challenge for me. It could do the same for you, your project or your business.

If you’d like details, go to http://getaltitude.com

The Cost of Aging Illustrated

posted on October 8, 2007

The Milken Institute has provided another window into the staggering cost of aging with their latest work, focused on the economic cost of chronic disease:

http://www.chronicdiseaseimpact.com/
http://www.fightaging.org/archives/001321.php

"Take a look a look at the major categories of chronic disease examined in the report website - almost all are age-related conditions. The greatest correlation for suffering chronic disease and associated costs is with age, with the toll of cellular and biochemical damage established across a lifetime of metabolic activity. But aging is always the elephant in the room when you're looking at the work of those close to the regulators.
Obvious, behind all the facts and figures, and absolutely unmentioned. That has to change if progress is to be made."

“The Choice of Living a Healthy, Youthful Life of Centuries and More is Inevitable"

posted on October 1, 2007

Death is NOT the natural order of things. Overcoming death is.

For conscious intelligent beings, indefinite life eventually becomes the natural order.

Every life form fights for survival. But until now, there was no hope for avoiding decay and death. In my humble opinion, the purpose of life is simply to keep on living, growing and thriving. Only with human intervention can we overcome death and achieve this. We humans, as an intelligent conscious species, finally thought our way to the threshold of open-ended life spans. Without intervention, every life form is doomed to personal oblivion. Evolved beings will always figure out how to survive.

I think about this a lot including Sunday afternoon a week ago when I attended an intimate discussion/brainstorm session. Some of my very favorite people were there. There were also some equally impressive quality people who I met for the first time. During the conference, and during discussions later with mostly new friends, I couldn’t help thinking about how they deserve to live indefinitely… and that our efforts just might insure they do. This was partly selfish of me, because I want open-ended time to develop new relationships with these fascinating people.

A common objection to living an unusually long time crossed my mind as well. It usually goes something like “I wouldn’t want to outlive all my friends”. This deathist phrase, at least to me, is the most illogical and idiotic reason for a death wish. First, if when we have a choice, and your friends choose to die, why would you let them drag you along? Second, if I can find some potentially cherished new friends in one afternoon, how many new friends do you think you could make in several more lifetimes? Granted, this was a select group that I was with a week ago. But they are certainly not the only interesting people in the world.

By the way, I didn’t hear anything but enthusiasm about the prospects for extreme longevity from this positive group.
________________________________________________

DNA DAMAGE AND TARGETING MITOCHONDRIA

"Does the accumulation of DNA damage in the cellular nucleus contribute to significantly to aging? How, if so? It is a topic for debate, with a weight of papers behind many of the consensus interpretations, but most of the community would answer 'yes' with some variety of qualifications. It isn't hard to find academic arguments for the role of DNA damage in most of the better known age-related degenerations. It's a matter of time, resources for research and scientific debate as to which pan out."

It is accepted that cancer is a consequence of DNA damage, but the relationships of other aspects of degenerative aging to accumulated mutations in our nuclear DNA are much argued. Is declining stem cell capacity with age caused in part by DNA damage, for example? A good question - and one that has yet to be answered in any firm manner.

Let's move on to your other DNA, contained in mitochondria, the power plants of your cells. Originally symbiotic bacteria, and now a vital cellular component, mitochondria have retained the functional portions of the ancient DNA they brought to the party. The weight of evidence for a connection between damaged mitochondrial DNA and aging is much greater than for nuclear DNA, and researchers are far closer to being able to do something about it:

"Your mitochondria are a source of a whole lot of biochemical trouble as the years go by. Damaged mitochondria proliferate in some cells and, like damaged factories, pollute the cells with excess reactive oxygen species and free radicals produced as metabolic byproducts. Each damaged cell then tries to maintain itself by exporting more reactive oxygen species and free radicals from its cell membrane structures, spreading the damaging pollution far and wide in the body. Repairing or replacing damaged mitochondria is one way to strike at the root of this process, and a number of groups are working on that. The SENS research program identifies a different and even more fundamental way forward: create a backup in the cell nucleus for specific mitochondrial processes that cause all these problems when damaged."

"Another approach that's out there in the field is to target antioxidant chemicals to the mitochondria, where they can be effective in soaking up some fraction of the excess free radicals before they wreck havoc.
Antioxidants in general don't seem to be terribly effective when simply thrown at our biochemistry. While making a difference, targeted antioxidants are clearly only a delaying tactic - as opposed to repair strategies that can be performed indefinitely. This is what medicine looks like at the base layer these days - a lot of organic chemistry, building molecules that tweak other molecular machinery in a particular way. Manipulating mitochondria to reduce their contribution to aging and age-related disease is a growth field; you'll be seeing a lot more of it in the years ahead."

