Healthy Life Extension
A Stem Cell Secret Revealed
posted on April 10th, 2012
Dear Future Centenarian,
Stem cell technology will the biggest thing to ever hit medicine. As it matures, it will have an unimaginable impact on the health and well-being of hundreds of millions.
The niche in which stem cells live is arguably more important in the aging of tissues than the stem cells themselves. But what exactly is it, and why does it matter so much? Here is an introduction:
Stem cell populations in the body live in stem cell niches, environment or milieu. Each different type of stem cell resides within its own niche.
The niche supplies the necessary environment and many of the cues that direct stem cell activity. This is why changes in the niche are possibly more important than changes in stem cells themselves when it comes to the decline of stem cell activity with aging.
That decline causes a sort of corrosion of your tissues as stem cells increasingly fail to keep up with maintenance and repair. But the evidence to date suggests that those stem cells are generally still capable of doing their jobs, provided they are given their marching orders.
Ideas about stem cells, and how they behave, have been undergoing a lot of change in recent years, thanks to developments in visualizing, monitoring, and manipulating cells and tissues. The detailed mechanisms underlying niche function are extremely varied. Niches may be composed of cells, or cells together with extracellular structures such as the extracellular matrix (ECM).
They may be sources of secreted or cell surface factors that control stem cell renewal, maintenance, or survival. They may consist of just a single cell type, or a whole host of interacting cells. They may derive from cells outside the stem cell's lineage, or they may derive primarily from the stem cell's own descendents.
In general, there seems to be much more consensus about the fact that stem cells invariably need niches than about the specific mechanisms by which niches do their jobs.
Why should a stem cell need a special environment? This is a pertinent question, given that none of the elementary processes that stem cells rely upon¦ growing, dividing, differentiating¦ are unique to stem cells.
Research marches on. And stem cell based regenerative medicine may be your first and most important path to extreme longevity. Most important, because it may keep you ticking until full rejuvenation is possible.
Meanwhile¦ take care of yourself and stay here to take advantage of these emerging miracles..
LATEST HEADLINES FROM FIGHT AGING!
GROWING STEM CELLS INTO LUNG TISSUE Friday, AprilÂ 6, 2012 http://www.fightaging.org/archives/2012/04/growing-stem-cells-into-lung-tissue.php
An example of work that lays the foundations for lung tissue engineering, which has been lagging behind advances for other organs: "How do you grow stem cells into lungs? The question has puzzled scientists for years. First you need the right recipe, and it took [researchers] seven years of trial and error and painstaking science to come up with it.
Some tissues, like muscle and nerves, are relatively easy to grow, but others, including liver, lung, thyroid, and pancreas, have been much more difficult. These troublesome tissues all spring from the endoderm, the innermost layer of an early embryo. The endoderm forms when an embryo is about three weeks old and differentiates into organs as early as five weeks. Somehow, in these two weeks the endoderm transforms into differentiated organs as diverse as the lungs and the stomach.[Researchers] decided to create a knock-in reporter gene that would glow green during the 'fate decision' - the moment when the stem cells expressed a gene called Nkx2-1 and thereby took a step toward becoming lungs. This allowed the team to track the cells as they developed, mapping each of the six critical decisions on the path to lung tissue. Once [the] team had grown what appeared to be lung cells, they had to make sure they had the recipe right. They took samples of mouse lungs and rinsed them with detergent until they became cell-free lung-shaped scaffolds.
They seeded one lung with 15-day-old homegrown lung cells that they had purified from stem cells. As a control, they seeded another lung with undifferentiated embryonic stem cells. Within 10 days after seeding, the lung cells organized themselves and populated the lung, creating a pattern recognizable [as] lung tissue. A happy side effect of the discovery was that the scientists also mapped out the road from stem cell to thyroid. [The] thyroid, it turns out, also comes from the endoderm layer, deriving from a progenitor that expresses the same key gene as lung progenitors. [The] work will likely have a huge impact on lung stem cell researchers, who have been waiting for a discovery like this to propel their research on inherited lung disease."
