Fight Aging!

FIGHT AGING! NEWSLETTER
June 10th 2013

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!

To subscribe or unsubscribe to the Fight Aging! Newsletter, please visit the newsletter site:
https://www.fightaging.org/newsletter/

CONTENT

• Further Thoughts on Advocacy for Radical Life Extension
• Being Healthy Seems Like a Good Plan
• Considering the Details of Replacing the Brain
• The Incentives Associated With Becoming a Machine Entity
• Latest Headlines from Fight Aging!
  • More on Dmitry Itskov and the 2045 Initiative
  • Skepticism on the Near Future of Rejuvenation Biotechnology
  • Notes from the 2013 AGE Meeting
  • Early Registration Deadline for the 2013 Strategies for Engineered Negligible Senescence (SENS) Conference
  • Reviewing the Aging of Bone
  • Adiponectin and Visceral Fat Tissue in Aging
  • A Man Does Not Grow Old Like a Cart, But Rather Like a Horse
  • Overreacting in the Direction of Doing Nothing
  • Quantifying Neurogenesis in Adult Humans
  • A Good Scientific Polemic on Aging

FURTHER THOUGHTS ON ADVOCACY FOR RADICAL LIFE EXTENSION
https://www.fightaging.org/archives/2013/06/further-thoughts-on-advocacy-for-radical-life-extension.php

Greatly extending the healthy human life span has always been one of the core goals advocated by transhumanist authors. Degenerative aging and the suffering and death that it causes are limits, and the philosophy of transhumanism is to develop the technological means to make limits optional - to create choice where no choice is presently possible. As a species we have greatly changed the human condition to date by improving our surroundings and our tools, but in the future we will change it by improving ourselves. To create medical technologies that enable the choice not to age, suffering, and die is the most important of all goals. The personal relevance of everything else that the future might bring depends upon being alive to see it, after all.

Transhumanist research and development takes place all around us, and the human condition changes a little every year as a result, but research into the means of extending healthy life is very sparsely funded. The public at large seems in the most part indifferent to the prospect of longer lives. Does this mean that we are doing too poor a job in advocacy and fundraising, or that good progress over the past few decades has taken place in the face of a widespread lack of interest and even hostility towards longevity science? It's certainly the case that there is more deliberate funding and advocacy for rejuvenation research today than ten years ago, even though it's still small in comparison to other fields of medical science.

Everyone has an opinion on what we might do differently to persuade more people to support scientific research aimed at the reversal of aging. To follow on from last week's post on advocacy and the lack of funding for rejuvenation research, I thought I'd point out a few thoughts from Maria Konovalenko of the Science of Life Extension Foundation. They are presented beneath this banner:

How can Transhumanism Win?

The topics of horror of death and despair of aging are poorly exposed in tranhumanist rhetoric. In the 14th century, in the plague times, death used to be one of the main topics of visual arts. Nowadays the topic of horror of death struggles its way to the surface only on cigarette packs in a few countries of the world. There is an unspoken ban on documentary demonstration of the moment of human death. Death itself is often embellished, heroized and named necessary for striving of other people.

We claim that there is nothing more dreadful than death, and our main goal is to fight it. We understood that one of the most powerful impact tools are not the rational arguments, but visual images. We are interested in creating the new art that describes the horrors of aging and death with the aim of increasing the motivation of people to fight for radical life extension, for immortality. So, if you happen to know some artists, tell them about tranhumanist ideas and about the urgent need of new art that will help defeat death.

People don't like to talk about death, and in my experience can become very resistant or even hostile when the topic of rejuvenation research, cryonics, or other ways in which we can try to address death are brought up in the course of conversing about death. The death of older public or private figures should be teaching moments for longevity science, but in practice turn out to be a good opportunity to make people angry. This is an interesting response but not very helpful. People rarely want to talk about death in any detail at other times, and when it cannot be avoided as a topic they often react angrily to any thought of avoiding death through science and research.

So I think there's something to be said for giving death a 14th century prominence. Perhaps fewer people will choose to bury their heads in the sand. Konovalenko offers up some other points and opinions as well, which you may or may not agree with but which are all worth at least a little thought. One of these days someone will figure out the key to open the floodgates of support for extended healthy life and rejuvenation research, but that won't happen without a diversity of effort aimed at a better way forward.

BEING HEALTHY SEEMS LIKE A GOOD PLAN
https://www.fightaging.org/archives/2013/06/being-healthy-seems-like-a-good-plan.php

The near future of human longevity will be determined by progress in medical technology. This is the only thing that might result in the option to live in good health for decades or more beyond the span of years enjoyed by your grandparents: there's no other way to extend healthy life to this degree. It's new medicine or nothing, and the critical factor is whether proposed forms of rejuvenation biotechnology such as those described in the SENS proposals are developed rapidly or slowly. At present the pace is slow, but we may yet manage to obtain the funding and attention needed to turn rejuvenation into a field as large and energetic as cancer research or stem cell medicine.

Present day good health practices cannot greatly extend your life, and they cannot even reliably ensure that you reach extreme old age in good shape, or indeed at all. Most exceptionally healthy people don't make it to 90 - but of course the toll is far worse among those who are sedentary, fat, and smoke. The consensus from various studies appears to be that you can give yourself the expectancy of five to ten additional years above the average through regular exercise, and you can drop five to ten years or more below the average through being obese or smoking. Calorie restriction may or may not be as good as exercise for human life expectancy, though it is expected by the research community to extend life. The benefits to short term measures of health are arguably far better than those produced by exercise, but it's hard to find a big enough study population for calorie restriction to produce the same sorts of quality statistic data as are available for exercise.

