Fight Aging! Newsletter, December 24th 2012

December 24th 2012

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!



- 2012 Holiday Newsletter from the SENS Research Foundation
- From the Methuselah Foundation: 2012, the Year in Review
- Overexpression of BubR1 Extends Life in Mice
- Years of Life Gained Through Leisure-Time Activity
- An Introduction to What's Going On Inside Long-Lived Mice
- Discussion
- Latest Headlines from Fight Aging!
    - A Report From the Eurosymposium on Healthy Aging
    - Using Immune Cells to Deliver Cancer-Killing Viruses
    - Treating ALS With Neural Stem Cell Transplants
    - Removing Cellular Garbage to Treat Neurodegenerative Disease
    - Life is Change, and a Longer Life Means More Change
    - We Owe it to Our Ancestors to Pursue Greater Longevity
    - Immune Therapy Versus Brain Tumors
    - Digging Deeper into Nematode Longevity via Loss of Germ Cells
    - The International Longevity Alliance
    - Inducing the Formation of a New Biological Pacemaker


SENS Research Foundation's mission is to transform the way the world researches and treats the diseases of aging. As another holiday season approaches, we would like to share the progress that we have made with you. Our projects on lysosomal aggregates and mitochondrial mutations at our Mountain View, California research center have advanced steadily over the last year. We have also launched a major new project on the alternative lengthening of telomeres.

Meanwhile, we continued to expand our extramural programs, conducted in collaboration with such elite university partners as Harvard, Yale, Cambridge, and Berkeley. Our development work has also made great strides. You will soon see the results of a complete logo and website design overhaul, and the world-class animations that we have commissioned to visualize the individual strands of SENS.

All that said, you can be sure that the challenge we face remains daunting. Not a single one of the conditions that cause so much suffering and claim so many lives across the world - Alzheimer's, heart disease, and diabetes, to name a few - has yet been cured. We believe that the greatest promise to not simply treat but eradicate age-related disease lies in the use of regenerative medicine: the rejuvenation biotechnology approach.

Unfortunately, despite the increasingly large amount of data indicating the effectiveness of this approach, research on "damage repair" therapies remains largely neglected.
As a nonprofit research charity, we depend on your generosity to drive this critical work. Our level of funding determines how many new scientific projects we can sponsor, how loudly we can broadcast our message, and how many students we can educate about the SENS platform. We have come a long way with your help so far, and have many more steps that we can take.


n the spirit of the season, we've been looking back on the last year at Methuselah Foundation and appreciating everything we have to be thankful for. And we want you to know that you're at the top of the list. Without our many donors, colleagues, partners, and friends, we could never do what we do. We're so grateful for your ongoing support, and we'd like to thank you for believing so fervently, like we do, in the enormous promise of regenerative medicine for extending healthy human life.

Thanks to your generosity, Methuselah made significant progress in 2012 on our flagship project, the New Organ Prize. We launched a beta website at and kicked off our first campaign to raise $100,000 and inspire 100 people to become "New Organizers." We quadrupled the size of our online community at We're collaborating with the gifted filmmaker Michael Marantz (The Future is Ours) on a video highlighting regenerative medicine as a lasting solution to the organ crisis. We've been working with tissue engineering pioneers like Dr. Anthony Atala, Dr. Paolo Macchiarini, and Dr. Gabor Forgacs to beging shaping prize rules and criteria. And as we enter December, we're only $20,000 away from reaching our $100,000 goal for New Organ in 2012.

The field of regenerative medicine is truly coming of age, with growing public interest and more press coverage during the past six months than at any time we can remember. We even saw a Nobel Prize in Medicine this year for Dr. Shinya Yamanaka and Dr. John Gurdon's work on pluripotent stem cells. From all of us at the Methuselah Foundation, happy holidays, and thank you once again for everything you do. We're looking forward to sharing an even brighter 2013 with you.


Biologists report that genetically engineered mice that make extra BubR1 are less prone to cancer. For example, they found that when they exposed normal mice to a chemical that causes lung and skin tumors, all of them got cancer. But only 33% of those overexpressing BubR1 at high levels did. They also found that these animals developed fatal cancers much later than normal mice - after about 2 years, only 15% of the engineered mice had died of cancer, compared with roughly 40% of normal mice.

