Fight Aging!

LONGEVITY MEME NEWSLETTER
February 7th 2011

The Longevity Meme 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 the Longevity Meme.

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CONTENTS

- Bisphosphonates Grant Five Additional Years
- Video From the Recent Humanity+ Conference
- Our Beautiful, Destructive Heritage of Myth
- Slicing Calorie Restriction Ever Finer
- Science Fictional Cancer Research

BISPHOSPHONATES GRANT FIVE ADDITIONAL YEARS

This is an unexpected result, arising from a human study of bisphosphonate treatment for osteoporosis, or age-related loss of bone mass and strength. Bisphosphonates are used to this end because they alter the balance of activity between cells that break down bone and cells that build bone:

https://www.fightaging.org/archives/2011/02/bisphosphonates-and-an-unusual-longevity.php

"Australian clinical researchers have noted an extraordinary and unexpected benefit of osteoporosis treatment - that people taking bisphosphonates are not only surviving well, better than people without osteoporosis, they appear to be gaining an extra five years of life. ... Out of a total cohort of around 2,000, a sub-group of 121 people were treated with bisphosphonates for an average of 3 years. When compared with other sub-groups taking other forms of treatment, such as Vitamin D (with or without calcium) or hormone therapy, the longer life associated with bisphosphonate treatment was marked and clear."

Much like rapamycin, another available treatment that might be expected to extend life in humans, bisphosphonate therapy is not something you'd want to undergo without reason to do so - there are a range of potentially serious side-effects. However, given the magnitude of this effect on human longevity, it seems worth further exploring the mechanisms of action now that it has landed in the lap of the research community.

VIDEO FROM THE RECENT HUMANITY+ CONFERENCE

L. Stephen Coles of the Gerontology Research Group and Gregory Benford, who is on the board of Genescient, spoke on the topics of aging and longevity science at the last Humanity+ conference. You'll find video and links to more from the conference in the following Fight Aging! post:

https://www.fightaging.org/archives/2011/01/is-there-a-maximum-human-life-span-and-longevity-for-the-long-term.php

OUR BEAUTIFUL, DESTRUCTIVE HERITAGE OF MYTH

Why is it that so many people are instinctively opposed to longevity science, the prospects for rejuvenating the old, and other plausible advances soon to be enabled by modern biotechnology?

https://www.fightaging.org/archives/2011/02/our-beauteous-but-destructive-heritage-of-myth-legend-and-stories.php

"Do people mistrust what their legends and tall tales tell them to be wary of, or does myth, ancient and modern, merely reflect a deeper set of human viewpoints? I suspect a little of both. ... We are headed towards the development of ways to defeat aging - and eliminate the consequent frailty and death by age-related disease - and yet so many people and so many myths welcome and romanticize aging and death.

"You may or may not be familiar with the Monomyth, but it should nonetheless be obvious that tales which reflect widely shared aspects of the human condition have a great and enduring power. Coming of age, attaining independence, romantic entanglements, challenge and adversity, victory over the odds - and an end to the tale in aging and death. We might say that every story is the story of the Fall: the golden past, the imperfect present, the uncertainty ahead. This is a mirror held to human lives as our millennia-long culture knows them: an age of health and triumph followed by a slow, knowing decline into the darkness we know nothing of. Aging and death are potent ingredients for authors, playwrights, and theologians, and were no less potent for the elders and shamans who came before them."

SLICING CALORIE RESTRICTION EVER FINER

Here, while trying to isolate the core processes of calorie restriction from its secondary effects, researchers find a biomarker that might be useful in measuring the prospects for all potential methods of slowing aging:

https://www.fightaging.org/archives/2011/02/slicing-calorie-restriction-ever-finer.php

"Over the past few years, researchers have designed and carried out interesting and ingenious experiments that try to narrow down which of the biological effects of calorie restriction are important when it comes to the resulting benefits to health and longevity. That calorie restriction notably lengthens healthy life span in almost all species tested to date is beyond doubt: eat less while still obtaining the necessary nutrients for survival and live longer as a consequence. The challenge for the scientific community is that the practice of calorie restriction changes an enormous range of metabolic processes and measures: levels of visceral fat tissue, expression patterns of genes known to be involved in aging, cell cycle behavior, body temperature, and so on down a long, long list. All of these factors are interdependent, and very hard to change in isolation of one another."