Taking the 80/20 approach to being healthy isn't just a quality of life and lower medical expense thing nowadays, however. It was in the past, because there was no possibility of radical life extension through medical technology on the horizon. Now, however, rejuvenation biotechnology is within a few decades of implementation, with that countdown starting just as soon as the funding ramps up to appreciable levels. How long will it take to generate the funds and interest? No one knows.

So who will make it to survive into the era of rejuvenation and the defeat of degenerative aging? Certainly most of the people born within the past decade. But those of us presently in the middle of life are looking at a great deal less certainty. For hundreds of millions of people a decade one way or another will be the difference between death and living to be young again, for as long as you care to keep going. Are you one of the people in that zone of uncertainty? Perhaps - but you'll never know until it's too late. That's why the whole healthy lifestyle thing is important: it's one of the only two ways in which you can shift the odds in a favorable direction, with the other being to help accelerate research and development.

With this in mind, here are a few recent research results on the topic of health and lifestyle. They are a reminder that a better lifestyle is a good thing from the point of view of your likely length of life, medical expenditures, and the risk of suffering age-related medical conditions.

Vegetarian Diets Associated With Lower Risk of Death

Vegetarian diets are associated with reduced death rates in a study of more than 70,000 Seventh-day Adventists with more favorable results for men than women. There were 2,570 deaths among the study participants during a mean (average) follow-up time of almost six years. The overall mortality rate was six deaths per 1,000 person years. The adjusted hazard ratio (HR) for all-cause mortality in all vegetarians combined vs. nonvegetarians was 0.88, or 12 percent lower, according to the study results. The study notes that vegetarian groups tended to be older, more highly educated and more likely to be married, to drink less alcohol, to smoke less, to exercise more and to be thinner.

Evidence mounts that 4 lifestyle changes will protect heart, reduce your risk of death

A large, multi-center study led by Johns Hopkins researchers has found a significant link between lifestyle factors and heart health, adding even more evidence in support of regular exercise, eating a Mediterranean-style diet, keeping a normal weight and, most importantly, not smoking. The researchers found that adopting those four lifestyle behaviors protected against coronary heart disease as well as the early buildup of calcium deposits in heart arteries, and reduced the chance of death from all causes by 80 percent over an eight-year period.

Healthy Lifestyle Choices Mean Fewer Memory Complaints

To examine the impact of these lifestyle choices on memory throughout adult life, UCLA researchers and the Gallup organization collaborated on a nationwide poll of more than 18,500 individuals between the ages of 18 and 99. Respondents were surveyed about both their memory and their health behaviors, including whether they smoked, how much they exercised and how healthy their diet was.

"We found that the more healthy lifestyle behaviors were practiced, the less likely one was to complain about memory issues." In particular, the study found that respondents across all age groups who engaged in just one healthy behavior were 21 percent less likely to report memory problems than those who didn't engage in any healthy behaviors. Those with two positive behaviors were 45 percent less likely to report problems, those with three were 75 percent less likely, and those with more than three were 111 percent less likely.

CONSIDERING THE DETAILS OF REPLACING THE BRAIN
https://www.fightaging.org/archives/2013/06/considering-the-details-of-replacing-the-brain.php

Of the billions presently alive, some fraction will go on to live for thousands of years. The age of rejuvenation therapies is just around the corner, and new approaches to medicine will enable the old to be made young again. This will happen within a few decades, perhaps soon enough for those in middle age today in wealthier regions, perhaps not. Whatever the timeline turns out to be - and we have the opportunity to accelerate it - the fundamental forms of cellular and molecular damage that cause aging will become just another set of chronic medical conditions that are kept under control with regular treatments: periodically repaired, so as to maintain youth and indefinitely postpone age related disease.

In this future people will still die, however. The current mortality rate due to fatal accidents, if maintained, would give an ageless, disease-free person a life expectancy of a few thousand years. If you want to live longer than that, then you require either (a) the means of greatly reducing the occurrence and severity of accidents, or (b) to ability to change yourself to be less vulnerable. Those people alive today who are still alive ten thousand years from now, and some will be, will most likely have altered themselves dramatically, abandoning flesh and the human form in favor of far more robust machinery.

It should not be terribly controversial to suggest that a hundred years from now replacing your body with an artificial chassis will be a very feasible, cost-effective option. The manufacturing and design technologies of that era will involve mature artificial intelligence and precise atomic construction. An artificial body should be a simple undertaking by that point, and there's more than enough time to wait for that technology if you survive today's first hurdle of living long enough to benefit from the first wave of rejuvenation biotechnologies.

When it comes to transforming yourself into an entity likely to survive for longer than recorded human history to date, the body is a trivial matter, however, hardly worth putting much thought into at this point. Almost any easily replaceable, mobile, and very robust machinery will do. The more interesting questions relate to the brain and the self: how can you switch out the intricate biology of the brain for more durable machines without killing yourself in the process? All that is you is encoded as data in the fine structure of brain tissue. Making a copy of your mind to run as software seems like a feasible undertaking, something that can be envisaged even today: it's possible to speculate in a useful fashion as to how that might be accomplished within the next few decades. But a copy of you is its own entity, not you, and there are many other questions and doubts relating to the continuity of the self associated with an intelligence running as software.