A THOUGHT FOR THE DAY ON AGING

"Brain aging is gradual brain damage. Some people think aging is wonderful and natural. That's tantamount to saying that brain damage is wonderful and natural."

Aubrey de Grey’s SENS Conference

posted on September 16, 2007

We’re seeing some serious progress in life extension research. Here are two projects that were announced at Aubrey de Grey’s SENS Conference last week:

http://blog.methuselahfoundation.org/2007/09/sens3_report_towards_mitochond_1.html

"Unlike most other parts of the cell, mitochondria house many of the genes encoding their essential proteins within themselves. These genes are vulnerable to the constant assault of free radicals produced by the mitochondria as a side-effect of their role as cellular power plants. When mitochondrial DNA is damaged, it cannot make the proteins needed to carry on the essential business of generating energy for the cell; the ensuing metabolic damage is the driver of age-related rise in oxidative stress. This oxidative stress fuels free radical damage and interferes with essential signaling pathways in cells far from the original site of the damage.

"PhD candidate Mark Hamalainen of Cambridge University presented the initial success in his Methuselah Foundation-funded work on allotopic expression, showing evidence that his allotopically-expressed genes could encode the relevant proteins and that these were taken up into the mitochondria. In this case, the genes encode healthy and defective versions of the protein that is miscoded in Neuropathy, Ataxia and Retinitis Pigmentosa (NARP), a hereditary mitochondrial disease characterized by blindness and weak and uncoordinated muscles. Well done! It is good to see Foundation-funded research make such solid progress; many thanks go to the generous donors who have made this possible."

http://blog.methuselahfoundation.org/2007/09/sens3_report_the_gift_versus_c_1.html

"In 2003, Dr. Zheng Cui and his colleagues at the Comprehensive Cancer Center of Wake Forest University reported the discovery of mice with immune cells that rendered them invulnerable to cancer. Last year, Dr. Cui electrified the world when he showed that the new strain's cancer-fighting abilities were caused by a particular subset of their immune cells -- members of a class of white blood cell known as neutrophil granulocytes. These cells are from the innate immune system, meaning that they don't have to 'learn' to identify a narrowly-defined enemy, but are constantly on the lookout for broadly-defined 'foreign' cells.

"At SENS3, Dr. Cui presented the next logical step in his research: work demonstrating the existence of, and characterizing, high-potency cancer-killing granulocytes in humans."

Ending Aging

posted on September 10, 2007

Death is NOT the natural order of things. Overcoming death is.

For conscious intelligent beings, indefinite life eventually becomes the natural order.

By the way, I didn’t hear anything but enthusiasm about the prospects for extreme longevity from this positive group.
________________________________________________

DNA DAMAGE AND TARGETING MITOCHONDRIA

A THOUGHT FOR THE DAY ON AGING

"Brain aging is gradual brain damage. Some people think aging is wonderful and natural. That's tantamount to saying that brain damage is wonderful and natural."

Longevity Mutations Keep Rolling In

posted on August 12, 2007

Saturday evening, I enjoyed life extension and stem cell technology conversation and dinner at an incredible couple’s home. Their guests were incredible as well. Not only were they bright, well informed and enthusiastic about extreme life extension, but they were a mix of savvy and successful scientists and business people. The latter will have as much to do with your longevity as the former. Maybe more. You’ll see what I mean when you read the attached PowerPoint.

Since 2000, Maximum Life Foundation designed a scientific and financial roadmap to reverse the human aging process. The attachment illustrates an aggressive approach to solving aging in your lifetime. You’ll notice what a surprisingly small investment we think it will take. But we can back up our scientific and financial assumptions. Now it’s time to implement the plan.

LONGEVITY MUTATIONS KEEP ROLLING IN

Biomolecular researchers have been hitting their stride in recent years. At least half a dozen methodologies are now demonstrated to extend healthy life span in mice by 30-40%, all based on tweaking the operation of core components or systems of metabolism. Here's the latest, another single gene alteration.

http://www.fightaging.org/archives/001282.php

"Genetic deletion in mice of pregnancy-associated plasma protein A (PAPP-A), a recently identified metalloproteinase in the insulin-like growth factor system, extends by 30-40% both mean and maximum lifespan with no reduction in food intake or secondary endocrine abnormalities. Furthermore, these mice have markedly reduced incidence of spontaneous tumors."