SCIENCE FICTIONAL CANCER RESEARCH

We already live in the future that our parents and grandparents could only read about:

https://www.fightaging.org/archives/2011/02/the-science-fictional-cancer-therapies-now-under-development.php

"If you grew up reading science fiction from the golden era of pulp and wide-eyed planetary optimism, then you've no doubt noticed that you are more or less already living in the shining future those authors wrote about. We ended up with computing power and biotechnology far beyond their imagining rather than near-free energy and space travel, but the results are just as impressive. On the whole we're better off with the direction taken by reality over fiction: massive low cost energy generation and distribution technologies wouldn't do anything to slow down the aging process.

"Following the latest cancer research news, I'm generally struck by just how much a lot of it sounds like the engineer-oriented science fiction inventions of yesteryear. For example, researchers can now place homing nanoparticles in the brain that destroy tumor tissue - and only tumor tissue - when heated by low-intensity radiation beams. Scientists can also also filter out metastatic cancer cells from the bloodstream using a range of techniques. Neither of these approaches would look out at all out of place in a Lensman novel. But nonetheless here we are."

DISCUSSION

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

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LATEST HEADLINES FROM FIGHT AGING!

STEM CELLS FROM FAT TO TREAT HEART DAMAGE
Friday, February 4, 2011
https://www.fightaging.org/archives/2011/02/stem-cells-from-fat-to-treat-heart-damage.php
From the MIT Technology Review: "Starting this month, a new European trial aims to determine whether stem cells harvested from a person's own fat, delivered shortly after a heart attack, could prevent some of the cardiac muscle damage that results from blocked arteries. During a heart attack, blood vessels that deliver blood to the heart muscle are blocked, and the lack of oxygen slowly kills the tissue. San Diego-based Cytori Therapeutics has developed a treatment that aims to prevent much of that muscle damage before it starts. It works by injecting a concentrated slurry of stem cells and other regenerative cells isolated from the patient's body directly into the heart's main artery within 24 hours after an attack. ... Time is muscle. The quicker you get in, the better. You can't do anything about dead tissue, but tissue that's bruised and damaged - that's revitalizable. If you can get new blood flow in there, that tissue comes back to life. ... fat tissue has its own population of stem cells that are more easily accessible and far more abundant than the ones in bone marrow. A typical sample of bone marrow yields about 5,000 stem cells; a sample of fat, gathered quickly through liposuction, can provide up to 200 times that amount. ... Fat tissue has been used for years by very astute surgeons, who just pulled pieces of fat into areas that weren't healing well. All the data so far has shown that these cells are safe, but beyond that, what are these cells doing? We just don't know. ... Cytori began a large-scale trial this month and hopes to test the procedure on 360 patients. The company aims to start large-scale clinical trials on heart attack patients in the United States by 2014 and on patients with chronic heart failure even earlier than that."

STEM CELLS AND SKIN CANCER
Friday, February 4, 2011
https://www.fightaging.org/archives/2011/02/stem-cells-and-skin-cancer.php
Via EurekAlert!: "A constellation of different stem cell populations within our skin help it to cope with normal wear and tear. By constantly proliferating, the stem cells allow skin to replenish itself, allowing each cell to be replaced by a new one about once a month. But the normal cycle of division and death within one or more of these stem cell types can sometimes be derailed by genetic mishaps. Such events are believed to spawn carcinomas and other deadly skin cancers ... [researchers] have now unmasked a long sought stem cell origin of carcinoma and identified the genetic lesions occurring within these cells that spur them on to malignancy. ... increased activity of a powerful oncogene called Ras combined with overly exuberant activity of a protein called ΔNp63α, stimulates the population of skin stem cells that produce keratin 15 - one of many keratin proteins found in the skin - promoting carcinoma development. ... When cells in the skin or anywhere else in the body sense a potentially cancer-causing threat such as an activated oncogene like Ras - which speeds up cell division - the cells cope by slamming on the brakes to trigger a process called senescence. This is a tumor-suppressive mechanism that halts cell division while allowing cells to stay metabolically active. ... Unfortunately there are a number of genetic events that can bypass senescence and push a cell down the road towards cancer."

