Fight Aging! Newsletter, November 18th 2013

November 18th 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!

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  • Help the SENS Research Foundation Raise $100,000 By Year End
  • Biomedical Progress and Economic Growth
  • Exercise Reduces the Cognitive Consequences of Aging
  • An Example of How Not to Organize Your Own Cryopreservation
  • Linking Autophagy to Insulin Signaling in Longevity
  • Latest Headlines from Fight Aging!
    • An Interesting Approach to Accelerate Healing
    • Pessimism: Longevity as a Crisis
    • Arguing That Calorie Restriction Extends Life Via Mitohormesis
    • Slower Brain Aging in Children of Long-Lived Parents
    • Mimicking Glucose Restriction in Nematode Worms
    • Restoring Proteasome Housekeeping Functions in Old Cells
    • Clotting Protein May Play a Role in Hardening of Heart Tissue
    • Considering Priorities in Funding for Rejuvenation Research
    • Being Overweight Increases Risk of Heart Disease Regardless of Metabolic Syndrome
    • Neurotechnology and the 2045 Initiative


The SENS Research Foundation is presently the leading scientific and advocacy organization when it comes to rejuvenation research. Foundation staff coordinate, fund, and carry out the most promising fundamental research into ways to repair cellular and molecular damage that causes degenerative aging. Success in this line of research will result in therapies that can reverse the course of aging, restoring vigor and health to old, frail people, and preventing everyone else from ever becoming old and frail.

The Foundation has grown to a $4 million yearly budget since its creation, these funds provided by philanthropic and grassroots donors. Most of this is used to fund research projects that will advance the state of the art in areas vital to human rejuvenation that are neglected by the mainstream research community. To continue to advance this aim, the Foundation leadership is setting an ambitious community fundraising goal for the remainder of the year, as outlined in an email that arrived today:

Help Us Meet Our Year-End Goal

On behalf of SENS Research Foundation, we would like to thank you for your support throughout 2013. Thanks to your generous donations of time, money, and encouragement, we have been able to continue advancing our work to cure - not just treat, but cure - the diseases of aging. We are accomplishing this goal by funding promising new research, building a strong, collaborative community, and training the next generation of bright, young scientists. No doubt the best example of all of these aspects of our mission in 2013 was our biennial SENS Conference held at the University of Cambridge in September.

The SENS6: Reimagine Aging Conference attracted a record number of leading scientists, clinicians, students, and other supporters. All were amazed at the progress made since SENS5 and were confident that the current work and newly fostered collaborations of the SRF community would lead to more crucial advances in tackling the debilitating diseases of aging. However, in order to continue to increase our impact on advancing the field of regenerative medicine, we need your help. Simply put, more funding will mean more researchers and more labs making cures for the diseases of aging a reality.

Your support will enable us to:

  • Accelerate and add new research projects by expanding the SRF Research Center

  • Make the collaborative effects of the SENS Conference annual rather than biennial

  • Expand our internship program and add a national student symposium
  • We've set an end-of-year funding challenge to raise at least $100,000 between today and December 31, 2013. If you've been thinking about contributing, this is a great time to show your support. Please consider making your tax deductible donation to us today at

    If you are interested in setting up a matching grant please contact us.

    Thank you,

    Mike Kope, CEO
    Aubrey de Grey, CSO
    Tanya Jones, COO

    Some of the items added to the SENS Research Foundation website in the past months were also featured, illustrating the work of the Foundation scientists and allied researchers over the past year. It is well worth looking through to see the tangible results that emerge from directly funding targeted research.

    New SENS6 Highlights Video

    Please take a few minutes to enjoy our latest video featuring highlights of the SENS6 Conference. We hope that you will enjoy the opportunity to experience the sights and sounds of this amazing event. SENS6 brought together leading research scientists and other visionaries in the field of regenerative medicine from around the world.

    The Science Behind SENS

    Curious about what SRF's work actually entails? Interested in the technical details of cutting-edge rejuvenation biotechnology research? If so, you'll definitely want to visit our Research Blog. This section of our website features project updates, descriptions of the concrete actions we are taking to eradicate age-related disease, and in-depth discussions of significant biogerontology topics from our CSO team.

    Check back often for more news about what we're up to in the laboratory, and be sure to take a look at our downloadable Research Report (PDF) if you haven't already.

  • New and Better Clinical Trials for Rejuvenation Biotechnologies - July 31, 2013

  • 2013 Research Report (part 1 of 12): Lysosomal Aggregates - September 01, 2013

  • Unbinding the Mummies: Human Testing of Rejuvenation Biotechnology Targeting α-Synuclein Begins - October 02, 2013

  • 2013 Research Report (part 2 of 12): Mitochondrial Mutations - October 09, 2013

  • 2013 Research Report (part 3 of 12): Cancerous Cells - October 18, 2013

  • 2013 Research Report (part 4 of 12): Extracellular Matrix Stiffening - November 01, 2013

  • 2013 Research Report (Part 5 of 12): Lysosomal Aggregates - November 8, 2013
  • Staff at the SRF Research Center

    Summer Internship Applications: Coming In January 2014. Each year the SENS Research Foundation Summer Internship Program supports training the best undergraduate researchers at leading research institutions around the world. Applications will be available on the SRF website starting January 2014. Mark your calendars, so you can be the first to apply for these amazing research opportunities.