Fat to Inflammation Related Disease

posted on July 30, 2007

Scientists continue to fill in the gaps remaining in understanding how fat leads to inflammation, which in turn accelerates many of the most common age-related conditions. Being overweight appears to shorten the range on your healthy life span by increasing the rate at which biochemical and cellular damage accumulates:

"In recent years, the immune system has also been implicated in type 2 diabetes - in particular imbalances in cytokines, an immune system component that causes inflammation. Macrophages appear in high concentrations in fatty tissue. With funding from the National Institutes of Health, Nadler has traced the mechanism by which the presence of large numbers of fat cells stimulate the macrophages to activate the 12/15-LO gene, and has documented the cascade of inflammatory reactions that results. He has found that the 12/15-LO gene produces two proteins that convert fatty acids into cytokines."

A chain of consequences: more body fat means more macrophages in fatty tissue, which means more cytokines, which means more inflammation. More inflammation brings much greater risk of Alzheimer's, diabetes, heart disease and other more general forms of age-related degeneration. That risk is based upon the greater accumulation of age-related changes in your biochemistry - damage, in other words.

While science will advance to wondrous new heights in the decades to come, it only makes sense to play the odds, take care of the health basics, and increase your chances of living healthily into the era of rejuvenation medicine. We're not there yet, the longevity research community to rival the cancer establishment has yet to be built, and we're all still aging - but most of us are lucky enough to have some modest choice as to how fast degeneration takes usBack to Top

A Deliberately Provocative Question

posted on July 23, 2007

If you knew technologies over the next few decades could deliver to you a chance for an open-ended youthful lifespan, how much would you donate to the research?

Say you want to live a much longer, healthier life. Would you help to achieve that goal by donating 90% of your net worth in support of research? If so, when? When you are terminally ill when it would probably be too late? Years or decades down the road? How about now? If not, how much?

There are no right answers in consideration of personal economic choices, but these are question you might ask yourself. Wealth at any level is worthless to the dead, and being alive and healthy allows you to generate more wealth. Logically we should all be willing to devote most of our net worth to longevity research at the most effective time. If we can buy time with money - and we can begin to now in earnest, for the first time in history, by supporting the research that will lead to the first healthy life extension medicine - then we should all be in that market.

MaxLife believes the tiniest fraction of most wealthy individuals’ net worth or annual income could reverse aging in less than 30 years. It also believes most of the money could be invested… not donated… in for-profit enterprises. More on this topic in a week or two.

Core Human Ideal

posted on July 9, 2007

To seek to provide the choice of healthy longevity for all who want it is an aspect of the better side of human nature:

http://www.fightaging.org/archives/001254.php

"Helping to make life longer and better, one action at a time, is a core human ideal. There are no special cases, no magical transition point at which it's fine and dandy to write people off or justify their deaths.

Healthy life extension flows quite naturally from the same mindset that helps neighbors and appreciates modern medicine. We all recognize that which is unpleasant in commonplace life, and it's only natural to work to remove that unpleasantness. Seeking equality of opportunity by helping people to overcome the limitations of their own personal human condition is a worthy goal today, and will be just as much so in a future of far greater opportunity. The foundation of opportunity is life - is being alive, and possessed of the vigor to take advantage of that fact. Without that, there is nothing. So I think we really have to start there, with aging, a great injustice blindly inflicted upon humanity by chance, physics and evolution.

To not seek the cure for aging would be just as strange as to fail to seek a cure for cancer or Alzheimer's - it would be inhuman and unnatural for the species that helps its neighbors and appreciates the good things in life."

Repairing Mitochondria to Help Thwart Aging

posted on July 2, 2007

66 year old Dr. Stephen Coles, co-founder and president of Gerontological Research Group http://www.grg.org has apparently discovered the Fountain of Youth.

Last Saturday, Dr. Coles married a beautiful 26 year. Congratulations to Steve and Natalie. I will make sure we all get invited to their Golden Anniversary celebration.

REPAIRING MITOCHONDRIA TO HELP THWART AGING

Mitochondria are the power plants of your cells, evolved from symbiotic bacteria and bearing their own DNA. They transform food into the molecule ATP, used by cellular processes for energy, but mitochondria and their DNA become damaged and mitochondrial function declines with advancing age. As more is discovered and the tools of modern biotechnology improve, the repair of damaged mitochondria as a strategy to help halt or reverse aging looks ever more plausible with each passing year.