The animals that overexpressed BubR1 at high levels also lived 15% longer than controls, on average. And the mice looked veritably Olympian on a treadmill, running about twice as far - 200 meters rather than 100 meters - as control animals. All of this left [researchers] thinking that BuBR1's life-extending effects aren't due to only its ability to prevent cancer, although that's not yet certain.

BubR1 overexpression markedly reduced aneuploidy (a state of having an abnormal number of chromosomes), which causes birth defects. Other results showed these mice were protected from muscle fiber deterioration, that they were better performers in treadmill tests, that they had much reduced levels of renal sclerosis, intestinal fibrosis and tubular atrophy - all signs of aging. They also showed higher cardiac-stress tolerance and resistance to age-related retinal atrophy.


Data from the National Health and Nutrition Examination Survey (2007-2010); National Health Interview Study mortality linkage (1990-2006); and U.S. Life Tables (2006) were used to estimate and compare life expectancy at each age of adult life for inactive (no moderate to vigorous physical activity); somewhat-active (some moderate to vigorous activity); and active ([more] moderate to vigorous activity) adults. Analyses were conducted in 2012.

Somewhat-active and active non-Hispanic white men had a life expectancy at age 20 years that was ∼2.4 years longer than that for the inactive men; this life expectancy advantage was 1.2 years at age 80 years. Similar observations were made in non-Hispanic white women, with a higher life expectancy within the active category of 3.0 years at age 20 years and 1.6 years at age 80 years. In non-Hispanic black women, as many as 5.5 potential years of life were gained due to physical activity. Significant increases in longevity were also observed within somewhat-active and active non-Hispanic black men; however, among Hispanics the years-of-life-gained estimates were not significantly different from 0 years gained.

The estimates in the present study for non-Hispanic white men aged 20 years [suggest] that 2.6 hours [of overall life expectancy] are gained per hour of moderate activity and 5.2 hours were gained per hour of vigorous activity accrued in adulthood.


The remarkable extension of longevity in mice lacking GH or GH receptors appears to be due to multiple interacting mechanisms including reduced activation of growth-promoting pathways, greater stress resistance, reduced inflammation, increased reservoir of pluripotent stem cells, and improved genome maintenance.

Data summarized in this article indicate that alterations in energy metabolism and improved insulin control of carbohydrate homeostasis have to be added to this list. In fact, these metabolic adaptations may represent key features of the "longevous" phenotype of these animals and important mechanisms of the extension of both healthspan and lifespan in GH-related mutants.

Importantly, many of the metabolic features of long-lived mutant mice described in this article have been associated with extended human longevity. Comparisons between centenarians and elderly individuals from the same population and between the offspring of exceptionally long-lived people and their partners indicate that reduced insulin, improved insulin sensitivity, increased adiponectin, and reduced pro-inflammatory markers consistently correlate with improved life expectancy.


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



Friday, December 21, 2012
The Eurosymposium on Healthy Aging took place in Brussels earlier this month, a gathering of researchers and advocates for longevity science. The presentations were recorded and videos have been posted to Youtube. I encourage you to browse. Here is a report on the event: "Theoretical questions of longevity were covered in the first day, including such themes as the general overviews of ageing theories, molecular damage in ageing, mitochondria and autophagy. The general panel on causes, mechanisms, and interventions in aging, featured Drs. Aubrey de Grey, David Gems, Kris Verburgh, and Diana Van Heemst, and was moderated by Sven Bulterijs of HEALES. The second day featured an inspiring plethora of promising potential interventions for increasing healthy longevity: genetics of aging and centenarians research, nutritional and pharmacological interventions in aging, biomedical interventions such as repair of damaged mitochondria, destruction of senescent cells, use of telomerase to extend health span, remediation of the Alzheimer's disease, and regenerative medicine, including both cell material and computational aspects. The main subject of the third day was the political and social promotion of research into the biology of aging and healthy longevity. Discussion groups were formed and tentative suggestions made for increasing funding for life extension research, improving public opinion of life extension, and scientific positioning of life-extension."