    You can learn more about the internship program and the research projects of past interns in our video spotlights and Education Blog posts.

    SRF's Mitochondrial Mutations Project Awarded LongeCity Grant

    The Mitochondrial Mutations project team, led by Senior Research Scientist Dr. Matthew O'Connor at our Mountain View Research Center, was awarded a LongeCity Research Grant last month. LongeCity is an international non-profit organization that, among other things, supports small-scale science initiatives "to conquer the blight of involuntary death." In two short months, seventy supporters donated over $7,500 which was matched with a $14,000 grant from LongeCity to fund SRF's work to rescue mutated mitochondrial DNA.

    To help fund this and other research projects, please visit As a 501(c)(3) public charity, SENS Research Foundation relies on your support to continue our mission to change the way the world researches and treats age-related disease.


    Researcher Alex Zhavoronkov of the Biogerontology Research Foundation has been somewhat focused on the economic side of aging research in recent years. You might look over his work on the International Aging Research Portfolio, that tracks worldwide funding in this field, and his recently published book, entitled "The Ageless Generation: How Advances in Biomedicine Will Transform the Global Economy", to pick two examples.

    Zhavoronkov sent me a note today to point out a new paper in which he and his co-author take a look at relationships between biomedical research and development and economic growth. I should note that a part of the context in which this paper exists is that this is an age of political angst over the intersection of spending, entitlements, pensions, and growing longevity, characterized by the growing sense that politicians and bureaucrats have engineered a catastrophe from what should be the unmitigated benefit of longer healthy lives. Much has been sold down the river for short term gains claimed by a few. Thus there are many in the community who feel that presenting human rejuvenation as a potential solution to a future of centralized, ever-more-costly healthcare will go some way towards attracting the greater attention and funding that is needed for faster progress towards defeating the diseases and degeneration of aging.

    For my money, I think that fiscal disaster on a national scale is a political problem with political solutions - you can't solve the fall of a government through overspending with biotechnology. Those at the top will just find other ways to waste and steal. However, the examination of links between aging, longevity, advancing biotechnology, and economic growth is valid and useful in and of itself. It is an interesting field, says much about what the sort of work we should be funding, and doesn't receive the level of attention that it should. Zhavoronkov had this to say:

    I think that this is possibly the most important paper I have published so far. We are showing that the economy will grow if governments focus on supporting long-term basic science projects like SENS that are focused on increasing productive longevity and re-focusing the healthcare spending on extending productive life.

    The paper is open access, albeit in PDF format only, so take a look:

    Biomedical Progress Rates as New Parameters for Models of Economic Growth in Developed Countries

    While the doubling of life expectancy in developed countries during the 20th century can be attributed mostly to decreases in child mortality, the trillions of dollars spent on biomedical research by governments, foundations and corporations over the past sixty years are also yielding longevity dividends in both working and retired population. Biomedical progress will likely increase the healthy productive lifespan and the number of years of government support in the old age.

    In this paper we introduce several new parameters that can be applied to established models of economic growth: the biomedical progress rate, the rate of clinical adoption and the rate of change in retirement age. The biomedical progress rate is comprised of the rejuvenation rate (extending the productive lifespan) and the non-rejuvenating rate (extending the lifespan beyond the age at which the net contribution to the economy becomes negative).

    We propose a model that takes into account progress in the biomedical sciences, which in turn affects the size, growth and productivity of the population. In the model, the rate of biomedical progress is the sum of the rejuvenation rate, the rate at which the functions required to perform useful work that were lost to aging or disease are restored, and non-rejuvenating rate, which increases lifespan, but does not restore lost functions.

    We hypothesize that, over the past two decades, economic growth in the developed countries has been partially defined by the ratio of the rejuvenation rate to the overall biomedical progress rate and the retirement age. The biomedical progress rate extends the lifespan and decreases the mortality rates of the population, while the rejuvenation rate allows for the increased productivity of older workers and increases in the retirement age.

    We propose that the increase in the ratio of the rejuvenation rate to the overall biomedical progress rate will result in economic growth. This hypothesis is supported by recent studies showing that the acceleration of aging research focused on increasing longevity and postponing age-related diseases and not the treatment of age-related diseases. Another source of economic growth may come from accelerating the rate of clinical adoption by reducing the time it takes for a biomedical discovery to reach the patient.

