Fight Aging! Newsletter, December 5th 2011

December 5th 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!



- Regenerating Mouse Muscle
- An Example of Cancer Immunotherapy
- Cautionary Data on IGF-1 and Longevity
- Discussion
- Latest Headlines from Fight Aging!


Here is news of an approach in muscle regeneration that shows some promise:

"Spurring regeneration of muscle is of interest as as a part of any future rejuvenation biotechnology package because humans and other mammals progressively lose muscle mass and strength with age - aside from the sedentary lifestyle that most older people adopt, there are underlying processes that sap muscle strength even in athletes. Stepping on the gas and telling the body to build new muscle - when it ordinarily would not do so - isn't as good an approach as preventing muscle loss from happening in the first place, or at least attenuating some of the mechanisms involved, but it certainly closer to realization at this point in time.

"Researchers removed a portion of the tibialis anterior leg muscle in several mice (the muscle was chosen because injury to it affects the foot's range of motion but doesn't prevent the mice from walking). In some mice, the injuries were left to heal on their own. In others, the wound was filled with bundles of microthreads seeded with reprogrammed human muscle cells. The untreated mice developed significant scarring at the injury site, with no restoration of muscle function. In sharp contrast, the mice that received the reprogrammed cells grew new muscle fibers and developed very little scarring.
Tests done 10 weeks after implantation showed that the regenerated tibialis anterior muscle functioned with nearly as much strength as an uninjured muscle."


In recent years researchers have demonstrated many different ways to turn a patient's immune system into a targeted cancer killing device, and here is another:

"Researchers from UCLA's cancer and stem cell centers have demonstrated for the first time that blood stem cells can be engineered to create cancer-killing T-cells that seek out and attack a human melanoma. ... Researchers used a T-cell receptor from a cancer patient cloned by other scientists that seeks out an antigen expressed by this type of melanoma. They then genetically engineered the human blood stem cells by importing genes for the T-cell receptor into the stem cell nucleus using a viral vehicle. The genes integrate with the cell DNA and are permanently incorporated into the blood stem cells, theoretically enabling them to produce melanoma-fighting cells indefinitely and when needed.

"In the study, the engineered blood stem cells were placed into human thymus tissue that had been implanted in the mice, allowing Zack and his team to study the human immune system reaction to melanoma in a living organism. Over time, about six weeks, the engineered blood stem cells developed into a large population of mature, melanoma-specific T-cells that were able to target the right cancer cells. ... The study included nine mice. In four animals, the antigen-expressing melanomas were completely eliminated. In the other five mice, the antigen-expressing melanomas decreased in size."


One of the consequences of the complexity of metabolism and its relationship to longevity is that conclusions based on research are more prone to being overturned on closer inspection:

"Metabolism is complex - very, very complex. In areas that have been well studied for more than a decade, researchers are still pushing back and forth on whether well known genes and pathways are actually important in longevity. In this sort of environment a single study in a few dozen mice isn't worth much, as the results from these various studies are either are all over the map, or prone to being overturned by a more careful, well-funded, and larger research project. That is what seems to have happened here for IGF-1 and longevity.

"One of the major discoveries in aging during the past decade has been the observation that mutations in insulin/IGF-1 signaling led to increased longevity in various invertebrate models. [There have been studies showing that this effect is present in mammals such as mice, but our more rigorous] data show [that] reduced IGF-1R signaling in mammals does not play the same major role in aging that is observed in invertebrates."