CALORIE RESTRICTION AND LONGEVITY Wednesday, AprilÂ 4, 2012 http://www.fightaging.org/archives/2012/04/calorie-restriction-and-longevity.php
An introduction to calorie restriction at h+ Magazine: "In the early twentieth century nutrition researchers found that rats maintained on reduced caloric intake showed lower spontaneous tumors compared to rats fed ad libitum (allowed to eat as much as they chose). Although this work did not address caloric restriction (CR) and aging, it suggested that CR might slow the onset of age-associated disease in rodents.
Numerous follow-up studies demonstrated that a micronutrient adequate CR diet significantly increased the lifespan of many species, largely crossing species boundaries.Â While CR increases the lifespans of most species examined, it also suppresses many of the diseases associated with human aging, thus increasing the 'health-span.' Over short periods, CR lowers blood pressure, heart rate, and glucose levels, and improves memory in older individuals and measures of cognitive performance in animals.
Over longer periods CR significantly reduces the risk for many different types of cancer, age-related brain atrophy, heart disease (and atherosclerosis related diseases), autoimmune disease, and adult onset diabetes. CR appears to lessen the risk for, and attenuates or even reverses the symptoms of Alzheimer's and possibly Parkinson's diseases; two major age-related neurodegenerative diseases that cause enormous human suffering.
Interestingly, CR appears to promote the progression of Amyotrophic Lateral Sclerosis (Lou Gehrig's disease), indicating it does not protect from all human diseases.
Aging causes extensive, often organ-specific changes in gene expression patterns. Analysis [has] shown that aging, calorically restricted mice show gene expression patterns resembling those of young animals, compared to ad libitum-fed mice of the same age. CR also lowers cellular oxidative damage by reducing mitochondrial oxygen free radical production, lessens age-related telomere shortening, lowers inflammation, increases DNA damage repair efficiency and lowers damage to DNA and RNA (thus promoting genomic stability), lowers insulin levels while promoting insulin sensitivity, reduces the number of senescent (non-dividing) cells that accumulate with aging, attenuates age-related cellular protein cross-linking, and increases the removal of damaged cellular proteins - a process called 'autophagy' which declines with age and plays a role in resistance to infection, cancer, heart disease, and neurodegeneration. "
CAN NEURAL STEM CELLS ADDRESS COGNITIVE DECLINE? Wednesday, AprilÂ 4, 2012 http://www.fightaging.org/archives/2012/04/can-neural-stem-cells-address-cognitive-decline.php
An open access review paper: "Several studies suggest that an increase in adult neurogenesis has beneficial effects on emotional behavior and cognitive performance including learning and memory. The observation that aging has a negative effect on the proliferation of neural stem cells has prompted several laboratories to investigate new systems to artificially increase neurogenesis in senescent animals as a means to compensate for age-related cognitive decline.
Recent evidences indicate that the relative abundance of stem cells in certain organs does not necessarily correlate with their impact on organ function. Specifically, the mammalian brain is perhaps the organ with the lowest regenerative potential but the one in which the signs of aging are more manifested. Using the words of the renaissance writer Michel de Montaigne, 'age imprints more wrinkles on the mind than it does on the face' indicating that age-related cognitive decline has the highest impact on the quality of life.
To which extent this decline is dependent on neural stem and progenitor cells (together referred to as NSCs) is hard to tell but growing evidences indicate that, despite their negligible numbers, the few resident NSCs that are located in specific brain regions, most notably the subgranular zone of the hippocampus, seem to play a major role in cognitive functions such as learning, memory, and emotional behavior by generating, through intermediate progenitors, neurons that are constantly added to the brain circuitry throughout life. The available data strongly suggests that aging almost exclusively acts at the level of NSC proliferation. Yet, the many contradicting results and uncertainties on identifying the exact causes of this 'decreased proliferation' [need] to be fully acknowledged in order to give a rigorous and meaningful direction to this relatively new field. The fact that NSCs can efficiently respond to physiological and pathological stimuli to increase neurogenesis indicates that stimulation of endogenous NSCs offers a promising alternative to transplantation approaches that until now were intensely investigated."