    The effects of population aging on economic growth remains a controversial topic in macroeconomics with conflicting schools of thought. While there are many models and simulations that account for population aging, the new parameters introduced in this paper may help enrich the models demonstrating both positive and negative effects of aging on the economy and help model scenarios that go beyond extending historic trends in longevity.


    A fair number of new research results have appeared in the past few weeks relating to ways to modestly reduce the pace of cognitive aging. As we age the mind declines due to a range of failures in the physical structure of the brain that arise from the SENS catalog of low-level cellular and molecular damage of aging. One of the more important ways in which the physical structure of the brain is impacted is via failing cardiovascular health, meaning both a degeneration of the overall process of effectively driving blood through the brain and also a progressive failure of blood vessels, involving loss of tissue elasticity and structural integrity. You might read up on vascular dementia to see how the late stages of this process go, but it is worth remembering that significant damage and failing function exists in the brain's network of blood vessels long before it rises to the level of diagnosis as a named disease or catastrophic structural failure such as a stroke.

    Aging is a progressive, accelerating decline that starts with small consequences and minor losses of function, easily ignored. But these small degenerations will also be repaired in a future of rejuvenation therapies: no-one will wait for decades before undergoing periodic treatments to repair the harms that accumulate in our biochemistry. The next big goal for medical science, something to work towards over the next half century, is an assurance of perfect health for everyone, continuing for as long as desired.

    We are still a way away from that point, however, and so the researchers of today continue to point out that exercise remains one of the most effective means available to slow the onset of degenerative aging. That we live in an age of biotechnology and progress and that exercise is still head and shoulders above most medical technologies should really be taken as a challenge. We can do better, and we should do better, and we must do better if we want to live longer in good health.

    Study finds aerobic exercise improves memory, brain function and physical fitness

    For the study, sedentary adults ages 57-75 were randomized into a physical training or a wait-list control group. The physical training group participated in supervised aerobic exercise on a stationary bike or treadmill for one hour, three times a week for 12 weeks. Participants' cognition, resting cerebral blood flow, and cardiovascular fitness were assessed at three time points: before beginning the physical exercise regimen, mid-way through at 6 weeks, and post-training at 12 weeks.

    Exercisers who improved their memory performance also showed greater increase in brain blood flow to the hippocampus. Using noninvasive brain imaging techniques, brain changes were identified earlier than memory improvements, implicating brain blood flow as a promising and sensitive metric of brain health gains across treatment regimens.

    "Physical exercise may be one of the most beneficial and cost-effective therapies widely available to everyone to elevate memory performance. These findings should motivate adults of all ages to start exercising aerobically. In another recent study, we have shown that complex mental training increases whole brain blood flow as well as regional brain blood flow across key brain networks. The combination of physical and mental exercise may be the best health measures to improve overall cognitive brain health. We have just begun to test the upper boundaries of how we can enhance our brain's performance into late life."

    Shorter term aerobic exercise improves brain, cognition, and cardiovascular fitness in aging

    Physical exercise, particularly aerobic exercise, is documented as providing a low cost regimen to counter well-documented cognitive declines including memory, executive function, visuospatial skills, and processing speed in normally aging adults. Prior aging studies focused largely on the effects of medium to long term (more than 6 months) exercise training; however, the shorter term effects have not been studied. In the present study, we examined changes in brain blood flow, cognition, and fitness in 37 cognitively healthy sedentary adults (57-75 years of age) who were randomized into physical training or a wait-list control group.

    The physical training group received supervised aerobic exercise for 3 sessions per week 1 h each for 12 weeks. Participants' cognitive, cardiovascular fitness and resting cerebral blood flow (CBF) were assessed at baseline (T1), mid (T2), and post-training (T3). We found higher resting CBF in the anterior cingulate region in the physical training group as compared to the control group from T1 to T3. Cognitive gains were manifested in the exercise group's improved immediate and delayed memory performance from T1 to T3 which also showed a significant positive association with increases in both left and right hippocampal CBF identified earlier in the time course at T2.

    These data suggest that even shorter term aerobic exercise can facilitate neuroplasticity to reduce both the biological and cognitive consequences of aging to benefit brain health in sedentary adults.


    Cryonics is a process of low-temperature preservation for your brain (and optionally body) on death. Cryoprotectant chemicals are infused into your tissues during a cooling process so as to produce a glass-like vitrification rather than freezing, minimizing formation of ice crystals and preserving the fine neural structures that contain the data of your mind. At some point in the future it will become possible to revive and restore an individual to life from even as radical a procedure as this. The technologies needed can currently be envisaged: swarms of guided nanomachines capable of repairing and altering cellular structures down to the level of individual proteins, combined with near-complete control over the growth, state, and behavior of cells that will evolve from present day stem cell research.