PROGRESS IN BIOENGINEERED VEINS
Thursday, February 3, 2011
https://www.fightaging.org/archives/2011/02/progress-in-bioengineered-veins.php
From KurzweilAI.net: "New research [demonstrates] the capability of tissue-engineered vascular grafts that are immediately available at the time of surgery and are less likely to become infected or obstructed. A surgeon could pull a new human vein off the shelf for use in life-saving vascular surgeries.The bioengineering method of producing veins shows promise in large- and small-diameter applications, such as for coronary artery bypass surgery and for vascular access in hemodialysis. ... This new type of bioengineered vein allows them to be easily stored in hospitals so they are readily available to surgeons at the time of need. Currently, grafting using the patient's own veins remains the gold standard. But, harvesting a vein from the patient's leg can lead to complications, and for patients who don't have suitable veins, the bioengineered veins could serve as an important new way to provide a coronary bypass. ... In this research, scientists generated bioengineered veins in a bioreactor - a device designed to support a biological environment - and then stored them up to 12 months in refrigerated conditions. The bioengineered veins, 3 millimeters to 6 millimeters in diameter, demonstrated excellent blood flow and resistance to blockage in large animal models for up to a year. ... Not only are bioengineered veins available at the time of patient need, but the ability to generate a significant number of grafts from a cell bank will allow for a reduction in the final production costs, as compared to other regenerative medicine strategies. While there is still considerable research to be done before a product is available for widespread use, we are highly encouraged by the results outlined in this paper and eager to move forward with additional study."

AN EXAMPLE OF THE IMPORTANCE OF MITOCHONDRIAL DAMAGE
Thursday, February 3, 2011
https://www.fightaging.org/archives/2011/02/an-example-of-the-importance-of-mitochondrial-damage.php
Damage to our mitochondrial DNA is one of the root causes of aging, and here is a specific example of such damage associated with an age-related condition - all the more reason to aggressively fund repair strategies such as protofection and mitoSENS. From the paper: "Mitochondrial DNA damage may be associated with age-related diseases, such as age-related macular degeneration (AMD). The present study was designed to test whether the frequency of mitochondrial DNA (mtDNA) damage, heteroplasmic mtDNA mutations, and repair capacity correlates with progression of AMD. ... Macular and peripheral RPE cells were isolated and cultured from human donor eyes with and without AMD history. The stages of AMD were graded according to the Minnesota Grading System. ... To test the mtDNA repair capacity, cultured RPE cells were allowed to recover for 3 and 6 hours after exposure to H(2)O(2) and then repair assessed by quantitative PCR. The levels of human OGG1 protein, which is associated with mtDNA repair, were analyzed by Western Blot. ... Our study showed that mtDNA damage increased with aging, and more lesions occurred in RPE cells from the macular region relative to the periphery. Furthermore, mtDNA repair capacity decreased with aging, with less mtDNA repair capacity in the macular region compared with the periphery in samples from aged subjects. Most interestingly, the mtDNA damage is positively correlated with the grading level of AMD, while repair capacity is negatively correlated. In addition, more mitochondrial heteroplasmic mutations were detected in eyes with AMD. ... Our data show macula-specific increases in mtDNA damage, heteroplasmic mutations and diminished repair that are associated with aging and AMD severity."