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 2, 2011
From In Search of Enlightenment: "Looking back over our species' history, as told in fossil records, what do we find? ... Prehistoric human remains have never revealed individuals older than about 50 years of age, and humans had a life expectancy at birth of 30 years or less for more than 99.9% of the time that we have inhabited this planet. ... So for most of our species' history there was little progress in terms of increasing life expectancy at birth. But things began to change in the 19th century. Advances in technology (e.g. the sanitation revolution), medical knowledge, material resources and changes in behaviour helped change the future course of our species. ... The fossil records of the 21st century will be unique in our species' history for two reasons. Firstly, there will be more human remains this century than in any other century (because of the size of the human population). Furthermore, the vast majority of these deaths will be caused by chronic disease and will afflict people after the age of 60. Isn't it odd, given how many people are projected to suffer and die from chronic disease and given the rapid progress that is being made in the biomedical sciences, that we don't invest more of our energies into tackling the leading cause of chronic disease? Namely, aging. When future generations look back at the 21st century they will wonder why we didn't act sooner to try to ameliorate the high risks of morbidity and mortality that currently ravage our bodies and minds."

Friday, December 2, 2011
Here is another study showing that rapamycin can extend life in mammals: "The nutrient-sensing TOR (target of rapamycin) pathway is involved in cellular and organismal aging. Rapamycin, an inhibitor of TOR, extends lifespan in yeast, fruit flies and genetically heterogeneous mice. Here, we demonstrate that lifelong administration of rapamycin extends lifespan in female 129/Sv mice characterized by normal mean lifespan of [two years]. Importantly, rapamycin was administrated intermittently (2 weeks per month) starting from the age of [two months]. Rapamycin inhibited age-related weight gain, decreased aging rate, increased lifespan (especially in the last survivors) and delayed spontaneous cancer. 22.9% of rapamycin-treated mice survived the age of death of the last mouse in control group. Thus we demonstrated for the first time in normal inbred mice that lifespan can be extended by rapamycin. This opens an avenue to develop optimal doses and schedules of rapamycin as an anti-aging modality."

Thursday, December 1, 2011
Mitochondria are the power plants of the cell, the evolved remnants of what were originally symbiotic bacteria, and which still possess their own fragile DNA distinct from that in the cell nucleus. They churn away producing the adenosine_triphosphate (ATP) used as an energy source in cellular processes, and are clearly of great importance in determining longevity. Scientists have for some years been carefully pulling apart the core mitochondrial machinery to better understand why this is the case, and here is an example of this ongoing research: "A decrease in mitochondrial electron transport chain (ETC) activity results in an extended lifespan in Caenorhabditis elegans. This longevity has only been reported when complexes I, III and IV genes are silenced, but not genes of complex II. We now have suppressed each complex II subunit in turn and have confirmed that in no case is lifespan extended. Animals with impaired complex II function exhibit similar metabolic changes to those observed following suppression of complexes I, III and IV genes, but the magnitude of the changes is smaller. Furthermore, an inverse correlation exists between mitochondrial membrane potential and ATP levels, which strongly suggests that dynamic allocation of energy resources is maintained. In contrast, suppression of genes from complexes I, III and IV, results in a metabolic crisis with an associated stress response and loss of metabolic flexibility. Thus, the maintenance of a normal metabolism at a moderately decreased level does not alter normal lifespan, whereas metabolic crisis and induction of a stress response is linked to lifespan extension."

Thursday, December 1, 2011
As a follow up to an earlier post on why DNA sequencing is of interest to those of us who follow longevity science, here is a look at the present state of the sequencing industry: "BGI, based in China, is the world's largest genomics research institute, with 167 DNA sequencers producing the equivalent of 2,000 human genomes a day. BGI churns out so much data that it often cannot transmit its results to clients or collaborators over the Internet or other communications lines because that would take weeks. Instead, it sends computer disks containing the data, via FedEx. ... the ability to determine DNA sequences is starting to outrun the ability of researchers to store, transmit and especially to analyze the data. ... Data handling is now the bottleneck. It costs more to analyze a genome than to sequence a genome. ... That could delay the day when DNA sequencing is routinely used in medicine. In only a year or two, the cost of determining a person's complete DNA blueprint is expected to fall below $1,000. But that long-awaited threshold excludes the cost of making sense of that data, which is becoming a bigger part of the total cost as sequencing costs themselves decline. ... We believe the field of bioinformatics for genetic analysis will be one of the biggest areas of disruptive innovation in life science tools over the next few years."

