Fight Aging! Newsletter, August 15th 2011

August 15th 2011

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!



- Nobody is Arguing that Radical Life Extension is Impossible
- The Promise of Advanced Immune Therapies
- Another Important Muscle Structure Built in the Lab
- Long-Term Data on the Consequences of Excess Fat
- Discussion
- Latest Headlines from Fight Aging!


A thought for the day:

"Nobody out there is seriously arguing for the impossibility of radical life extension, and I don't think anyone has been for quite some time. It is a given in the present diffuse discussion on the future of medicine and human longevity that at some point advances in biotechnology and nanotechnology will lead to greatly extended lives: centuries and longer lived in good health and vigor. Aging will be brought under control by medicine, like any number of other once intractable medical conditions.

"It wasn't always this way. People in past centuries might have hoped for the plausibility of radical life extension, but couldn't have said in certainty that it was possible. We, on the other hand, know far more about physics, chemistry, and biology: we know that there is no wall created by the way the universe works standing in our way. The only reason we presently age and suffer is because we haven't yet advanced far enough down the path of biotechnology that is clearly visible and well understood. Aging is, at root, a matter of atoms and molecules in the wrong place and the wrong configuration. Moving atoms and molecules around to order, en masse, and with precision, is a task that we know is possible. We do it all the time, and are learning ever greater finesse with each passing decade.

"Yesterday the tools were found molecules that happened to do something useful with other molecules. Today we make use of designed molecules for particular operations, knowing much more about the molecular machinery of our cells. Tomorrow the biotechnologists will build and repair complex molecular machinery that performs far more effectively than our evolved biology. Thus discussions on the engineering of human longevity focus on how, when, and (sadly) whether it should be done at all."


A good example as to why manipulating the immune system is a very promising line of technology surfaced this past week:

"The immune system is a powerful tool for the selective destruction of unwanted cells, and researchers are a fair way down the road of engineering the activity of the immune system to form therapies. ... In the research published Wednesday, doctors at the University of Pennsylvania say the treatment made the most common type of leukemia completely disappear in two of the patients and reduced it by 70 percent in the third. In each of the patients as much as five pounds of cancerous tissue completely melted away in a few weeks, and a year later it is still gone."


The tissue engineering community is advancing by leaps and bounds these days:

"Recreating structured muscle is the simple stuff on a relative scale of difficulty - at least in comparison to lungs and other intricate organs - but this is still a very challenging task. Dumb muscle isn't just dumb muscle: it has to be the right shape, have the right nerve structures, the right distribution of tiny blood vessels, the right layering and fiber types, and so forth. Don't underestimate just how much work was involved in coming to the point at which researchers can announce [that they] have built the first functional anal sphincters in the laboratory, suggesting a potential future treatment for both fecal and urinary incontinence. Made from muscle and nerve cells, the sphincters developed a blood supply and maintained function when implanted in mice. ... this is one of the areas where the available prosthetic alternatives are just not that great; engineering a replacement sphincter in machinery is a hard challenge at our present level of technological prowess. So that a research team has constructed a functional biological sphincter is very promising - and this is especially true given that there are dozens of sphincters scattered throughout the body. It is an oft-reused structure, and being able to build any one type of sphincter from a patient's own cells implies that building the others is also a very realistic goal. So all in all, this is an encouraging example of progress in the field."


"Don't get fat and don't stay fat" seems to be generally good advance at any age at this point, given the data to hand. The lifestyle choices required to become fat - eating a lot, exercising too little - appear corrosive to long term health.

"The data on what exactly excess body fat will do to you - on average, statistically speaking - has been growing over the past years. Fat is metabolically active, an eager and pushy partner in the feedback loops and controlling systems of your metabolism. A lot of what it does is bad in the long term: spurring chronic inflammation, for example. Even comparatively early in life, putting on the pounds and keeping them on for years at a time has a sizable impact on your risk of later suffering all of the most common age-related conditions. Failing to exercise appears to be just as bad in a whole different set of ways.

"Research from Adventist Health Studies recently published in the Journal of the American Geriatrics Society showed that men over 75 with a body mass index (BMI) greater than 22.3 had a 3.7-year shorter life expectancy, and women over 75 with a BMI greater than 27.4 had a 2.1-year shorter life expectancy. .... We had a unique opportunity to do 29 years of follow-up with a cohort that was also followed for mortality outcomes. Across this long period of time, we had multiple measures of body weight, which provided a more accurate assessment."