The best approach to replacing the brain while retaining your self is a slow process of replacing each neuron with machinery that serves exactly the same purpose and integrates with the rest of the brain in exactly the same way as the neuron did. The brain creates and loses neurons on an ongoing basis already - though a plausible replacement methodology would run many times faster than that process, and would replace neurons that are normally never replaced. Some of those cells last a lifetime.

This gradual neural replacement is a fine thing to talk about in abstract, but how would it even work in practice? How would a neuron machine be constructed? How do you assure continuity of the self when doing this for real? Some people have put a fair amount of thought into this topic, even though it is a far future prospect and we still have to sort out the first step of not aging to death in the bodies and brains we have now. Over at the Rational Argumentator you'll find an eleven part series on the important parts of the path to replacing the brain with machinery. There's quite a lot of reading material there, and I make no warranty as to the quality and rigor of the work, but I think you'll find it interesting.

1. The Moral Imperative and Technical Feasibility of Defeating Death
2. Immortality: Material or Ethereal? Nanotech Does Both!
3. Concepts for Functional Replication of Biological Neurons
4. Gradual Neuron Replacement for the Preservation of Subjective-Continuity
5. Wireless Synapses, Artificial Plasticity, and Neuromodulation
6. Mind as Interference with Itself: A New Approach to Immediate Subjective-Continuity
7. Neuronal 'Scanning' and NRU Integration
8. Squishy Machines: Bio-Cybernetic Neuron Hybrids
9. Choosing the Right Scale for Brain Emulation
10. Maintaining the Operational Continuity of Replicated Neurons
11. Immortality: Bio or Techno?

If we seek to replace biological neurons with artificial equivalents, once we have a simulation of a given neuron in a computer outside the body, how is that simulated neuron to communicate with the biological neurons still inside that biological body, and vice versa? My solution was the use of initially MEMS (micro-electro-mechanical systems) but later NEMS (nano-electro-mechanical-systems) to detect biophysical properties via sensors and translate them into computational inputs, and likewise to translate computational output into biophysical properties via electrical actuators and the programmed release of chemical stores (essentially stored quantities of indexed chemicals to be released upon command). While the computational hardware could hypothetically be located outside the body, communicating wirelessly to corresponding in-vivo sensors and actuators, I saw the replacement of neurons with enclosed in-vivo computational hardware in direct operative connection with its corresponding sensors and actuators as preferable.

I didn't realize until 2010 that this approach - the use of NEMS to computationally model the neurons, to integrate (i.e., construct and place) the artificial neurons and translate to biophysical signals into computational signals and vice versa - was already suggested by Kurzweil and conceptually developed more formally by Robert Freitas, and when I did, I felt that I didn't really have much to present that hadn't already been conceived and developed.

However, since then I've come to realize some significant distinctions between my approach and Brain-Emulation, and that besides being an interesting story that helps validate the naturality of Immortalism's premises (that indefinite longevity is a physically realizable state, and thus technologically realizable - and what can be considered the "strong Immortalist" claim: that providing people the choice of indefinite longevity if it were realizable is a moral imperative), I had several novel notions and conceptions which might prove useful to the larger community working and thinking on these topics.

THE INCENTIVES ASSOCIATED WITH BECOMING A MACHINE ENTITY
https://www.fightaging.org/archives/2013/06/the-incentives-associated-with-becoming-a-machine-entity.php

In the near future it will be possible to build artificial bodies, and some decades after that it will become possible to gradually replace the biology of our brains with more durable and capable nanomachinery. A diverse industry of brain-computer interfaces and artificial intelligences will arise and come to maturity along the way. Will we in fact largely become a species of intelligent machines within the next few centuries? By this I mean designed machines, as opposed to the evolved machines we presently are: entities that are human, but very distant from our present forms, functions, and limitations. When you design the machinery, rather than just working with what you have been given, an enormous range of possibilities open up. For one thing, even very complex machines can be designed to be far more robust and easily maintained than our biology, allowing a person-turned-machine-intelligence the option of an extremely long life expectancy.

Will there be a population-scale rush away from biology towards the new and better options for bodies and brains as soon as they become a practical concern? Some people think so, and I believe it is an inevitable transition given the far greater capabilities that could be provided by being more than merely biological. Perhaps not a rush, but a transition over time, leaving behind a disparate collection of Amish-like groups and poor communities that coexist and trade with the transitioned human societies. On the large scale people follow incentives: they buy the new tools that improve life, boost economic output, and add new options at an affordable price. Those groups with the greatest economic output grow to become the cultural mainstream over time. There's no reason to think that any of this will change, no matter whether society is running on silicon or neurons. Here is an interesting thought, though:

Aubrey de Grey on Ending Aging and the Human Future

I spoke with Aubrey briefly on the topic of the future of humanity, and the potential scenarios (often discussed in the world of transhumanism and futurism) that might involve moving our human conscious into other substrates, giving us long-lasting silicon bodies and potentially moving our minds into computers that are more durable and reliable that our current biological grey matter.