Friday, December 21, 2012
A successful demonstration of a novel form of immune therapy is noted in this article, and described in a recently published paper: "An experimental "Trojan-horse" cancer therapy has completely eliminated prostate cancer in experiments on mice. [The] team hid cancer killing viruses inside the immune system in order to sneak them into a tumour. [After] chemotherapy or radiotherapy is used to treat cancer, there is damage to the tissue. This causes a surge in white blood cells, which swamp the area to help repair the damage. "We're surfing that wave to get as many white blood cells to deliver tumour-busting viruses into the heart of a tumour." [Researchers] blood samples and extract macrophages, a part of the immune system which normally attacks foreign invaders. These are mixed with a virus which, just like HIV, avoids being attacked and instead becomes a passenger in the white blood cell. In the study, the mice were injected with the white blood cells two days after a course of chemotherapy ended. At this stage each white blood cell contained just a couple of viruses. However, once the macrophages enter the tumour the virus can replicate. After about 12 hours the white blood cells burst and eject up to 10,000 viruses each - which go on to infect, and kill, the cancerous cells. At the end of the 40-day study, all the mice who were given the Trojan treatment were still alive and had no signs of tumours. By comparison, mice given other treatments died and their cancer had spread."

Thursday, December 20, 2012
Many of the early forms of stem cell therapy involve cell transplants, and seem to produce benefits without those transplanted cells creating replacements for lost native cells. Instead the newcomers are improving the local environment and issuing signals that allow greater survival and repair among the native cell populations. Here is an example of the type: "Promising new research provides evidence that amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, may be treatable using neural stem cells. A consortium of researchers at multiple institutions [have] shown that neural stem cells, when transplanted into the spinal cord of a mouse model with familial ALS, slow disease onset and progression while improving motor function, breathing and survival time compared to untreated mice. Neural stem cells are the precursors of all brain cells. They can self-renew, making more neural stem cells, and differentiate, becoming nerve cells or other brain cells. These cells can also rescue malfunctioning nerve cells and help preserve and regenerate brain tissue. But they've never before been studied extensively in a good model of adult ALS. In 11 independent studies [researchers] transplanted neural stem cells into the spinal cord of a mouse model of ALS. The transplanted neural stem cells benefited the mice with ALS by preserving the health and function of the remaining nerve cells. Specifically, the neural stem cells promoted the production of protective molecules that spared remaining nerve cells from destruction. They also reduced inflammation and suppressed the number of toxin-producing and disease-causing cells in the host's spinal cord."

Thursday, December 20, 2012
Improving the ability of cells to clear out garbage is a potential therapy for a wide range of conditions - probably including aging itself, as the failure of garage clearance mechanisms related to the lysosome contributes to degenerative aging. In past years researchers have noted that calorie restriction seems to boost garbage clearance and the cellular recycling known as autophagy, while making autophagy more efficient has been used to rejuvenate liver function in old mice. Here researchers are tinkering with garbage clearance in the brain as a way to treat neurodegenerative conditions, many of which seem to involve a buildup of unwanted and harmful compunds inside cells: "[Researchers] found that the issue in amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD) is the inability of the cell's protein garbage disposal system to "pull out" and destroy TDP-43, a powerful, sometimes mutated gene that produces excess amounts of protein inside the nucleus of a nerve cell, or neuron. The way to rev up protein disposal is to add parkin - the cell's natural disposal units - to brain cells. In this study, [researchers] demonstrated in two animal experiments that delivering parkin genes to neurons slowed down ALS pathologies linked to TDP-43. [The] study further demonstrates that clumps known as "inclusions" of TDP-43 protein found inside neuron bodies in both disorders do not promote these diseases, as some researchers have argued. What happens in both diseases is that this protein, which is a potent regulator of thousands of genes, leaves the nucleus and collects inside the gel-like cytoplasm of the neuron. In ALS, also known as Lou Gehrig's disease, this occurs in motor neurons, affecting movement; in FTD, it occurs in the frontal lobe of the brain, leading to dementia. "Our study suggests TDP-43 in the cell cytoplasm is deposited there in order to eventually be destroyed - without contributing to disease - and that TDP-43 in the nucleus is causing the damage. Because so much protein is being produced, the cell can't keep up with removing these toxic particles in the nucleus and the dumping of them in the cytoplasm. There may be a way to fix this problem." [Researchers] found that parkin "tags" TDP-43 protein in the nucleus with a molecule that takes it from the nucleus and into the cytoplasm of the cell. "This is good. If TDP-43 is in the cytoplasm, it will prevent further nuclear damage and deregulation of genetic materials that determine protein identity, We think parkin is tagging proteins in the nucleus for destruction, but there just isn't enough parkin around - compared with over-production of TDP-43 - to do the job.""