    The process of cryopreservation is not something that can be thrown together at the drop of a hat. Preparation is needed. This is especially true because we cannot legally choose the time our own death, and thus much of the expense and complexity of cryonics involves standby teams and the uncertainty inherent in the process of natural death. It is an ugly thing that the responsible, individual choice of assisted euthanasia is forbidden in our society. It forces people to suffer needlessly in their final, frail days, and further creates an entirely avoidable increase in expense and decrease in reliability of cryopreservation.

    Cryonics standby groups are often volunteers, and they go above and beyond to make cryopreservations happen even under the least optimal of circumstances, just as do the staff at organizations such as Alcor and the Cryonics Institute. All too many people fail to carry out the necessary preparations, and someone ends up having to pick up the slack. In a better world than this cryonics would be a large enough business to spur the creation of intermediaries who fulfill a role similar to that of insurance companies merged with paramedical organizations, working to ensure better end of life treatment and organization for cryonics patients. Unfortunately we do not yet live in that world, and so there are examples such as this:

    Alcor's 118th Patient

    A-2694 completed sign-up paperwork just four days before being pronounced and we confirmed receipt of payment for his cryopreservation on the day of pronouncement. The patient was admitted to a hospital in the Czech Republic on Wednesday October 23. Initially, a relative told us that doctors had claimed that conducting cryopreservation procedures in that country would be illegal. That turned out to be incorrect, although there is a requirement to conduct a postmortem. Fortunately, either because of the patient's dual citizenship or because a close relative was physically present to dismiss that requirement, no postmortem was required. Although payment for cryopreservation had not yet been received, the patient's brother had the wisdom to wire sufficient funds to allow us to begin preparations (with the invaluable assistance of international funeral directors Rowland Brothers in London) and to send Medical Response Director Aaron Drake to the Czech Republic.

    We had hoped to perform a field cryoprotection for the first time. This would have allowed us to cryoprotect the patient and ship him on dry ice. Just recently, we had positioned supplies in England for this purpose. Unfortunately, this turned out to be impossible. In part, this was due to the extremely close time frame for the patient's sign-up. More critically, however, we ran into incredibly bad luck in that on the day our supplies were to be moved from England to the patient's location, England was hit by the massive St. Jude storm. Winds of up to 80 mph led to cancelled flights and other major travel disruptions. Even if the patient had been well enough to move him to Germany (as we had suggested), field cryoprotection would not have been feasible.

    The patient's location in the Czech Republic added further difficulties. It turned out that the hospital lacked any ice facilities - a situation that would never happen in a US hospital. When the patient's condition (based on very limited medical information) seemed to be critical, Aaron Drake got on a flight to the Czech Republic on Sunday October 27. The patient was pronounced while Aaron was still in transit, then placed in the hospital morgue at around 2 degrees Celsius. All the dry ice in the area was purchased and used to cool and pack the patient for air transport to Alcor. A-2694 arrived at Phoenix Sky Harbor International Airport early in the evening of Friday November 1 and at Alcor around 9:00 pm. The transfer into cool down took a little over an hour. At the time of writing (November 7), the patient is close to completing the cool down process.

    Don't leave your preparations to the last minute. By doing so you make tightly-run organizations stretch themselves on your behalf: they will do their best at short notice, as happened here, but the end result may still be a poor cryopreservation. The preservation process needs to begin as soon as possible after death, and any delay is not a good thing: perhaps the damage accrued might be repairable by far-future technology, but there is every likelihood that it might not, as much of the vital data that makes up you as an individual is lost. That might as well be death.


    The protein signaling mechanisms surrounding insulin and insulin-like growth factor (IGF-1) are one of the better studied portions of the overlap between metabolic biochemistry and natural variations in longevity. They influence all of the core aspects of our biology: growth, regeneration, and other vital cell activities. Thus despite the years of work researchers still lack a truly clear picture of how it all fits together: this is a ferociously complex area of study, in which every molecular mechanism influences many other molecular mechanisms. Isolating any one portion of the interlinked systems making up the biology of life is next to impossible.

    Another comparatively well-studied and related area is autophagy, the collection of quality control processes by which cells clear out damaged components and unwanted waste compounds. More autophagy is consistently linked to enhanced longevity in laboratory animals, and shows up as a candidate mechanism for the extended life generated by a range of genetic alterations and environmental changes, such as the practice of calorie restriction. This makes sense: aging is most likely nothing more than an accumulation of damage, and more autophagy means less of that damage accumulating per unit time. Many researchers think that when it comes to slowing aging all roads lead to improved autophagy. Surprisingly, there hasn't been as much of a drive to produce autophagy-enhancing drugs as I would have expected by this time, despite some quite compelling demonstrations of the restored organ function that could be produced in old patients.

    Here we have research that bridges the two regions of study I've sketched above: tracing the alterations to metabolism that link insulin and insulin-like signaling with autophagy.