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, August 12, 2011
Damage to mitochondrial membranes is an important feature of the complex process by which mitochondrial DNA damage contributes to aging. It is known that differences in membrane composition may be an important factor in species of unusual longevity, such as naked mole rats. Here is another open access study on this topic: "The cellular energy produced by mitochondria is a fundamental currency of life. However, the extent to which mitochondrial (mt) performance (power and endurance) is adapted to habitats and life-strategies of vertebrates is not well-understood. A global analysis of mt genomes revealed that hydrophobicity (HYD) of mt membrane proteins (MMPs) is much lower in terrestrial vertebrates than in fishes and shows a strong negative correlation with serine/threonine composition (STC). Here, we present evidence that this systematic feature of MMPs was crucial for the evolution of large terrestrial vertebrates with high aerobic capacity. An Arrhenius-type equation gave positive correlations between STC and maximum lifespan (MLS) in terrestrial vertebrates ... In particular, marked STC-increases in primates (especially hominoids) among placentals were associated with very high MLS-values. We connected these STC-increases in MMPs with greater stability of respiratory complexes." This sort of study should be viewed as supporting evidence for the importance of work on repairing mitochondrial damage - confirmation of the importance of mitochondria to aging and longevity.

Friday, August 12, 2011
Uncoupling proteins are involved in the processes by which metabolism determines natural longevity through their effects on mitochondrial activity, and are of interest to calorie restriction researchers: "The brown fat specific UnCoupling Protein 1 (UCP1) is involved in thermogenesis, a process by which energy is dissipated as heat in response to cold stress and excess of caloric intake. Thermogenesis has potential implications for body mass control and cellular fat metabolism. In fact, in humans, the variability of the UCP1 gene is associated with obesity, fat gain and metabolism. Since regulation of metabolism is one of the key-pathways in lifespan extension, we tested the possible effects of UCP1 variability on survival. Two polymorphisms (A-3826G and C-3740A), falling in the upstream promoter region of UCP1, were analyzed in a sample of 910 subjects from southern Italy (475 women and 435 men; age range 40-109). By analyzing haplotype specific survival functions we found that the A-C haplotype favors survival in the elderly. Consistently, transfection experiments showed that the luciferase activity of the construct containing the A-C haplotype was significantly higher than that containing the G-A haplotype. Interestingly, the different UCP1 haplotypes responded differently to hormonal stimuli. The results we present suggest a correlation between the activity of UCP1 and human survival, indicating once again the intricacy of mechanisms involved in energy production, storage and consumption as the key to understanding human aging and longevity."

Thursday, August 11, 2011
A novel way to manipulate stem cells: "Though the heart is known to contain some stem cells, they have a very limited ability to repair damage caused by a heart attack [and] researchers have had to look elsewhere. One of the first efforts to use stem cells to reduce heart scarring involved harvesting them from the bone marrow and inserting them back into the heart muscle, close to the heart's blood supply, but this had limited success. Prof. Oron, who has long used low level lasers to stimulate stem cells to encourage cell survival and the formation of blood vessels after a heart attack, was inspired to test how laser treatments could also work to heal the heart. He and his fellow researchers tried different methods, including treating the heart directly with low level lasers during surgery, and 'shining' harvested stem cells before injecting them back into the body. But he was determined to find a simpler method. After a low-level laser was 'shined' into a person's bone marrow - an area rich in stem cells - the stem cells took to the blood stream, moving through the body and responding to the heart's signals of distress and harm ... Once in the heart, the stem cells used their healing qualities to reduce scarring and stimulate the growth of new arteries, leading to a healthier blood flow. To determine the success of this method, Prof. Oron performed the therapy on an animal model. Following the flow of bone marrow stem cells through the use of a fluorescent marker, the researchers saw an increase in stem cell population within the heart, specifically in the injured regions of the heart. The test group that received the shining treatment showed a vastly higher concentration of cells in the injured organ than those who had not been treated with the lasers."