In recent months, some researchers have suggested that ongoing decline in mitochondrial function is the cause of two other biochemical processes linked with aging and specific age-related conditions. Firstly, that shortened telomeres rest on mitochondrial damage:

http://www.fightaging.org/archives/001204.php

Secondly, that declining ability to repair DNA damage also might have the same root cause:

http://www.fightaging.org/archives/001249.php

Both DNA damage and telomere shortening are widely considered to contribute to age-related degeneration - as for so much of aging science, definitive mechanisms and absolute answers are still up for debate, however. Neither of the "mitochondria did it" proposals above has yet had time to be widely debated and further investigated, but this is not to mention the direct role of mitochondrial DNA damage in causing age-related degeneration in the well-supported mitochondrial free radical theory of aging:

http://www.fightaging.org/archives/000994.php

A successful strategy to defeat aging - defeat, not just slow - must look at the biochemical changes that occur with aging, treat those changes as damage, and repair them. We shouldn't follow the cues of past decades and merely aim to patch over the symptoms of aging, or merely aim to slow aging, as that is an expensive way of failing. The more researchers understand our biochemistry, the better they can identify which age-related changes are truly fundamental - to strike at the root, with less effort and more rapid results. But as for the bridge builders of past millennia, we don't necessarily need complete understanding to start now and produce good work:

http://www.fightaging.org/archives/001047.php

It will be fortunate if mitochondrial damage turns out to be a more important root cause of aging than previously thought, as scientists have already created technology demonstrations for a variety of ways to repair that damage... or make it irrelevant. In the latter category are efforts to move fragile mitochondrial DNA - genes - into the well-protected cellular nucleus. These efforts received a boost with recently published work:

http://www.fightaging.org/archives/001248.php

"The job of a gene is, in essence, to act as the instruction set for the production of proteins, the components of cellular machinery. A core problem in moving the factory from the mitochondria to the nucleus is that these proteins would then have to struggle their way back to the mitochondria where they are needed; this has been a challenge for a variety of reasons.

"These researchers have demonstrated a way to overcome that challenge for at least a subset of mitochondrial genes - via what might be viewed as a rather clever hack to the programming of the cell - and thus can repair dysfunctional mitochondria which results from damage to those genes and a local absence of vital proteins."

Pay attention to the work taking place in laboratories today and tomorrow - medical science is the future of our healthy longevity.

Striking Back at CYTOMEGALOVIRUS

posted on June 25, 2007

We are on the cusp of extreme life extension. In fact, you may outlive degenerative aging and disease as we know them. But you may not. Whether you do or not is partially up to you.

Unfortunately, your friendly regulatory agencies may have a say in your destiny as well. Current and pending legislation may rob you of your chance. Since any little breakthrough - or bottleneck - could be the difference between your life and death, let your friends and contacts know that Health Freedom needs their help right now.

You can send 5 friends information about this opportunity. Or you can send it out to your entire address book by cutting and pasting the information (or sending the link) with a short message in your own words asking them to send an electronic letter to their Congressperson and forward this information to their circle of influence as well.

Thanks for your activism and thanks for taking the time to let everyone know that health freedom needs their protection.

Take easy action now at:
http://www.democracyinaction.org/dia/organizations/healthfreedomusa/campaign.jsp?campaign_KEY=11754&t=

STRIKING BACK AT CYTOMEGALOVIRUS

If you don't know what cytomegalovirus (CMV) is doing to you and everyone you know ... well, time to find out. A great deal of the deterioration of the immune system with advancing age is due to CMV:

http://www.fightaging.org/archives/001247.php

"CMV doesn't really hurt you at all in the short term; most people don't even show symptoms. But because you cannot clear it from your system, its presence chews up more and more of your limited immune resources with time. This is what happens to all of us with increasing age, speeding the downward spiral: if your immune system isn't up to snuff, you're that much less able to resist further damage."

Scientists are making progress in developing a vaccine, however - which is good for those of us not already damaged to the hilt:

http://www.eurekalert.org/pub_releases/2007-06/uoc--nvp062207.php

"Using a two-pronged approach, we successfully created and tested a vaccine in a mouse model with CMV that shows enormous promise for re-directing the body's immune system, enabling it to fight the virus."