WORK ON REVERSING SCAR TISSUE IN THE HEART Tuesday, AprilÂ 3, 2012 http://www.fightaging.org/archives/2012/04/work-on-reversing-scar-tissue-in-the-heart.php
A look at some of the research aimed at reversing the damage caused by heart attacks: "Our ultimate hope is that, during the acute period followingÂ myocardial infarction (MI), patients will be able to receive direct injections of factors that transform the existing fibroblast cells in the 'scar' into new myocytes. The resulting increase in muscle mass should help MI survivors to live more normal lives.
When heart muscle cells become injured and die following an MI, patients have the major problem that these cells have little or no capacity for regeneration. Part of the process of remodelling that occurs following the injury is that fibroblast cells migrate to the site and create the scar. The process at first can be considered beneficial since without fibroblasts adding structural support damaged hearts would rupture. But later difficulties arise when the fibrotic scar doesn't contract like the muscle it has replaced. Reduced global contractility means the heart has to work much harder, and the extra stress can ultimately lead to heart failure and even death.
One of the Holy Grails of cardiovascular research has been to replace these lost myocytes and return functionality to the heart. Some of the first approaches to be investigated were the introduction of stem or progenitor cells to the sites of injury. But many hurdles have been encountered including getting cells to integrate with neighboring cells in the heart, and there have been concerns that residual 'rogue' cells could persist with the potential to keep dividing and give rise to tumors. Harnessing the vast reservoir of fibroblasts already present in the heart, we felt, could overcome many of these issues. They've the big advantage they're already present in the organ and closely integrated with neighbouring cells.
The team were able to identify three [genes] Gata4, Mef2c, and Tbx5 that could convert fibroblasts taken from the hearts of adult mice into new myocytes. In the second part of the study, the team injected fibroblasts that already had the three genes inserted directly into the scar tissue of mice. They were able to show the fibroblasts differentiated into cardiomyocyte-like cells. The fibroblasts converted into cells with nice patterns of striations, typical of myocytes, and developed units that could generate force. In the latest study [they] have been able to take the process one step further by injecting a viral vector encoding the genes for Gata4, Mef2c, and Tbx5 directly into the scar tissue of mice who had just experienced an MI. With these studies we've obtained even better results showing that the fibroblasts become more like cardiomyocytes and functionally couple with their neighbors. They could beat in synchrony and improve the function of the heart."
INTERVENING IN THE MECHANISMS OF MEMORY LOST TO AGING Tuesday, AprilÂ 3, 2012 http://www.fightaging.org/archives/2012/04/intervening-in-the-mechanisms-of-memory-lost-to-aging.php
Via ScienceDaily: scientists "have shown in animal models that the loss of memory that comes with aging is not necessarily a permanent thing. [Researchers] took a close look at memory and memory traces in the brains of both young and old fruit flies. What they found is that like other organisms - from mice to humans - there is a defect that occurs in memory with aging.
In the case of the fruit fly, the ability to form memories lasting a few hours (intermediate-term memory) is lost due to age-related impairment of the function of certain neurons. Intriguingly, the scientists found that stimulating those same neurons can reverse these age-related memory defects. This study shows that once the appropriate neurons are identified in people, in principle at least, one could potentially develop drugs to hit those neurons and rescue those memories affected by the aging process.
In addition, the biochemistry underlying memory formation in fruit flies is remarkably conserved with that in humans so that everything we learn about memory formation in flies is likely applicable to human memory and the disorders of human memory. Olfactory memory, which was used by the scientists, is the most widely studied form of memory in fruit flies - basically pairing an odor with a mild electric shock. These tactics produce short-term memories that persist for around a half-hour, intermediate-term memory that lasts a few hours, and long-term memory that persists for days.