Thursday, August 11, 2011
The I'm Not Dead Yet (INDY) gene is one of the earlier longevity genes discovered by researchers in course of investigating the effects of calorie restriction. Here is a recent update: "It is known that excess calorie consumption leads to obesity, insulin resistance and increased mortality, whereas calorie restriction reduces accumulation of body fat and improves cellular energy balance and insulin action - reversing obesity and type 2 diabetes, delaying the aging process, and prolonging life in primates and many other species. It has also been shown in the past that reduced expression of the so-called 'INDY' gene in D. Melanogaster flies and C. elegans worms promotes longevity in a manner similar to calorie restriction. But until now, the cellular mechanism by which this happens was unknown. [Researchers] generated a mouse with the so-called 'INDY' gene deleted. Loss of the gene altered chemical levels in the cellular signaling network in a way that improved mitochondrial action in the liver, metabolism of fatty acids, and cellular energy transport. Overall, these traits protected the mice from diet-related accumulation of body fat and insulin resistance that evolve, as we age, into type 2 diabetes. Discovering how deletion of the INDY gene would impact mitochondrial metabolism in the liver was key, because that is the main organ where the INDY gene does its work."

Wednesday, August 10, 2011
Why are hearts in humans and other higher animals not able to regenerate like salamander hearts? Answering that question would be a step on the road to recreating that ability when needed: "A new study has shed light on why adult human cardiac cells lose their ability to proliferate, perhaps explaining why our heart have little regenerative capacity. The study, done in cell lines and mice, may lead to methods of reprogramming a patient's own cardiac myocytes, or muscle cells, within the heart itself to create new muscle to repair damage ... Recent research suggests that mammals do have the ability to regenerate the heart for a very brief period, about the first week of life. ... During human development, cardiac myocytes are made by progenitor stem cells and proliferate to form the heart. Once the heart is formed, the myocytes transform from immature cells into mature cells that cannot proliferate. That's not so for newts and salamanders, whose cardiac myocytes can go back and forth between immature, or primitive, states to proliferate and repair damage and then revert back into mature cells once the damage is repaired. [Researchers believe] the reason adult human cardiac myocytes can't do this is quite simple - when the myocytes are in a more primitive state, they are not as good at contracting, which is vital for proper heart function. Because humans are much larger than newts and salamanders, we needed more heart contraction to maintain optimum blood pressure and circulation."

Wednesday, August 10, 2011
Another of the many benefits of exercise: a study "shows that a small amount of physical exercise could profoundly protect the elderly from long-term memory loss that can happen suddenly following infection, illnesses or injury in old age. ... aging rats that ran just over half a kilometer each week were protected against infection-induced memory loss. ... Our research shows that a small amount of physical exercise by late middle-aged rats profoundly protects against exaggerated inflammation in the brain and long-lasting memory impairments that follow a serious bacterial infection. Strikingly, this small amount of running was sufficient to confer robust benefits for those that ran over those that did not run. This is an important finding because those of advanced age are more vulnerable to memory impairments following immune challenges such as bacterial infections or surgery. With baby boomers currently at retirement age, the risk of diminished memory function in this population is of great concern. Thus, effective noninvasive therapies are of substantial clinical value. ... Past research has shown that exercise in humans protects against declines in cognitive function associated with aging and protects against dementia. Researchers also have shown that dementia is often preceded by bacterial infections, such as pneumonia, or other immune challenges. ... Previous research has shown that immune cells of the brain, called microglia, become more reactive with age. When the older rats in the study encountered a bacterial infection, these immune cells released inflammatory molecules called cytokines in an exaggerated and prolonged manner. ... In the current study we found that small amounts of voluntary exercise prevented the priming of microglia, the exaggerated inflammation in the brain, and the decrease of growth factors."

Tuesday, August 9, 2011
An interesting open access paper describes one of many approaches to building skin from a scaffold material and a patient's own cells: "The ideal biomaterial should promote attachment, proliferation and growth of cells. Additionally, it should degrade in an appropriate time period without releasing harmful substances, but not exert a pathological immune response. Spider dragline silk from Nephila spp meets these demands to a large extent. ... Native spider dragline silk, harvested directly out of Nephila spp spiders, was woven on steel frames. Constructs were sterilized and seeded with fibroblasts. After two weeks of cultivating single fibroblasts, keratinocytes were added to generate a bilayered skin model, consisting of dermis and epidermis equivalents. ... Both fibroblasts and keratinocytes cell lines adhere to the spider silk fibres and proliferate. Guided by the spider silk fibres, they sprout into the meshes and reach confluence in at most one week. A well-balanced, bilayered cocultivation in two continuously separated strata can be achieved by serum reduction, changing the medium conditions and the cultivation period at the air/liquid interphase. Therefore spider silk appears to be a promising biomaterial for the enhancement of skin regeneration."