It is Aubrey's belief that the desire to leave our biological substrate will diminish as the "down-sides" of remaining purely biological go down. In other words, when we can more-or-less live forever in our present bodies, Aubrey believes that we will likely not wish to remove ourselves from them. The negative aspects of "being made of meat" - as he aptly put it - would be mitigated by an absence of disease and an absence of the recurring damage which is the origin of aging itself.

Another way of looking at the incentives of moving from biology to machinery is that it is not just a matter of chasing something better, but also a matter of leaving something undesirable. Discomfort is a great motivator, and evading the terrible suffering and death caused by aging is important to many of those who look with hope to a transhumanist future. Given an industry of rejuvenation medicine and complete control over aging, disease, and pain, however, being a standard issue biological human begins to look like an indefinitely comfortable existence - barring rare fatal accidents, of course, but who goes through life thinking that will happen to them?

So the argument here is that medicine, and specifically the defeat of degenerative aging, will alter the incentive landscape in a way that leads more people to choose to remain biological, even when it is possible to become a machine intelligence with greater capabilities and durability. My estimate of the timelines is that rejuvenation will be a going concern a long way prior to the point at which slow, safe replacement of the brain's neurons with nanomachinery is possible. It's possible that the increased comfort provided by the removal of age-related suffering and death will slow down progress towards ways to move biology to machinery.

But we shall see. It is interesting to think about these things, but important not to lose sight of the fact that researchers still need to build the means to reverse degenerative aging. There are detailed plans to show what needs to be done in order to rejuvenate the old, there are plenty of researchers ready to jump in and perform the work if given funding, but resources and public interest are - as ever - lacking. The future only stays fascinating if you remain alive to see it, so consider helping to speed progress towards the means of human life extension.

LATEST HEADLINES FROM FIGHT AGING!

MORE ON DMITRY ITSKOV AND THE 2045 INITIATIVE
Monday, June 3, 2013
https://www.fightaging.org/archives/2013/06/more-on-dmitry-itskov-and-the-2045-initiative.php

The forthcoming Global Futures 2045 conference is attracting media attention to Dmitry Itskov's 2045 Initiative. The technological aim of the program is to move out of our biology and into durable, ageless machine bodies and minds as quickly as possible - though of course an upload of you is not you, but rather a distinct copy. That will not prevent people from choosing to create uploaded copies of themselves when the option becomes available, and will not diminish the enthusiasm of those who belief that a copy of you is you. Moving from a biological mind to a machine mind without copying or destroying yourself would have to be a much more gradual process, perhaps by a slow replacement of individual neurons and synapses with more resilient nanomachines that serve the same purpose.

The technologies needed to enable these goals are distant but not implausible - there is a lot of work between here and there. To my eyes this all seems like a harder and slower track to agelessness than the biological path of rejuvenation biotechnology as championed by the SENS Research Foundation. We don't have all the time in the world to wait for the future until researchers can repair the various known underlying causes of aging, and sorting that out in the biology we have today seems more viable than building a new home for the mind.

It is hard to imagine a day when the ideas championed by Mr. Itskov, 32, a Russian multimillionaire and former online media magnate, will not seem strange, or at least far-fetched and unfeasible. His project, called the 2045 Initiative, for the year he hopes it is completed, envisions the mass production of lifelike, low-cost avatars that can be uploaded with the contents of a human brain, complete with all the particulars of consciousness and personality. [He] has the attention, and in some cases the avid support, of august figures at Harvard, M.I.T. and Berkeley and leaders in fields like molecular genetics, neuroprosthetics and other realms that you've probably never heard of.

Mr. Itskov's role in the 2045 Initiative is bit like that of a producer in the Hollywood sense of the word: the guy who helps underwrite the production, shapes the script and oversees publicity. He says he will have spent roughly $3 million of his own money by the time the [forthcoming Global Futures 2045 conference] is over, and though he is reluctant to disclose his net worth - aside from scoffing at the often-published notion that he's a billionaire - he is ready to spend much more.

For now, he is buying a lot of plane tickets. He flies around the globe introducing himself to scientists, introducing scientists to one another and prepping the public for what he regards as the inevitable age of avatars. In the span of two weeks, his schedule took him from New York (for an interview), to India (to enlist the support of a renowned yogi), home to Moscow, then to Berkeley, Calif. (to meet with scientists), back to Moscow and then to Shanghai (to meet with a potential investor).

Mr. Itskov says he will invest at least part of his fortune in such ventures, but his primary goal with 2045 is not to become richer. In fact, the more you know about Mr. Itskov, the less he seems like a businessman and the more he seems like the world's most ambitious utopian. "We need to show that we're actually here to save lives. To help the disabled, to cure diseases, to create technology that will allow us in the future to answer some existential questions. Like what is the brain, what is life, what is consciousness and, finally, what is the universe?"

I might not believe that Itskov's vision is the best way forward towards greater longevity, but I do think that we would all benefit from the existence of a good many more ambitious utopians of this sort.

SKEPTICISM ON THE NEAR FUTURE OF REJUVENATION BIOTECHNOLOGY
Monday, June 3, 2013
https://www.fightaging.org/archives/2013/06/skepticism-on-the-near-future-of-rejuvenation-biotechnology.php

Many in the mainstream research community still believe that the only viable way forward to extend life is to slow aging by manipulating metabolism - such as by trying to replicate the effects of calorie restriction through drugs. In their view, this is a long, hard, slow project that is unlikely to produce meaningful results within our lifetimes, and when it does produce results they will only induce a modest extension of healthy life.