For those with significant damage to the operation of our immune system, more adventurous medical technologies will be required - reconfiguring our immune systems by destroying the wrongly specialized cells, for example, or forcing the body to completely recreate the immune system from scratch. Fortunately, researchers are moving through the early steps on that path also:

http://www.longevitymeme.org/news/view_news_item.cfm?news_id=3017

"Revimmune works by temporarily eliminating peripheral immune cells ... stem cells uniquely have high levels of a particular protective enzyme that can be measured in advance of therapy, which makes them impervious to Revimmune, and allows the surviving stem cells to give rise to the new immune system over 2 to 3 weeks."

Ray Kurzweil Article

posted on May 28, 2007

Did you happen to read the Ray Kurzweil article in the May issue of Fortune Magazine? If not, it’s 8 pages of inspirational reading.

Go to: http://money.cnn.com/magazines/fortune/fortune_archive/2007/05/14/100008848/

Ray is one of the world’s leading visionaries. Through his discovery of the Law of Accelerating Returns (LAR) and all the media coverage he gets, Ray may trigger the tipping point that launches the idea of extreme longevity from a fringe idea to a universally accepted one. Once that happens, the investment floodgates should burst open, and naturally terminated lifespans as we know them will become history.

The LAR is controversial and hotly debated in some circles. But in my mind at least, it is logical and crystal clearly illustrates what the future holds for us. In fact, I base almost all my arguments for extreme longevity in our lifetimes on the LAR.

I mentioned it before, but it bears repeating. It’s too important an idea to gloss over. In a nutshell, here it is:

The Law of Accelerating Returns
After years of study and thousands of calculations, Ray developed the LAR. Many believe the effects of his law will change your life in more ways than any other single idea in the world.
He observed that the rate of change itself is accelerating. This means the past is not a reliable guide to the future any more. The 20th century was not 100 years of progress at today’s rate, but rather was equivalent to about 20 years, because we’ve been speeding up to current rates of change. And, we’ll make another 20 years of progress at the year 2000 rate, equivalent to that of the entire 20th century, by 2014. Then we’ll do it again by 2021… and so on.
Because of this exponential growth, the 21st century is projected to achieve 20,000 years of progress at the rate of progress we saw in 2000. That’s 1,000 times greater than what we witnessed in the entire 20th century, which in itself was a mind-boggling century of growth.
Exponential growth can be very seductive. You barely notice it at first. But before you know it, it virtually explodes.
For example, let’s say you start with one grain of sand and double it every day. After 5 days, you’d have 32. Hardly noticeable. In 5 more days, you’d have 1024. Well that’s more, but not even a teaspoon full. In 10 more days, you’d have over a million. 10 days after that you have 1.1 billion. And the next day, 2.2 billion. Five days later, you’re up to your neck in 53 billion grains of sand. The 1st 5 days took you to 32. Now, in one day, you’re choking on 53 billion extra grains. The next day on an additional 106 billion.
This is EXACTLY what’s happening today with knowledge and technology. You hardly notice the growth at first. Just like with cancer research so far. Then suddenly it seems to explode. This is why life extending technologies and cancer and heart disease technologies, which seemed to be advancing agonizingly slow, are about to go into hyperdrive. And that’s why taking steps to extend your life now are going to be infinitely more important to you than they’ve been in the past. Before some of us know it, extreme longevity will be upon us.
Others will miss the boat
Ray alone can’t save you or your loved ones. Neither can Aubrey de Gray, artificial intelligence, nanotechnology or Maximum Life Foundation. You alone can maximize your chances. Some of the things you can do today can give you an extra 5-10 or more years of healthy life. They may seem boring, not worth the effort or even too simplistic. These simple steps better position you to be here when the pending explosion of knowledge delivers humanity amazing life extending capabilities. Go to http://maxlife.org/ownersmanual.pdf and download SALADS™. You’ll have in your hot little hands a treasure of information that can help you bridge the gap between now and tomorrow’s life saving technologies.
You can do more. No man is an island. Achieving extreme healthy lifespans is going to be a team effort. The more you contribute, the better your chance. At a minimum, I encourage you to help spread the meme. Forward this newsletter to your associates who may have an interest.

You might consider lending some of your time and talents to some of the companies pursuing health and life extending pursuits as well as to Methuselah Foundation and Maximum Life Foundation. Every bit helps. Finally, consider investing in some of the companies devoted to your health and longevity… as well as donating to Methuselah or MaxLife.

Commentary From Reason

posted on May 22, 2007

"Once you start to make this comparison between the cost of degeneration and other goals that could be achieved with the same use of resources, it quickly becomes clear that the level of resources we direct as individuals to medical research is low to the point of irrationality."