Wednesday, December 19, 2012
Change is coming, more of it in the next few decades than has taken place in the past few centuries: progress is accelerating. We are the species that builds and changes - but inside we still carry the evolved instincts of the ape, and he greatly dislikes change, no matter whether or not it is positive. How much of opposition to human life extension is predicated on fear of change? ""Wouldn't you eventually get bored?" Like clockwork, the question arises when I tell someone quixotically, arrogantly, that I plan on living forever. From the limited perspective of 20 years, even the prospect of living another six or seven decades in full color can be impossible to envisage. Hedging, I answer that assuming a world where radical life extension is possible, there will be no telling as to how different the human experience will be from what we know. Returning to the original question - in essence: "Why choose to live forever if forever really just means eternal boredom and senescence?" - it's apparent that living forever would mean something other than continuing as our current selves. Technology futurists are reasonably certain that at some point in the next century, we'll be enmeshed in networks of artificial intelligence, bodily modified beyond immediate recognition, and confronted with a new set of identity questions, societal challenges, and existential ambitions. If I'm fortunate enough to make it to 150, I expect to find a world where caring about ethnic politics in the Middle East, wearing university colors, impressing girls, and investigating my ancestral origins won't be of much, if any, use. In other words, I expect that I'll need to invent a new self for a radically new world. More than anything I can imagine, it'll be a tall order. We have good evolutionary reason to love ourselves to death rather than contemplate being completely reconfigured. It's a daunting prospect to imagine, but it's anything but boring."

Wednesday, December 19, 2012
In the past I've discussed whether or not we are obliged to future generations, morally bound to work on making their world a better place by producing rejuvenation biotechnologies. Here, it is suggested that we are obliged to past generations - that we owe much to their efforts to improve the human condition and should thus continue to do the same, as a sign of respect at the very least: "Humanity has braved the weather many times over the millennia, surviving long enough to invent language, an earth-shattering breakthrough in their time. Language to them was as big of a game changing breakthrough than the internet is to the world now. We pushed on through famines and wars, the cold, the heat, the wild. We figured out how to harness fire. We learned how to farm so we could live in greater abundance. That gave rise to more free time to invent and explore, and led us through progressions like the bronze and iron ages. This in turn enabled so many other things eventually leading up through times like the great industrial age. Humanity exponentially shifted a gear soon after, and moved on through the technology revolution. The struggle and strife and hardship and toil that has been gone through to get us here is deeper than I can imagine. I try sometimes, as many of you might also, and its horrifying. The world is filled with graveyards; the soil is drenched in blood, sweat and tears. The dreams realized and the dreams shattered echo across the millennia and eons. If we could have collected all the hardship on video to play it in a huge montage then I imagine it might kill us from strife. We owe this to them, we owe the creation of indefinite life spans to them. They have brought us through all that to this great cusp of destiny. We grab the baton, on the ground work that our ancestors put down for us, with their blood coursing through our veins. [They] had to die for us to be here. They had to give us all that they did and then die so that we may have what we have. We don't have what we have because it magically appeared here. We have it because they toiled and died for us to have it. We cannot pilfer it and waste the opportunity, we have to keep pioneering existence, we have to keep building, we have to keep pushing the boundaries, because that is the wage they earned."