These researchers do not yet acknowledge the potential of repair-based strategies that aim to reverse the forms of age-related cellular damage that most likely cause aging - the known fundamental differences between old tissue and young tissue - and thus produce rejuvenation. This should be less expensive and faster in addition to producing a better end result, such as indefinite extension of healthy life.

Extending life by slowing aging has been accomplished in many different species and in many different ways, but rejuvenation research is a younger, underfunded field that has yet to advance to the point at which it can boast the same panoply of demonstrations. All we have so far are examples of rejuvenation achieved in some aspects or mechanisms of some tissues, and not so many of those either. Even in the scientific community, people tend to believe in what they can see rather than what is plausible but not yet in evidence:

In an age of breakneck technological and scientific progress, it can seem at times like anything's possible. [For] all the exponential advances, though, some technologies remain firmly in the realm of science fiction. We can't engineer genius babies. We're never getting our hoverboards. And, perhaps most dispiritingly of all, we haven't figured out a way to cheat death.

It isn't for lack of trying. Research centers around the world have teams devoted to the study of human longevity, and scientists have been working furiously for years to uncover the secrets of long life in everything from mice to yeast to hydra. In fact, they're making a lot of progress, and there's good reason to be optimistic that they'll someday hit on a breakthrough that will allow people to live significantly longer than they do today. But if you're sitting around waiting for the singularity, you might want to stand up and go for a jog instead.

One problem is that humans are a lot harder to study than mice. A [study] found that mice injected with a substance that inhibited a molecule known as NF-KB lived longer than normal. Mice injected with NF-KB itself died young. That seems like compelling evidence that the molecule, which is involved in the body's response to stress, plays a role in how mice age. But what works in mice doesn't necessarily work in humans. And who's going to approve the study that injects people with an NF-KB inhibitor and to see how soon they die?

No one - especially since the FDA doesn't recognize aging as a disease. That makes regulations and approvals trickier for potential anti-aging treatments. And some researchers in the field complain that it makes it harder to get funding for big studies. The bigger-picture problem is that human longevity is a confluence of so many factors - genes, nutrition, lifestyle, luck - interacting in so many complex ways that there is unlikely ever to be a surefire way to live to 120.

NOTES FROM THE 2013 AGE MEETING
Tuesday, June 4, 2013
https://www.fightaging.org/archives/2013/06/notes-from-the-2013-age-meeting.php

The American Aging Association (AGE) held its 2013 meeting a few days ago. The program was a mix of old-school and irrelevant research such as the effects of specific foods on parameters of aging, nothing that's going to help us meaningfully extend life there, and the new and interesting such modulating autophagy to slow the effects of aging in specific tissues. Here are some notes from an attendee:

Several talks involved growth hormone one way or another. Growth hormone is hyped as an anti-aging remedy by many supplement sources, but its benefits are likely to be short-term, and there is substantial risk that it actually increases mortality risk in the long run. Holly Brown-Borg made this point quite explicitly. Her research is centered on two strains of mice, a dwarf strain which has a genetic defect for growth hormone, and lives 50% longer, the other is genetically engineered to have extra growth hormone, and it lives 50% shorter than ordinary lab mice. The dwarf mice are super-healthy and don't get cancer, but you can make them sick by giving them growth hormone.

There were several major presentations at the conference focused on rapamycin. Rapamycin binds to two sites, called TORC1 and TORC2 (TOR stands for "target of rapamycin"). Joe Bauer reported his theory that TORC2 holds most of the benefits, and TORC1 most of the dangers of rapamycin, and he is working to separate the two effects. Arlan Richardson offered an hour-long advertisement for rapamycin as a cancer treatment, for cardiac health and prevention of cognitive decline. He reluctantly admitted that it also causes cataracts, slows healing, and contributes to Type 2 diabetes. Conference consensus (including this author) is that rapamycin is an exciting new vehicle for studying aging, but as a general tonic, it's not ready for prime time.

I've been attending these meetings for several years, and I continue to find that the meetings are small, there are almost no MDs, and the research seems to occupy a backwater between bench science and medical research. Compared to cancer research or heart or lung disease, the field is way underfunded. Still, research in anti-aging medicine is growing, as policy-makers realize it is a way to address many diseases of old age with a powerful new paradigm.

EARLY REGISTRATION DEADLINE FOR THE 2013 STRATEGIES FOR ENGINEERED NEGLIGIBLE SENESCENCE (SENS) CONFERENCE
Tuesday, June 4, 2013
https://www.fightaging.org/archives/2013/06/early-registration-deadline-for-the-2013-strategies-for-engineered-negligible-senescence-sens-conference.php

A reminder from the SENS Research Foundation staff that the early registration and abstract submission deadlines for this year's SENS6 conference are coming up on June 15th:

You are cordially invited to participate in the sixth Strategies for Engineered Negligible Senescence (SENS) Conference, which will be held from 3rd - 7th September, 2013 at Queens' College, Cambridge. June 15th is the deadline for discounted registration and abstract submission. After this deadline, all registration fees rise by £150.00. Also, after that date, we cannot guarantee that submitted abstracts will be considered for oral presentation or that they will be included in the conference abstract book.