    Protein interplay in muscle tied to life span

    Fruit flies are notoriously short-lived but scientists interested in the biology of aging in all animals have begun to understand why some fruit flies live longer than others. They have documented a direct association between insulin and life span, for example, and have observed a tradeoff between prolific reproduction and longevity. A new study, which may have broad implications across species, ties those findings more closely together by tracing an insulin signaling cascade through to protein quality control in muscle tissue and shortened life span.

    The central feature of the study [is] the newly discovered role of the fruit fly equivalent of the mammalian protein complex activin. They found that it blocks the natural mechanism in muscle cells for cleaning out misfolded proteins, leading to a decline in muscle performance. In what [scientists] think is no coincidence, blocking the activity of that activin equivalent, called dawdle, can lengthen a fly's life span by as much as 20 percent, about 10 days.

    Activin Signaling Targeted by Insulin/dFOXO Regulates Aging and Muscle Proteostasis in Drosophila

    It is widely known that reduced insulin/IGF signaling slows aging in many contexts. This process requires the forkhead transcription factor (FOXO). FOXO modulates the expression of many genes, and the list of those associated with slow aging is impressive. But there are few data indicating the mechanisms or genes through which FOXO actually slows aging. Here, we identify a novel FOXO target, dawdle, the Activin-like ligand in fruit flies.

    Activin signaling through the Smad binding element inhibits the transcription of Autophagy-specific gene 8a (Atg8a) within muscle, a factor controlling the rate of autophagy. Expression of Atg8a within muscle is sufficient to increase lifespan.

    These data reveal how insulin signaling can regulate aging through control of Activin signaling that in turn controls autophagy, representing a potentially conserved molecular basis for longevity assurance. While reduced Activin within muscle autonomously retards functional aging of this tissue, these effects in muscle also reduce secretion of insulin-like peptides at a distance from the brain. Reduced insulin secretion from the brain may subsequently reinforce longevity assurance through decreased systemic insulin/IGF signaling.

    Not surprisingly, the details uncovered by these researchers have the look of a two-way feedback loop. Little in biology is a one-way street, which is one of the many reasons it is very hard to even understand the metabolism of longevity, let alone safely alter it. The existence of this complexity is why I favor strategies for enhancing longevity that do not rely upon altering an aged metabolism, but instead aim to restore it to a youthful state by repairing damage. This is an important distinction to make, and it will become ever more important in the years ahead.


    Monday, November 11, 2013

    Researchers here take a novel approach to produce accelerated healing in laboratory animals, and go some way towards identifying the mechanisms involved, which link portions of the immune system and gut microbe ecosystem with healing capacity. It is possible that the immune system component of this research will yield ways to patch over progressive age-related dysfunction in those aspects of immune function associated with healing.

    Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals.

    Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host immune T regulatory cells conveying transplantable wound healing capacity.

    This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

    Monday, November 11, 2013

    Too many people take it as read that there are too many people. The assumption of overpopulation as a reality is the great myth of our time, held despite the obvious figures on the table to show that this planet of ours could comfortably support many multiples of the present population even with today's technology. It is the legacy of the success of the environmentalist movement, which transcended the reasonable portions of the original agenda to transform itself into something of a civic religion somewhere along the way. It is a strange twist to the cultures we create to see that the average person in the street now thinks that many of our greatest achievements should be torn down or relinquished and even that human existence is a net negative.

    Yet where there is poverty and suffering, that state exists despite present wealth and opportunities to generate wealth, not because of the number of people involved. There is more than enough food, more than enough resources, and more of an excess of both are being created with each passing year. These are political and distribution issues, problems of organization, kleptocracy, and simple inhumanity. Waste amid the potential for plenty.

    The prevalence of the overpopulation myth is, I think, one of the important contributing factors to public opposition to extending healthy human life span. Much of the public is convinced that there exists a present crisis of population that will lead inevitably to some form of resource collapse - which is far from the case, but facts in evidence never played much of a role in these sorts of slow-moving hysteria in the past. These patterns of belief even extend into the community of futurists and supporters of longevity science, and hence you'll sometimes see articles such as this one:

    When our most precious and hard fought for successes give rise to yet more challenges life is revealing its Sisyphean character. We work as hard as we can to roll a rock up a hill only to have it crush us on the way down. The stones that threatens us this time are two of our global civilization's greatest successes - the fact that children born are now very likely to live into old age and the fact that we have stretched out this old age itself so that many, many more people are living into ages where in the past the vast majority of their peers would be dead. These two demographic revolutions when combined form the basis of what I am calling the Longevity Crisis.