Wednesday, November 30, 2011
The use of 3D printers is spreading in medical research and development: "researchers have used a 3D printer to create a bone-like material and structure that can be used in orthopedic procedures, dental work, and to deliver medicine for treating osteoporosis. Paired with actual bone, it acts as a scaffold for new bone to grow on and ultimately dissolves with no apparent ill effects. The authors [say] they're already seeing promising results with in vivo tests on rats and rabbits. It's possible that doctors will be able to custom order replacement bone tissue in a few years ... If a doctor has a CT scan of a defect, we can convert it to a CAD file and make the scaffold according to the defect ... The material grows out of a four-year interdisciplinary effort involving chemistry, materials science, biology and manufacturing. A main finding of the paper is that the addition of silicon and zinc more than doubled the strength of the main material, calcium phosphate. The researchers also spent a year optimizing a commercially available ProMetal 3D printer designed to make metal objects. The printer works by having an inkjet spray a plastic binder over a bed of powder in layers of 20 microns, about half the width of a human hair. Following a computer's directions, it creates a channeled cylinder the size of a pencil eraser. After just a week in a medium with immature human bone cells, the scaffold was supporting a network of new bone cells."

Wednesday, November 30, 2011
Via EurekAlert!: "One of the earliest known impairments caused by Alzheimer's disease - loss of sense of smell - can be restored by removing a plaque-forming protein in a mouse model of the disease. The study confirms that the protein, called amyloid beta, causes the loss. ... The evidence indicates we can use the sense of smell to determine if someone may get Alzheimer's disease, and use changes in sense of smell to begin treatments, instead of waiting until someone has issues learning and remembering. We can also use smell to see if therapies are working. ... just a tiny amount of amyloid beta - too little to be seen on today's brain scans - causes smell loss in mouse models. Amyloid beta plaque accumulated first in parts of the brain associated with smell, well before accumulating in areas associated with cognition and coordination. Early on, the olfactory bulb, where odor information from the nose is processed, became hyperactive. Over time, however, the level of amyloid beta increased in the olfactory bulb and the bulb became hypoactive. Despite spending more time sniffing, the mice failed to remember smells and became incapable of telling the difference between odors. The same pattern is seen in people with the disease. They become unresponsive to smells as they age. ... The team then sought to reverse the effects. Mice were given a synthetic liver x-receptor agonist, a drug that clears amyloid beta from the brain. After two weeks on the drug, the mice could process smells normally. After withdrawal of the drug for one week, impairments returned."

Tuesday, November 29, 2011
Via ScienceDaily: "researchers studied hematopoietic stem cells, which create the cells that comprise the blood and immune system. Understanding when and how these stem cells begin to falter as the years pass may explain why some diseases, such as acute myeloid leukemia, increase in prevalence with age, and also why elderly people tend to be more vulnerable to infections such as colds and the flu. ... We know that immune system function seems to decline with increasing age. This is the first study comparing the function and gene expression profiles of young and old purified, human hematopoietic stem cells, and it tells us that these clinical changes can be traced back to stem cell function. ... Specifically, the researchers found that hematopoietic stem cells from healthy people over age 65 make fewer lymphocytes - cells responsible for mounting an immune response to viruses and bacteria - than stem cells from healthy people between ages 20 and 35. (The cells were isolated from bone marrow samples.) Instead, elderly hematopoietic stem cells, or HSCs, have a tendency to be biased in their production of another type of white blood cell called a myeloid cell. This bias may explain why older people are more likely than younger people to develop myeloid malignancies."