All details of the conference, including forms for abstract submission and online registration, are at the conference website. The conference program features 47 confirmed speakers so far, all of them world leaders in their field. As with previous conferences hosted by SENS Research Foundation, the emphasis of this meeting is on the design and implementation of rejuvenation biotechnologies - applications of regenerative medicine to age-related disease. Such biomedical interventions may jointly constitute a comprehensive panel of therapies that is sufficient to prevent or cure the diseases of aging, ensuring robust health for all.

REVIEWING THE AGING OF BONE
Wednesday, June 5, 2013
https://www.fightaging.org/archives/2013/06/reviewing-the-aging-of-bone.php

Aging causes bone to deteriorate, as is the case for all types of tissue in our bodies. This open access paper reviews what is known of the higher level mechanisms involved in bone aging, but it remains the case that little work is done to link these mechanisms with specific forms of age-related damage, such as those outlined in the SENS research and development proposals. Most researchers work towards linking specific outcomes in aging to the secondary results of damage, such as changes in gene expression and rising levels of oxidative stress:

With advancing age, the amount of bone resorbed by the osteoclasts is not fully restored with bone deposited by the osteoblasts and this imbalance leads to bone loss. Thus, aging and osteoporosis are intimately linked.

Similar to other tissues, oxidative stress increases in bone with age. This article reviews current knowledge on the effects of the aging process on bone and its cellular constituents, with particular emphasis on the role of reactive oxygen species (ROS). FoxOs, sirtuins and the p53/p66shc signaling cascade alter osteoblast number and bone formation via ROS-dependent and -independent mechanisms.

Specifically, activation of the p53/p66shc signaling increases osteoblast/osteocyte apoptosis in the aged skeleton and decreases bone mass. FoxO activation in osteoblasts prevents oxidative stress to preserve skeletal homeostasis. However, while defending against stress FoxOs bind to β-catenin and attenuate Wnt/T-cell cell factor transcriptional activity and osteoblast generation. Thus, pathways that impact longevity and several diseases of ageing might also contribute to age-related osteoporosis.

ADIPONECTIN AND VISCERAL FAT TISSUE IN AGING
Wednesday, June 5, 2013
https://www.fightaging.org/archives/2013/06/adiponectin-and-visceral-fat-tissue-in-aging.php

Adiponectin is one of many signaling proteins generated by fat cells and has been showing up of late in research aimed at better understanding the ways in which the operation of metabolism determines the pace of aging. Visceral fat tissue is very active in terms of determining the operating state of your metabolism as a whole. Carrying more visceral fat is associated with worse long-term health and a shorter life expectancy, thought to be achieved through mechanisms such as raised levels of chronic inflammation. Studies in mice show that removing visceral fat extends life. Altered levels of adiponectin and related proteins may be one of the ways in which excess fat (adipose tissue) sabotages your health, but given the evidence from studies of the metabolism of long-lived individuals it's probably not a simple relationship:

Adipose tissue is an active metabolic organ secreting adipocytokines which are involved in the energy homeostasis and regulation of glucose and lipid metabolism. Aging is associated with fat redistribution, which is characterized by loss of peripheral subcutaneous fat and accumulation of visceral fat. Visceral adipose tissue is more involved in the development of metabolic diseases than subcutaneous adipose tissue.

Aging also alters the function, proliferation, size, and number of adipose cells which leads to alterations in the secretion, synthesis and function of the adipocytokines. Adiponectin is an insulin sensitizing, anti-inflammatory, and antiathoregenic adipokine. Centenarians have higher adiponectin levels associated with longevity. However, in older individuals ‑ age 65 or more ‑ adiponectin is associated with higher mortality. Dysregulation of adiponectin in older individuals may be due to loss of function of circulating adiponectin or a response to increased inflammatory process. Longitudinal increase in adiponectin levels with aging rather than genetically high adiponectin levels may translate to increased mortality in older patients.

The adipocytokine leptin is traditionally viewed as a product of adipocytes that can exert endocrine effects. There have been conflicting reports of not only the effects of aging on leptin, but also the effects of leptin on age-related diseases including sarcopenia, Alzheimer's disease and cardiovascular diseases. Aging is also associated with resistance to leptin and/or to a decrease of receptors for this hormone.

A MAN DOES NOT GROW OLD LIKE A CART, BUT RATHER LIKE A HORSE
Thursday, June 6, 2013
https://www.fightaging.org/archives/2013/06/a-man-does-not-grow-old-like-a-cart-but-rather-like-a-horse.php

Here is an interview in Russian with with researcher Alexei Moskaliev, associated with the Science for Life Extension Foundation. The Russian gerontology community's view of aging has a somewhat different slant from that of the English language world - there is more of a tendency towards the programmed aging viewpoint, for one thing, in which aging is thought to be a genetic program that leads to damage rather than damage that causes epigenetic changes in response.

Automated translation of Russian remains terrible, I should note, so be prepared to have to interpret the output where it becomes confusing:

Stress leads to substantial deviations of the external and internal parameters of the optimum life span of cells (concentration of nutrients, pH, oxygen level and temperature). Oxidative stress, genotoxic stress, mitochondrial stress, endoplasmic reticulum stress - different kinds of complex intracellular processes leading to the accumulation of damaged cellular structures. Damaged cells cope worse with the problems, and are not able to participate in physiological functions and tissue regeneration.