Tuesday, August 9, 2011
The aging immune system is misconfigured, overpopulated by too many of the wrong sorts of immune cell, while having too few useful cells left to perform the important jobs - such as resisting infections, attacking cancers, and removing senescent cells, for example. One approach to dealing with this problem is to destroy the unwanted cells, and there's evidence for at least some parts of the immune system to show that this is beneficial. Another approach is to use biotechnology to expand the population of useful cells, and this recent release fits into that line of work: "Aging brings about a selective decline in the numbers and function of T cells - a type of white blood cell involved in the immune system's response to infection - and T cells that survive the longest may better protect against infections such as the flu ... The finding may lead to targeting these cells with vaccinations that increase their number and improve protection against disease in older adults. ... The decline in immune function with age is viewed as the most important contributing factor to older adults' increased susceptibility to infections and decreased responses to vaccinations. ... We have discovered that aging brings about selective attrition of those T cells that defend us against new infections that we have not encountered before. Not all T cells age the same and the ones that will survive the longest have special features. ... Finding ways to expand them is our next and final challenge, and our team [should] be able to achieve that in the next few years."

Monday, August 8, 2011
From the SENS Foundation, a look at what might be done to remove damaging cellular aggregates, such as the amyloid beta (Aβ) implicated in Alzheimer's disease (AD), by manipulating the function of lysosomes, the cellular recycling machinery: "Dr. Ben Bahr and his colleagues with the Neurosciences Program and Division of Pharmaceutical Sciences at the University of Connecticut have for some time now been investigating the effects of elevating lysosomal activity using the lysosomal modulator Z-Phe-Ala-diazomethylketone (PADK). ... In a new study, Dr. Bahr's group has extended this work into a transgenic mouse model of AD, testing PADK's ability to retard, and to reverse, AD neuropathology and cognitive dysfunction in two models of transgenic AD mice ... . Systemic PADK injection of PADK in both models caused 3- to 8-fold increases in cathepsin B levels and similar elevations in the enzyme's activity in lysosomal cell fractions ... Accordingly PADK-induced lysosomal modulations cleared a significant amount of the intra- and extraneuronal burden of Aβ from treated mice, reducing intraneuronal Aβ regions of the hippocampus and piriform cortex by 63 - 73% in younger mice and by ~50% in older ones ... As expected, model AD mice also exhibited substantial impairment of performance on cognitive-behavioral tests including the suspended rod, exploratory habituation, and spontaneous alternation behavior in a T-maze tests. PADK-induced Aβ clearance resulted in the complete restoration of normal function in both young and old animals. ... As a tribute to the power of the cellular waste-disposal machinery, these results are impressive. Equally, they are not a solution to human brain aging. These animals, like most transgenic models of AD, exhibit no tau pathology nor significant neuronal loss - problems that will also have to be addressed in order to achieve the full prevention of AD and rejuvenation of aging brains."

Monday, August 8, 2011
As noted in the past here at Fight Aging!, the weight of evidence suggests that presently available antioxidant supplements either do nothing or somewhat harm long term health - the fervor for them is nothing more than magical thinking based on the effects antioxidants can have on cells in culture, and on the beneficial effects of mitochondrially targeted antioxidant compounds. That, however, is a long way removed from what you eat and what happens in a complex system like a living animal. Fortunately, sense is slowly starting to emerge in the media: "Few medical remedies have a more sterling reputation than that assortment of foods, pills, and general life maneuvers known collectively as 'antioxidants.' At last, here's something that promises better heart health, improved immunity, a pellucid complexion as well as relief against cancer, arthritis, and the blahs - and it's all-natural! What's not to like? Well, there is a wee small problem in our ongoing anti-oxidize-athon: As it turns out, we have no evidence that antioxidants are beneficial in humans. ... In fact [the] best available data demonstrate that antioxidants are bad for you - so long as you count an increased risk of death as 'bad.' ... But, hey, who ever let a little evidence stand in the way of a good time? Especially in this case, when the charge toward lifestyle legitimacy has been led by willowy celebrities with karmic equipoise."



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