SENS FOUNDATION ON IMMUNE SYSTEM REJUVENATION
Wednesday, February 2, 2011
https://www.fightaging.org/archives/2011/02/sens-foundation-on-immune-system-rejuvenation.php
From the SENS Foundation: "The degenerative aging of the immune system is responsible for an enormous burden of disease and disability, from the pain of recurrent Herpes zoster and postherpetic neuralgia, to elevated rates of chronic urinary tract infections, to complications in wounds, pressure sores, ulcers, and surgical incisions. Most prominently, it underlies the meteoric rise in mortality from respiratory infections with age: influenza, pneumonia, and septicemia rise from being negligible causes of death in healthy middle-aged adults in the USA, to emerge amongst the top 10 causes of death in adults over the age of 55, with mortality rates climbing with each successive year of aging. And in addition to increasing the morbidity and mortality specifically attributable to particular infections, the dysregulation of immune function by immunosenescence is widely acknowledged to exacerbate multiple chronic age-related illnesses, and to contribute to functional decline and frailty in aging people. While vaccine manufacturers and public health officials have rightly advocated for expansion of population vaccine coverage as a measure to blunt the burden of infectious disease in the elderly, the effectiveness of this strategy is itself limited by immunosenescence, which progressively diminishes the adaptive immune system's response to vaccination with age ... The solution to age-related suffering and death from specific infections, autoimmunity, and inflammation is the application of rejuvenation biotechnology to the aging immune system itself. The clearest and longest-established contributor to immune senescence is the decline in adaptive immunity mediated by T lymphocytes, the biomedical remediation of which has therefore been the focus of SENS Foundation's investments in immunological rejuvenation research."

AGES AND ALZHEIMER'S DISEASE
Wednesday, February 2, 2011
https://www.fightaging.org/archives/2011/02/ages-and-alzheimers-disease.php
It can be argued that advanced glycation endproducts play an important role in Alzheimer's disease, as well as other degenerations of aging. Here is a review paper on the topic: "Alzheimer's disease (AD) is the most common dementia disorder of later life. Although there might be various different triggering events in the early stages of the disease, they appear to converge on a few characteristic final pathways in the late stages, characterized by inflammation and neurodegeneration. Here, we review the hypothesis that advanced glycation end products (AGEs), which reflect carbonyl stress, an imbalance between the production of reactive carbonyl compounds and their detoxification, can serve as biomarkers for the progression of disorder. AGE modification may explain many of the neuropathological and biochemical features of AD, such as extensive protein cross-linking shown as amyloid plaques and neurofibrillary tangles, inflammation, oxidative stress and neuronal cell death. Although accumulation of AGEs is a normal feature of aging, it appears to be significantly accelerated in AD. We suggest that higher AGE concentrations in brain tissue and in cerebrospinal fluid might be able to distinguish between normal aging and AD." Effective removal of AGEs through strategies such as bioremediation is one part of the SENS research agenda.

THOUGHTS ON MACROMOLECULAR DAMAGE AND HUMAN LIFE SPAN
Tuesday, February 1, 2011
https://www.fightaging.org/archives/2011/02/thoughts-on-macromolecular-damage-and-human-life-span.php
Macromolecules are parts in our cellular machinery, themselves large and complex arrangements of atoms. Some of these macromolecules are short lived and rapidly recycled, but many are not. They are vulnerable to damage in ways that can significantly alter their behavior - such as by reacting with free radicals generated by mitochondria, or being glued together into advanced glycation end-products. Here is a paper offering some thoughts on what that means for human aging: "A number of tissues and organs in the human body contain abundant proteins that are long-lived. This includes the heart, lung, brain, bone and connective tissues. It is proposed that the accumulation of modifications to such long-lived proteins over a period of decades alters the properties of the organs and tissues in which they reside. Such insidious processes may affect human health, fitness and ultimately may limit our lifespan. The human lens, which contains proteins that do not turnover, is used to illustrate the impact of these gradual deleterious modifications. On the basis of data derived from the lens, it is postulated that the intrinsic instability of certain amino acid residues, which leads to truncation, racemisation and deamidation, is primarily responsible for the age-related deterioration of such proteins. Since these post-translational modifications accumulate over a period of many years, they can only be studied using organisms that have lifespans measured in decades. One conclusion is that there may be important aspects of human aging that can be studied only using long-lived animals." With or without further study, researchers know that these forms of damage exist and know how best to proceed to fix them - it's just a matter of funding and the will to proceed.