The team found that in aged animals, the signs of encoded memory were absent after a few hours. In that way, the scientists also learned exactly which neurons in the fly are altered by aging to produce intermediate-term memory impairment. The scientists took the work a step further and stimulated these neurons to see if the memory could be rescued. To do this, the scientists placed either cold-activated or heat-activated ion channels in the neurons known to become defective with aging and then used cold or heat to stimulate them. In both cases, the intermediate-term memory was successfully rescued."
IMMUNE THERAPIES TO REDUCE ATHEROSCLEROSIS Monday, AprilÂ 2, 2012 http://www.fightaging.org/archives/2012/04/immune-therapies-to-reduce-atherosclerosis.php
Via EurekAlert!: "injecting cardiovascular disease (CVD) patients with vaccines and monoclonal antibodies to combat atherosclerosis could soon change the treatment landscape of heart disease. Both approaches [can] be considered truly ground breaking since for the first time they target the underlying cause of CVD. With phase 2a trials on recombinant antibodies currently ongoing, [such] treatments could soon become a clinical reality.
If all goes well, the first in class of these treatments could be licensed within four to five years. Established therapies against atherosclerosis almost exclusively focus on risk factor modification - that is reduction of dyslipidaemia, hypertension and hyperglycaemia. It was in the early 1990s that identification of antibodies against oxidized low density lipoproteins (LDL) in artery plaques, first gave rise to the concept that CVD might be an autoimmune disease where the immune system attacks oxidised LDL.
Since it is impractical to develop vaccines based on oxidized LDL (due to difficulty of standardizing the particle) [researchers] looked to identify structures within the oxidized LDL that triggered the desired protective response. The team were able to identify three [peptides], which when formulated with a carrier and adjuvant, reduced development of atherosclerosis in mice by 60 to 70%. Further along the development pathway, and already in clinical trials, is an altogether different immune approach involving injection of antibodies directly targeting oxidized LDL.
The rationale is that since oxidized LDL plays a major role in the development of atherosclerotic plaques and harmful inflammatory processes, directly targeting oxidized LDL should prevent plaque formation and reduce inflammation. Preclinical studies show that administration of the BI-204 monoclonal antibody [reduced] the formation of atherosclerotic plaques and plaques already present by 50%. In the phase I study, which took place in 80 healthy volunteers with elevated levels of LDL, BI-204 was found to be safe and well tolerated. Now for the current phase 2a double blind [study], BI-204 is being delivered intravenously to 144 patients with stable coronary artery disease in addition to standard care."
THE EARLY DEVELOPMENT OF SYNTHETIC CELLS Monday, AprilÂ 2, 2012 http://www.fightaging.org/archives/2012/04/the-early-development-of-synthetic-cells.php
Artificial cells will be useful tools in the medicine of tomorrow: "Daniel Hammer, professor of chemical engineering and biological engineering at the University of Pennsylvania, is building white blood cells in the lab from plastics that can act as artificial cell walls.
Think of a gel capsule of your preferred headache medicine but on a much smaller scale and with a programmable molecular brain. These synthetic cells, known as leuko-polymersomes, could one day deliver the latest cancer-killing drugs directly to a tumor or send out a chemical beacon that signals natural white blood cells to come and join the fight against a disease.Â Ultimately I think that we could program these cells to do things that we never thought white blood cells could do.
Instead of boosting immune response, for example, Hammer envisions synthetic cells that could act as inhibitors to the body's defenses, providing relief for people suffering from autoimmune disorders. Hammer has been studying how to turn plastics into cellular structures for more than a decade, but it's just in the past few years that the field has kicked into high gear. His team is learning to mimic the targeting capabilities that let natural white blood cells take the fight to viruses and bacteria - what Hammer describes as a kind of 'molecular zip coding' - and the adhesive properties that let them stand their ground when they arrive. In 2010, Hammer and colleagues from Duke University designed synthetic molecules shaped like the receptors white blood cells use to find and adhere to inflamed tissue. In-vitro tests showed that synthetic cells could seek out inflamed tissue and stick to it once they arrived."