    Ultimately in terms of the sustainability of our species [the present] decline in the birth rate is a very good thing. Demographics, however, is like a cruise ship - it is hard to turn. In the lag time the world's population is exploding as societies are able to save the lives of children but continue to have nearly as many of them. We are living through the turning. [It] took humanity roughly 250,000 years to reach 1 billion of us in 1900, but thereafter the rate of growth skyrocketed. There was only a little over a century between our first billion and second billion. 40 years later in 1960 we numbered 3 billion. Only 14 years after that we reached the 4 billion mark and the time between adding another billion would shorten to about a mere dozen years with 5 billion reached in 1987, 6 billion following 12 years later in 1999, and 7 billion a dozen after that in 2011.

    Thankfully, the rate of population growth is slowing. It will take us 14 years to pass the 8 billion mark and 20-25 years to reach what will perhaps be the peak of human population during this era - 9 billion in 2050. Though comforting we shouldn't necessarily be sanguine in light of this fact - we are still on track to add to the world the equivalent of another China and Europe by the middle of the century. Certainly, these people will, with justice, hanker after a middle class lifestyle putting enormous pressures on the global environment. Add to that the effects of climate change and it seems we are entering a very dangerous and narrow chute through which humanity must pass.

    Some people feel threatened by large numbers. But numbers alone mean nothing and say nothing. They carry no information or context, and to base fear of the future rather than optimism on the fact that one number is changing is an emotional reaction, not a rational analysis.

    Tuesday, November 12, 2013

    Researchers here argue that calorie restriction extends life in nematode worms by causing mitochondria to emit more reactive oxygen species, which leads to a reaction from neurons that sense this higher level of oxidative stress. Their evidence is fairly compelling: we'll have wait and see how this can be reconciled with the good evidence for the benefits of calorie restriction in mammals to derive at least in part from loss of visceral fat tissue and sensing of levels of methionine.

    Dietary restriction (DR) extends lifespan and promotes metabolic health in evolutionary distinct species. DR is widely believed to promote longevity by causing an energy deficit leading to increased mitochondrial respiration. We here show that inhibitors of mitochondrial complex I promote physical activity, stress resistance as well as lifespan of Caenorhabditis elegans despite normal food uptake, i.e. in the absence of DR. However, complex I inhibition does not further extend lifespan in dietarily restricted nematodes, indicating that impaired complex I activity mimics DR.

    Promotion of longevity due to complex I inhibition occurs independently of known energy sensors, including DAF-16/FoxO, as well as AAK-2/AMPK and SIR-2.1/sirtuins, or both. Consistent with the concept of mitohormesis, complex I inhibition transiently increases mitochondrial formation of reactive oxygen species (ROS) that activate PMK-1/p38 MAP kinase and SKN-1/NRF-2. Interference with this retrograde redox signal as well as ablation of two redox-sensitive neurons in the head of the worm similarly prevents extension of lifespan.

    These findings unexpectedly indicate that DR extends organismal lifespan through transient neuronal ROS signaling rather than sensing of energy depletion, providing unexpected pharmacological options to promote exercise capacity and healthspan despite unaltered eating habits.

    Tuesday, November 12, 2013

    There is plenty of evidence to suggest that variations in human longevity are to some degree inherited, though there is also a great deal of room to argue over which mechanisms might be involved. Here is another research result to add to existing data on this subject:

    Offspring of long-lived individuals have lower risk for dementia. We examined the relation between parental longevity and cognition and subclinical markers of brain ageing in community-dwelling adult offspring. Offspring participants with both parents in the Framingham Heart Study, aged ≥55 years and dementia-free underwent baseline and repeat neuropsychological (NP) testing and brain magnetic resonance imaging (MRI). Parental longevity was defined as having at least one parent survive to age ≥85 years.

    Of 728 offspring (mean age 66 years, 54% women), 407 (56%) had ≥1 parent achieve longevity. In cross-sectional analysis, parental longevity was associated with better scores on attention and a lower odds of extensive white matter hyperintensity on brain MRI. The association with white matter hyperintensity was no longer significant in models adjusted for cardiovascular risk factors and disease.

    In longitudinal analysis (6.7 ± 1.7 years later), offspring with parental longevity had slower decline in attention, executive function and visual memory, and less increase in temporal horn volume. The associations persisted in fully adjusted models.

    Wednesday, November 13, 2013

    One approach to mimic the effects of calorie restriction is to replace an important molecular component of the diet with some other substance that cannot be processed in the necessary ways by an individual's metabolism. This is easier to achieve in lower animals, and here is an example of the way in which researchers use this and other simple ways to extend life in order to narrow down the search for the genes and mechanisms by which metabolism determines longevity:

    Glucose restriction mimicked by feeding the roundworm Caenorhabditis elegans with 2-deoxy-D-glucose (DOG) - a glucose molecule that lacks the ability to undergo glycolysis - has been found to increase the life span of the nematodes considerably.