Gerontologists often talk about the fundamental difference between aging "carts" and aging "horses." The cart accumulates damage and ceases to perform its function. The horse is actively opposing internal failure at the level of each cell for as long as these arrangements do not themselves fail, and this is called stress tolerance. Mechanisms involving DNA damage response proteins, membrane lipids, and detoxification of toxins work with reduced effectiveness with advancing age. Therefore, the real cause of aging is not actually the accumulation of cell damage but rather the loss of mechanisms to combat injuries.

Many diseases are characterized by an exponential growth with increasing age, indicating that their direct connection with aging. This suggests that aging is the cause of most of these diseases (many types of cancer, cardiovascular disease, retinopathy, cataracts, type II diabetes, etc.) and an important risk factor for other causes of death (viral diseases, accidents, etc.). Some authors believe that it's time to talk about aging as a disease, and age-related pathologies are its manifestations or biomarkers. The adoption of this approach would change modern medicine.

In struggling with specific manifestations (individual age-related pathologies) doctors reach only short-term success. By suppressing the causes of aging, including age-related decline in the activity of stress-resistance genes we may expect much more progress in both prolonging life and improving quality of life.

OVERREACTING IN THE DIRECTION OF DOING NOTHING
Thursday, June 6, 2013
https://www.fightaging.org/archives/2013/06/overreacting-in-the-direction-of-doing-nothing.php

I believe it's a grand waste of time to try to optimize your health through presently available methods. It's very easy to get the 80/20 best expected outcome: exercise regularly, practice calorie restriction with optimal nutrition, and refrain from methods of self-harm such as smoking, jumping off tall buildings, and so on. This is not rocket science.

There is no scientific support for going beyond this to tinker with types of exercise, esoteric supplements, and the like, however. There's no way to link your future life expectancy with your activities, and there is no good weight of evidence to suggest that any of the thousands of available options are better or worse for life expectancy than the 80/20 approach. There is always someone out there pushing a new fad, but that doesn't make it right, useful, or legitimate. Maybe you'll improve your life span by a few percentage points, and maybe you won't. There is no way to tell, and the time and money easily wasted on that endeavor is better put to other uses that are far more likely to extend your healthy life span - such as supporting the research needed to produce rejuvenation biotechnology.

That all said, it's possible to go too far in the direction of doing little but the basics for your health - if you are thinking of letting it all go and doing nothing for your health, that will have consequences. This view is illustrated in the post quoted below, wherein the author rejects calorie restriction on the basis that the present consensus view is that it won't extend healthy life in humans by all that much. This ignores the amazing health benefits demonstrated in human studies to date - calorie restriction may or may not extend human life by more than a few years, but it certainly greatly improves measures of health and lowers risk of age-related disease. It seems silly to reject something shown to produce larger benefits for basically healthy people than can be gained by any presently available medical technology.

I want to live longer and help others do the same. I assumed the most effective way to do that is by understanding the science of aging and then engineering solutions to extend human lifespan. That is why I became a biomedical researcher and over the past several years I have pursued this goal almost single-mindedly.

When a 2004 study showed that reducing the calorie intake in mice extended their life by 42%, I enthusiastically embraced the results and even put myself on a calorie restricted diet. But, subsequently, a 2012 study showed that long-term calorie restriction may not have the promised benefits. On the contrary, fewer calories without the required nutrients might actually cause harm.

Calorie restriction is not the first such "promising" route that eventually did not live up to the promise, and it will not be the last. Antioxidants showed promise in holding back diseases caused by aging, but now we know that antioxidant supplements are more likely to shorten your life.

Earlier in May, researchers showed that reducing a protein called NF-kB in mouse brains modestly improved their lifespan. I am not holding out for this result either. Before too long, I'm sure there will be reports of severe side effects of manipulating levels of NF-kB.

Looking at the data I have come to the conclusion that "doing nothing" may be the best option in most cases. This may not be as pessimistic as it sounds and it is definitely not to say that research in fighting aging must not be carried out. When I say "do nothing", I am assuming that you do not smoke or drink too much alcohol, and have access to medical care in case of injury. Such measures are bound to increase your lifespan.

But currently, not intervening in the aging process is more likely to help you live longer than trying any of the methods I've mentioned, not by a few months but by many years. Trying any of those interventions may actually cause harm, and will do so for the foreseeable future.

I agree with the basic thesis here, which is to be a late adopter and refrain from chasing the latest fads and data - this is an aspect of what I am arguing with my view on the futility of trying to optimize health past the 80/20 basics. But again, you can take it too far and throw the baby out with the bath water. Calorie restriction with optimal nutrition has an enormous weight of evidence gathered over decades backing its benefits and safety, and the same goes for regular exercise.

QUANTIFYING NEUROGENESIS IN ADULT HUMANS
Friday, June 7, 2013
https://www.fightaging.org/archives/2013/06/quantifying-neurogenesis-in-adult-humans.php

It was once thought that the brain did not generate new neurons in adult life, but the evidence for ongoing neurogenesis was found a few decades ago. Levels of neurogenesis in humans have been hard to pin down, but knowing the degree to which it happens naturally has some relevance to attempts to induce a higher rate of neuron creation with the aim of reversing age-related loss of cognitive function. Here researchers find a way to quantify the level of cell turnover in at least one part of the brain:

The birth of new neurons in the adult brain sharpens memory in rodents, but whether the same holds true for humans has long been debated. A [study] reveals that a significant number of new neurons in the hippocampus - a brain region crucial for memory and learning - are generated in adult humans. The researchers used a unique strategy based on the amount of carbon-14 found in humans as a result of above-ground nuclear testing more than half a century ago. The findings suggest that new neurons are born daily in the human hippocampus, offering the tantalizing possibility that they may support cognitive functions in adulthood.