EXERCISE IMPROVES MEMORY AND BRAIN HEALTH
Tuesday, February 1, 2011
https://www.fightaging.org/archives/2011/02/exercise-improves-memory-and-brain-health.php
Yet another reason to keep up with your exercise routine: "A new study shows that one year of moderate physical exercise can increase the size of the brain's hippocampus in older adults, leading to an improvement in spatial memory. [This] is considered the first study of its kind focusing on older adults who are already experiencing atrophy of the hippocampus, the brain structure involved in all forms of memory formation. ... The scientists recruited 120 sedentary older people without dementia and randomly placed them in one of two groups - those who began an exercise regimen of walking around a track for 40 minutes a day, three days a week, or those limited to stretching and toning exercises. Magnetic resonance images were collected before the intervention, after six months, and at the end of the one-year study. The aerobic exercise group demonstrated an increase in volume of the left and right hippocampus of 2.12 percent and 1.97 percent, respectively. The same regions of the brain in those who did stretching exercises decreased in volume by 1.40 and 1.43 percent, respectively. Spatial memory tests were conducted for all participants at the three intervals. Those in the aerobic exercise group showed improved memory function, when measured against their performance at the start of the study, an improvement associated with the increased size of the hippocampus. The authors also examined several biomarkers associated with brain health, including brain-derived neurotrophic factor (BDNF), a small molecule that is involved in learning and memory. They found that the increases in hippocampal size were associated with increased amounts of BDNF. ... We think of the atrophy of the hippocampus in later life as almost inevitable. But we've shown that even moderate exercise for one year can increase the size of that structure. The brain at that stage remains modifiable."

THE PROSPECTS FOR KIDNEY STEM CELL THERAPIES
Monday, January 31, 2011
https://www.fightaging.org/archives/2011/01/the-prospects-for-kidney-stem-cell-therapies.php
From the Harvard Gazette: "It has long been a given that adult humans - and mammals in general - lack the capacity to grow new nephrons, the kidney's delicate blood filtering tubules, which has meant that dialysis, and ultimately kidney transplantation, is the only option for the more than 450,000 Americans who have kidney failure. But a new study [may] turn that paradigm on its head, and someday lead to a new treatment for those suffering from kidney disease. ... [researchers have] identified adult kidney stem cells in the zebrafish that can generate new nephrons. These cells can be transplanted from one fish to another fish, whereby they grow into functional nephrons in the transplanted recipient. [This] provides a proof of principle that adult kidney stem cells exist in nature and that treating renal disease with a stem cell-type therapy is theoretically possible. ... Investigators have been searching for the adult renal stem cell in mice and humans for some time, but so far the results have been controversial. ... There is a general belief that while there are kidney stem cells in mammals, including humans, they generate nephrons and then disappear during fetal development or soon after birth. ... The mystery is why these particular cells aren't retained in the adult kidney, where they could be called upon to make new nephrons."

SKIN CELLS DIRECTLY CONVERTED TO BEATING HEART CELLS
Monday, January 31, 2011
https://www.fightaging.org/archives/2011/01/skin-cells-directly-converted-to-beating-heart-cells.php
From ScienceDaily: "scientists have converted adult skin cells directly into beating heart cells efficiently without having to first go through the laborious process of generating embryonic-like stem cells. The powerful general technology platform could lead to new treatments for a range of diseases and injuries involving cell loss or damage, such as heart disease, Parkinson's, and Alzheimer's disease. ... this work represents a new paradigm in stem cell reprogramming. We hope it helps overcome major safety and other technical hurdles currently associated with some types of stem cell therapies. ... scientists have been trying to develop ways to 'reprogram' adult human cells back to a more embryonic-like, or pluripotent, state, from which they are able to divide and then change into any of the body's cell types. ... Although the technology to generate these cells, dubbed induced pluripotent stem (iPS) cells, represents a major advance, there are some hurdles to overcome before it can be adapted to therapies. ... [researchers] decided to try to tweak the process by completely bypassing the iPS stage and going directly from one type of mature cell (a skin cell) to another (a heart cell). ... the protocol is fundamentally different from what has been done by other scientists in the past [and] giving the cells a different kind of signal could turn them into brain cells or pancreatic cells."
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