    To facilitate understanding of the molecular mechanisms behind this life extension, we analyzed transcriptomes of DOG-treated and untreated roundworms obtained by RNA-seq at different ages. We found that, depending on age, DOG changes the magnitude of the expression values of about 2 to 24 percent of the genes significantly, although our results reveal that the gross changes introduced by DOG are small compared to the age-induced changes. We found that 27 genes are constantly either up- or down-regulated by DOG over the whole life span, among them several members of the cytochrome P450 family.

    The monotonic change with age of the temporal expression patterns of the genes was investigated, leading to the result that 21 genes reverse their monotonic behaviour under impaired glycolysis. Put simply, the DOG-treatment reduces the gross transcriptional activity but increases the interconnectedness of gene expression. However, a detailed analysis of network parameters discloses that the introduced changes differ remarkably between individual signalling pathways. We found a reorganization of the hubs of the mTOR pathway when standard diet is replaced by DOG feeding.

    By constructing correlation based difference networks, we identified those signalling pathways that are most vigorously changed by impaired glycolysis. Taken together, we have found a number of genes and pathways that are potentially involved in the DOG-driven extension of life span of C. elegans. Furthermore, our results demonstrate how the network structure of ageing-relevant signalling pathways is reorganised under impaired glycolysis.

    Wednesday, November 13, 2013

    Cells continually accumulate damage in the form of metabolic waste products and broken or misfolded protein machinery. Several systems toil to remove this damage on an ongoing basis, and the efficiency of these systems is linked to longevity: more cellular housekeeping is a good thing. Unfortunately, and as is the case for all aspects of our biology, these housekeeping processes become less efficient with age, most likely overwhelmed by forms of damage and waste products that they cope poorly with.

    You might be familiar with the lysosome and its role in recycling damaged cellular components, and know that lysosomal activity declines with aging due to a build up of hardy waste compounds that our biology isn't equipped to break down. There are other components of the housekeeping system in our cells, however, and they also fail with age. Just as there are potential means to restore lysosomal recycling to youthful efficiency, so too will there be ways to rejuvenate these other housekeeping systems. For example, here researchers demonstrate restoration of the effectiveness of the ubiquitin-proteasome system, important in the clearance of misfolded proteins:

    Levels of damaged proteins increase with the age of different species, including fungi, flies, worms, bats, birds, rodents, and humans. Several principal possibilities have been suggested to explain this apparently universal accumulation of damaged/misfolded proteins, including a diminished capacity for protein quality control, which encompasses the removal of damaged and misfolded proteins by the proteasome. Indeed, the function of the 26S proteasome decreases during aging in several human tissues, senescent primary cultures, and whole organisms, pinpointing the proteasome as a possible malefactor behind age-related damage propagation.

    Here, using yeast as a model system, we show that while the level and potential capacity of the 26S proteasome is maintained in replicatively aged cells, the UPS is not functioning properly in vivo. As a consequence cytosolic UPS substrates are stabilized, accumulate, and form inclusions.

    By integrating a PGPD-HSP104 recombinant gene into the genome, we were able to constitutively elevate protein disaggregase activity, which diminished the accumulation of protein inclusions during aging. Remarkably, this elevated disaggregation restored degradation of a 26S proteasome substrate in aged cells without elevating proteasome levels, demonstrating that age-associated aggregation obstructs UPS function. The data supports the existence of a negative feedback loop that accelerates aging by exacerbating proteostatic decline once misfolded and aggregation-prone proteins reach a critical level.

    Thursday, November 14, 2013

    The cardiovascular system loses its flexibility with age, a process thought to be related to a build up of cross-links, calcium deposits, and other unwanted compounds in the extracellular matrix. Reversing this portion of age-related degeneration should be a comparatively straightforward matter of building drugs to break down or remove these metabolic byproducts. Researchers here investigate another possible culprit in the process:

    Heart valves calcify over time, and [scientists] are beginning to understand why. [They] found through studies of pigs' heart valves that age plays a critical role in the valves' progressive hardening, and the problem may be due to the infiltration of a protein known as von Willebrand factor (VWF). VWF helps regulate blood clotting in both pigs and humans but [it] finds its way over time into the collagen-rich interior of the valve tissues. Because clotting is not an issue in collagen, there is no apparent need for VWF to be present. The researchers went looking for a connection to the calcium nodules that form in the tissues and make the valves' leaflets less flexible, which decreases blood flow to the heart.

    [Researchers] tested how valve interstitial cells that produce calcium nodules in diseased valves respond to VWF. When interstitial cells were intentionally exposed to VWF, "there was a dramatic increase in the size of the nodules at every age. Endothelial cells on the outside of the valve are making most of these (clotting-related) proteins. We found they don't just float away into the blood or stay on the valve surface. Some of them penetrate down into the tissue."