Due to technical limitations, until now it was not possible to quantify the amount of neurogenesis in humans. To overcome this hurdle, [researchers] developed an innovative method for dating the birth of neurons. This strategy takes advantage of the elevated atmospheric levels of carbon-14, a nonradioactive form of carbon, caused by above-ground nuclear bomb testing more than 50 years ago. Since the 1963 nuclear test ban treaty, atmospheric levels of "heavy" carbon-14 have declined at a known rate. When we eat plants or animal products, we absorb both normal and heavy carbon at the atmospheric ratios present at that time, and the exact atmospheric concentration at any point in time is stamped into DNA every time a new neuron is born. Thus, neurons can be "carbon dated" in a similar way to that used by archaeologists.

By measuring the carbon-14 concentration in DNA from hippocampal neurons of deceased humans, the researchers found that more than one-third of these cells are regularly renewed throughout life. About 1,400 new neurons are added each day during adulthood, and this rate declines only modestly with age.

A GOOD SCIENTIFIC POLEMIC ON AGING
Friday, June 7, 2013
https://www.fightaging.org/archives/2013/06/a-good-scientific-polemic-on-aging.php

It is good that scientists are now more willing than in past years to talk about human longevity and the prospects for reversing aging through medical science. That change in attitudes is a necessary part of creating an environment in which rejuvenation research programs like SENS can thrive.

This particular group of researchers holds a different view as to which of the known changes in old cells and tissues are fundamental and thus cause aging: in the SENS outline telomere shortening is a secondary effect and nuclear DNA damage is only a cause of cancer rather than aging, but this paper puts them front and center as primary causes of aging. These researchers are also as yet unwilling to explicitly talk about rejuvenation rather than simply slowing aging, but a rising tide floats all boats.

All in all I'm very pleased to see scientists independently following the SENS model by producing a work that combines (a) specific descriptions of the changes proposed to cause aging and (b) specific proposals on how to use this information to build therapies that will address aging. The paper is open access for the moment at least, so you might take a look:

For some species, living twice as long in good health depends on no more than a few genes. When this fact was revealed by studies on worms three decades ago, it ushered in a golden age of ageing studies that has delivered numerous results, but also sown some confusion. [Researchers are now] publishing an exhaustive review of the subject that aims to set things straight and "serve as a framework for future studies." All the molecular indicators of ageing in mammals - the nine signatures that mark the advance of time - are set out in its pages. And the authors also indicate which can be acted upon in order to prolong life, while debunking a few myths like the belief that antioxidants can delay aging.

The authors are Spanish scientists Maria Blasco (Spanish National Cancer Research Centre, CNIO), Carlos López-Otín (University of Oviedo), and Manuel Serrano (CNIO), along with Linda Partridge (Max Planck Institute for Biology of Ageing) and Guido Kroemer (Paris Descartes University). Their inspiration came from a classic 2000 paper, The Hallmarks of Cancer, [which] marked a watershed in cancer research.

[This] removes the "frivolity" with which aging research is often approached: "It's not about not having wrinkles or living to be a hundred at any cost, but about prolonging disease-free life." [The] scientists are explicit about their final goal, which is "to identify pharmaceutical targets to improve human health during aging."

Another milestone of the paper is that it not only defines the nine molecular hallmarks of aging but orders them into primary hallmarks - the triggers; those that make up the organism's response to these triggers; and the functional defects resulting. This hierarchy is important, because different effects can be achieved by acting on one or other of these processes. By acting on just one mechanism, if it numbers among the primaries, we can delay the aging of many organs and tissues.

There are four primary causes of aging: genomic instability; the shortening of telomeres; epigenetic alterations; and loss of proteostasis.

Genomic instability refers to the defects the genes accumulate over time, due to intrinsic or extrinsic causes. The shortening of telomeres - the protective caps over the ends of chromosomes - is one such defect, but so important a one that it stands as a hallmark in its own right. Epigenetic alterations are the result of lived experience - our exposure to the environment.

Loss of proteostasis has to do with the non-elimination of defective proteins, whose accumulation promotes age-related diseases. With Alzheimer's, for instance, neurons die because plaques form of a protein that should have been eliminated.

The organism responds to these triggers with mechanisms that try to correct the damage, but which can themselves turn deleterious if they become exacerbated or chronic. This is the case of cellular senescence: the cell is induced to stop dividing, and thus prevent cancer, when too many defects are built up, but if the effect is overdone, the tissues - and the body - age.

One therapeutic strategy tested successfully in mice is to stop the telomeres from shortening. "The process can be halted and even reversed in mice," remarks Blasco, an expert in the area, who is convinced that, by and large, "we still have ample room for manoeuver to combat aging and enjoy more years of both life and health."

For López-Otín, "We have diverse opportunities to extend longevity in the not too distant future. Treatments aimed at reducing or correcting the genomic damage that occurs with time are still a distant prospect, but those focusing on metabolic regulation systems may be much more achievable. We don't aspire to immortality, just to the possibility of making life a little better for us all."