If you take a closer look at the staggering numbers, it quickly becomes apparent that no level of investment in healthy life extension research - that could plausibly be attained by the human race - could ever be too much. The level of destruction caused by aging dwarfs that of global wars, and yet we are blind to it, because it is constant and omnipresent.

Some avenues of medical development for the next decade or two are foregone conclusions: now obvious, planned and underway. This known technology in waiting is impressive, even without considering the impact of unforeseen new discoveries. To pick one example:

http://www.fightaging.org/archives/001219.php

"The use of biodegradable guide materials in conjunction with signaling chemicals is in the very first stages today, but I'm sure you can see just how sophisticated this could quickly become. For example, the growth of entire organs or complex tissue can be envisaged: researchers a decade from now will use rapid prototyping technologies to build three-dimensional guide material frameworks, layered with chemicals known to produce the right growth and cellular differentiation characteristics, and add stem cells to get the job started. These initiatives and technologies exist today at varying stages of progress and sophistication ... Regeneration of bulk parts and replacement of damaged tissue is not rejuvenation, but it should lead to a fair degree of healthy life extension. If life extension of 10 to 20 years is plausible from a simple extrapolation of systems biology, then a far better control over regeneration should add to that. It certainly won't hurt our prospects."

Beginning Anti Aging

posted on May 14, 2007

American Heritage Dictionary defines “meme” as a unit of cultural information, such as a cultural practice or idea, that is transmitted verbally or by repeated action from one mind to another.

We help spread the longevity meme through this newsletter, a synopsis of Reason’s “Longevity Meme Newsletter”. See www.longevitymeme.org for full texts.

ENDING AGING

There is nothing wrong with becoming old. There is everything wrong with becoming frail and sick. The future I'd like to see is one in which "old" is all upside - experience and wisdom without decrepitude and death. The forthcoming "Ending Aging" is a book that explains the best course we can presently chart to that end:

http://www.fightaging.org/archives/001206.php

"Aimed squarely at folk who want to know more about the science of repairing the molecular damage that causes aging, but find navigating the wild waterways of scientific publications too intimidating or time-consuming, this is a step by step, detailed explanation of how we could achieve radical life extension within our lifetimes, as best we understand from our present knowledge of our biochemistry.

If you're used to the 'eat this, take supplements and exercise' longevity bookshelf, Ending Aging is a big step up - very much more 'research this science to develop this specific therapy based upon that sound basis established over the past two decades.' You'll be seeing more of that in the years ahead, and this exactly where your attention should be focused if you care about your own longevity."

Milken Global Conference

posted on May 10, 2007

I attended the Milken Global Conference this week (That’s why I’m late with this newsletter). Over 3000 people attended including the world’s leading decision makers. It featured such luminaries as Sumner Redstone, Rupert Murdoch, Steve Wynn, Bill Frisk, Steve Forbes, Ted Turner, Boone Pickens, Arnold Schwartenegger, Roger Ailes, Andre Agassi, Michael J. Fox, Sally Ride, William Bennett, John Kerry, Lowell Milken, Sydney Pollack, 7 Nobel Laureates and of course Michael Milken.

The presenters and panelists examined our most entrenched and challenging issues, from reducing our dependence on oil to ensuring that people everywhere have access to a good education, quality health care and well-paying jobs. Interestingly, the conference was peppered with references to and comments on life extension. Life extension was even listed as one of the primary human accomplishments on a short list starting with harnessing fire and inventing the wheel. There was even one reference to “overcoming death”. This was astounding to me, since this was a cutting edge group in many ways, yet very much mainstream at the highest levels of business, journalism, economics, politics, health care and education.

(Oops. Fast forward 13 days. I had a system crash on April 27th, and just got my computer back today. That’s why you haven’t heard from me for a while.)

OK. Here we are, 2 weeks after the conference. Since then, I attended a memorial service of a very close friend. Everyone there was saddened by his death. He was one of the most creative and intelligent people I ever know. And his life came to an abrupt end long before his time. I spent a good part of my time wondering how much the world will unknowingly suffer from missing out on the wisdom he will no longer pass on. Gary was a consummate teacher. Maximum Life Foundation is all about putting an end to these tragic wastes of humanity.

Now back to my original thought before longevity news summaries, this time dealing heavily on cancer.

You cannot believe how encouraged I am to see the longevity meme spread to the upper echelons of business, science, journalism and politics. We don’t look so radical any more. All it will take is one major proof of concept, a killer app, to open the financial floodgates of research and development money. We’re working on some of those now and hope to demonstrate some dramatic things in the near future.