    What remains to be seen is why. Heart valves are in motion from birth to death and are perhaps the most active connective tissue in the body. The researchers suspect the breakdown of collagen over time, as well as the constant stretching of the valve, opens gaps through which the proteins can travel. "As you get older, collagen becomes less organized. Because the distinct arrangement of extracellular matrix disappears, I think proteins like VWF permeate inside the valve more than what you would see in young, healthy adults."

    Thursday, November 14, 2013

    Is medical research funding at all rational in its amounts and distributions? Well, no, evidently not, since SENS rejuvenation research is not a billion dollar a year field, and all current research aimed at producing better ways of treating or eliminating age-related disease taken together is a tiny economic activity when compared to, say, making candy or small collectible dolls. But even within the existing research and funding community, it can be argued that priorities do not align with a utilitarian approach to aging and age-related disease:

    The global population is aging and although age remains the primary risk factor for all major causes of death, no priorities for aging research exist. After reviewing the literature on mortality modelling we found that different chronic processes underlie mortality before and after reproductive age. To identify priorities in aging research, we propose a simple ranking method that uses the percentage of deaths attributable to each disease for the over-60 population, on the basis that, rather than being the result of individual risk factors, these deaths are largely due to underlying senescent processes.

    Our ranking suggests that vascular aging, led by ischaemic heart disease and stroke, is the most important focus for aging research. The availability of funding, however, is not currently aligned with health priorities and we believe that rectifying this disconnect may improve societal health outcomes.

    Friday, November 15, 2013

    Accumulating excess fat tissue is bad for you. The mechanisms might derive largely from the presence of visceral fat tissue, which causes chronic inflammation and large changes in the operation of metabolism, leading to metabolic syndrome. It is also possible that other mechanisms related to nutrient sensing are at work, shifting portions of your biology into a fast-aging mode that evolved in some common ancestor to accelerate reproduction in times of plenty. Equally, being overweight tends to accompany sedentary behavior, and lack of exercise is very harmful to long-term health.

    Regardless, it seems like a good idea to avoid becoming fat: the weight of evidence to show that it will harm your future health is heavy indeed, especially when it comes to cardiovascular disease:

    Overweight and obesity likely cause myocardial infarction (MI) and ischemic heart disease (IHD); however, whether coexisting metabolic syndrome is a necessary condition is unknown. To test the hypothesis that overweight and obesity with and without metabolic syndrome are associated with increased risk of MI and IHD [we] examined 71,527 individuals from the Copenhagen General Population Study and categorized them according to body mass index (BMI) as normal weight, overweight, or obese and according to absence or presence of metabolic syndrome.

    For MI, multivariable adjusted hazard ratios vs normal weight individuals without metabolic syndrome were 1.26 in overweight and 1.88 in obese individuals without metabolic syndrome and 1.39 in normal weight, 1.70 in overweight, and 2.33 in obese individuals with metabolic syndrome. For IHD, results were similar but attenuated. Among individuals both with and without metabolic syndrome there were increasing cumulative incidences of MI and IHD from normal weight through overweight to obese individuals.

    These findings suggest that overweight and obesity are risk factors for MI and IHD regardless of the presence or absence of metabolic syndrome and that metabolic syndrome is no more valuable than BMI in identifying individuals at risk.

    Friday, November 15, 2013

    Below is quoted a mainstream media piece on Dmitry Itskov's 2045 Initiative, an exemplar of that section of the futurist community who look forward to non-biological strategies for extending life. The underlying goals of reverse engineering the brain, building brain simulations, and integrating technology with neural tissue and functions are very much in the air these days, and a number of large US and European projects are underway in this space.

    At the tender age of 32, Dmitry Itskov is not yet a billionaire, although a lot of respected news outlets think otherwise. He is a millionaire many times over - a survivor of the dot-com bubble who made his fortune building a media empire in Russia. Like many people who become extremely rich very quickly, he has decided to invest some of his money in innovative, forward-looking endeavors. But his idea is more ambitious than most: radical life extension.

    In 2011, Itskov founded the 2045 Initiative, which is named for the year when he intends to complete the project's ultimate goal: to outwit and outrun mortality itself. His "avatar" project is a four-stage process, beginning with the development of androids directed by brain-computer interfacing - mind-controlled robots, in other words. It would culminate in a computer model of a person's brain and consciousness, which could be uploaded into a machine for posterity. An eternal problem, solved.

    To achieve cybernetic immortality and turn what he calls his "science mega-project" into a reality, Itskov's 2045 Initiative is funding labs around the world; Itskov is both investing his own money and raising external capital, building support among entities ranging from Ivy League universities to large corporations to even the Dalai Lama. Even if Itskov doesn't reach his final goal of radical life extension via avatars, the amount of attention he's bringing and money he's investing in neurotech research have many people excited. And Itskov is just one in an increasingly crowded field.

    While I don't agree that the end goal here is useful from a practical standpoint - a copy of you is not you - the next few decades are certainly going to be a very interesting time in applied neurotechnology.


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