Tuesday, November 29, 2011
A commentary from the SENS Foundation: "Rejuvenation biotechnology encompasses a suite of advanced medical therapies, each of which removes, repairs, replaces, or renders harmless one of the forms of cellular or molecular damage that accumulates in an aging tissue over time and impairs its function. Through the comprehensive abatement of all such aging damage to levels approximating those of younger adults, tissue structure and function can be made more youthful, restoring the health and vigor of aging persons to that of persons years or decades younger. This approach is most prominently under pursuit in the development of cell therapy and tissue engineering, of which the most striking success to date has been the use of fetal and embryonic mesencephalic tissue grafts to replace dopaminergic (DA) neurons lost to the age-related neurodegenerative processes driving Parkinson's disease (PD). ... The promise of this approach has been foreshadowed in murine models of PD, in which DA neurons derived from mouse [embryonic stem cells] have been found highly effective in reversing motor symptoms. But the performance of ostensibly DA neurons derived from human pluripotent stem cells in the same systems has so far been poor, due to uncertain and unstable differentiation of the cells. In a new study, a team of researchers [have] used their novel DA neuron differentiation strategy to resolve these difficulties, leading to robust and stable engraftment of human pluripotent stem cell-derived DA neurons into the striatum and substantial evidence of efficacy in two rodent models of the disease, and provided preliminary data on the viability of their approach in nonhuman primates."

Monday, November 28, 2011
Researchers continue to pick out specific biochemical differences that may contribute to the unusual longevity of the naked mole rat: "Naked mole-rats (Heterocephalus glaber), the longest-lived rodents, live 7-10 times longer than similarly-sized mice and exhibit normal activities for ∼75% of their lives. Little is known about the mechanisms that allow them to delay the aging process and live so long. Neuregulin-1 (NRG-1) signaling is critical for normal brain function during both development and adulthood. We hypothesized that long-lived species will maintain higher levels of NRG-1 and that this contributes to their sustained brain function and concomitant maintenance of normal activity. We monitored the levels of NRG-1 and its receptor ErbB4 in H. glaber at different ages ranging from 1 day to 26 years and found that levels for NRG-1 and ErbB4 were sustained throughout development and adulthood. In addition, we compared seven rodent species with widely divergent (4-32y) maximum lifespan potential (MLSP) and found that at a physiologically-equivalent age, the longer-lived rodents had higher levels of NRG-1 and ErbB4. Moreover, phylogenetic independent contrast analyses revealed that this significant strong correlation between MLSP and NRG-1 levels was independent of phylogeny. These results suggest that NRG-1 is an important factor contributing to divergent species MLSP through its role in maintaining neuronal integrity."

Monday, November 28, 2011
The mainstream of aging research is only interested in slowing aging through manipulation of metabolic processes, rather than trying to reverse aging through repair biotechnologies. Here is a look at the breadth of that potential research: "Aging is the major biomedical challenge of this century. The percentage of elderly people, and consequently the incidence of age-related diseases such as heart disease, cancer, and neurodegenerative diseases, is projected to increase considerably in the coming decades. Findings from model organisms have revealed that aging is a surprisingly plastic process that can be manipulated by both genetic and environmental factors. Here we review a broad range of findings in model organisms, from environmental to genetic manipulations of aging, with a focus on those with underlying gene-environment interactions with potential for drug discovery and development. One well-studied dietary manipulation of aging is caloric restriction, which consists of restricting the food intake of organisms without triggering malnutrition and has been shown to retard aging in model organisms. Caloric restriction is already being used as a paradigm for developing compounds that mimic its life-extension effects and might therefore have therapeutic value. The potential for further advances in this field is immense; hundreds of genes in several pathways have recently emerged as regulators of aging and caloric restriction in model organisms. Some of these genes, such as IGF1R and FOXO3, have also been associated with human longevity in genetic association studies. The parallel emergence of network approaches offers prospects to develop multitarget drugs and combinatorial therapies. Understanding how the environment modulates aging-related genes may lead to human applications and disease therapies through diet, lifestyle, or pharmacological interventions. Unlocking the capacity to manipulate human aging would result in unprecedented health benefits."



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