Tuesday, December 18, 2012
Cancer immunotherapy technology demonstrations continue to roll in. This one is representative of what is taking place in many laboratories these days: "Using an artificial protein that stimulates the body's natural immune system to fight cancer, a research team [has] engineered a lethal weapon that kills brain tumors in mice while sparing other tissue. If it can be shown to work in humans, it would overcome a major obstacle that has hampered the effectiveness of immune-based therapies. The protein is manufactured with two arms - one that exclusively binds to tumor cells and another that snags the body's fighter T-cells, spurring an attack on the tumor. In six out of eight mice with brain tumors, the treatment resulted in cures. "This work represents a revival of a somewhat old concept that targeting cancer with tumor-specific antigens may well be the most effective way to treat cancer without toxicity. But there have been problems with that approach, especially for brain tumors. Our therapeutic agent is exciting, because it acts like Velcro to bind T-cells to tumor cells and induces them to kill without any negative effects on surrounding normal tissues. One of the major advantages is that this therapy can be given intravenously, crossing the blood-brain barrier. When we gave the therapy systemically to the mice, it successfully localized to the tumors, treating even bulky and invasive tumors in the central nervous system.""

Tuesday, December 18, 2012
If you remove germ cells from nematode worms or flies they live longer. Researchers continue to investigate the mechanisms involved: "The gonad is well known to be important for reproduction but also affects animal life span. Removal of germ cells - the sperm and egg producing cells - increases longevity of the roundworm Caenorhabditis elegans. However, the underlying molecular mechanisms were a mystery. [The] roundworm Caenorhabditis elegans is a commonly used model organism in the field of ageing research. It develops from an egg to adult through four larval stages. These developmental stages are controlled by a developmental clock. [Researchers] used a laser to remove the germ cells. They found that the remaining gonadal cells trigger production of a steroid hormone called dafachronic acid. Dafachronic acid activates so-called microRNAs, which work as tiny molecular switches causing changes in gene expression that promote longevity. Interestingly, this same steroid hormone-microRNA switch was previously shown [to] be part of the developmental clock. Thus, the loss of the germ cells ultimately causes the worm to use developmental timers to put in motion a life-prolonging programme."

Monday, December 17, 2012
This past year, efforts have started in the longevity science community to form single-issue political parties in Russia and some European Union countries. This is a long-standing form of advocacy in that part of the world, where political systems are structured in such a way that having a formal party - even if small - opens the door to reaching more people with your message. Successful examples from past years include the Green Party and the Pirate Party. The various newly-founded longevity party initiatives have a unified banner organization called the International Longevity Alliance. That group recently launched their website: "The International Longevity Alliance promotes the social struggle against the deteriorative aging process and for healthy and productive longevity for all, through scientific research, technological development, medical treatment, public health and education measures, and social activism. We believe that this goal can be achieved through broad public cooperation and support, from all nations and all walks of life. Hence, the International Longevity Alliance promotes the creation and international cooperation of social activist and advocacy groups from across the world. Advocacy Groups within the International Longevity Alliance have been initiated in more than 30 countries. Currently we are in the process of official registration as a non-profit, non-governmental international public association. Several options for registration are considered, mainly in the US and EU, that would ensure the optimal and egalitarian international cooperation. Petitions in support of research of aging and longevity are being promoted in the EU, US and Russia."

Monday, December 17, 2012
Researchers demonstrate the ability to guide heartbeats by introducing pacemaker cells: "A human heart is made up of billions of cells, but researchers say fewer than 10,000 are responsible for controlling the heartbeat. Age and disease can lead to problems such as the heart pumping too fast or too slow - and it can even stop completely, in what is known as a cardiac arrest. A team of [researchers] tried to restore the heart's own ability to dictate the beat by creating new pacemaker cells. They used a virus to infect heart muscle cells with a gene, called Tbx18, which is normally active when pacemaker cells are formed during normal development in an embryo. When heart cells were infected with the virus they became smaller, thin and tapered as they acquired the "distinctive features of pacemaker cells." When the virus was injected into a region of the hearts of seven guinea pigs, five later had heartbeats which originated from their new pacemaker. [Researchers expect] the same method to work in the human heart as they used a human gene, Tbx18, to generate the effect. "It opens up the tantalising possibility of using cell therapy to restore normal heart rhythm in people who would otherwise need electronic pacemakers. However, much more research now needs to be done to understand if these findings can help people with heart disease in the future.""



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