LONGEVITY MEME NEWSLETTER
April 14 2008
The Longevity Meme Newsletter is a weekly e-mail containing news, opinions and happenings for people interested in healthy life extension: making use of diet, lifestyle choices, technology and proven medical advances to live healthy, longer lives.
- More To Blame on Damaged Mitochondrial DNA
- The Other Side of Stem Cell Research
- Latest Healthy Life Extension Headlines
MORE TO BLAME ON DAMAGED MITOCHONDRIAL DNA
Mitochondria are the power plants of your cells, busy machines working to repackage the energy in food molecules into other forms. All machinery wears down with use, however. As time advances, damaged mitochondrial DNA becomes dominant in a small but important fraction of your cells, causing the mitochondria to switch to a less efficient mode of generating energy. This in turn causes these cells to export large numbers of reactive, damaging molecules throughout the body, contributing to many of the diseases and degenerations of aging. This is the mitochondrial free radical theory of aging in a nutshell:
As it turns out, damaged mitochondrial DNA may be at the root of other changes in aging as well. For example, evidence suggests that mitochondrial DNA damage is associated with the age-related slowdown in processes that repair nuclear DNA damage:
Also, consider the evidence for advancing mitochondrial DNA damage to accelerate the well-known shortening of telomeres with age, driving more cells into a senescent state that can damage surrounding tissue:
Now to add to all that, we have a recently discovered association between mitochondrial DNA damage and metastasis in cancer:
"Cancer often strikes its final, fatal blow when a tumor spreads to other organs. A new study sheds light on this poorly understood process, called metastasis. The researchers report that mutations in mitochondrial DNA can spur metastasis."
There's more to aging than just faulty mitochondria, but we should all be happy to see so much piled atop just one cause. The discovery of more benefits that could result from repair of mitochondria means a greater likelihood of significant funding for medical technologies capable of achieving that end. Any connection to cancer research, given the size of that field, raises the chances considerably.
When it comes to wholesale replacement of damaged mitochondria or mitochondrial DNA, progress has been very promising in recent years - with the important exception of the money side of the research equation. It has been several years since protofection of new mitochondrial DNA was demonstrated to work in mice, for example, and other groups have shown similar results via mechanisms discovered in tropical parasites. The state of funding in no way matches the potential for this sort of research, however.
Consider that it takes 30 years or more of life and wear for your mitochondria to become damaging to long-term health. With a single application of a working method of protofection in humans, replacing all mitochondrial DNA with an undamaged version, it is plausible to think that we could entirely remove this significant contribution to age-related degeneration for an additional 30 years. I think that merits a great deal of attention.
THE OTHER SIDE OF STEM CELL RESEARCH
There's more to stem cell research than tissue engineering and regenerative medicine:
"When I talk about stem cell science, it's usually in the context of goals in tissue engineering and regenerative medicine, especially as they apply to repairing the damage of aging. Organ regrowth, scalable production of large numbers of tailored cells, autologous cell therapies, and so forth. There's a whole other side to stem cell research, however: making it easier and less costly to both understand disease mechanisms and test therapies in the laboratory. If researchers can reliably use therapeutic cloning - or other methods - to produce pluripotent cells from adult cells, then limits placed on the study of disease mechanisms due to scarity of cell samples vanish."
The highlights and headlines from the past week follow below.
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LATEST HEALTHY LIFE EXTENSION HEADLINES
To view commentary on the latest news headlines complete with links and references, please visit the daily news section of the Longevity Meme: http://www.longevitymeme.org/news/
50 Years of the Free Radical Theory of Aging (April 11 2008)
The free radical theory of aging - which evolved into the mitochondrial free radical theory of aging - has been around for a while. Via Ouroboros: "Understanding the molecular mechanisms underlying the ageing process may provide the best strategy for addressing the challenges posed by ageing populations worldwide. One theory proposing such molecular mechanisms was formulated 50 years ago. Harman et al. suggested that ageing might be mediated by macromolecular damage through reactions involving reactive oxygen species (ROS). Today, a version of the free radical theory of ageing, focusing on mitochondria as source as well as target of ROS, is one of the most popular theories of ageing. Here we critically review the status of key principles and concepts on which this theory is based. We find that the evidence to date shows that many of the original assumptions are questionable, while on some critical issues further refinements in techniques are required. Even so, it is becoming evident that mitochondria and [mitochondrial DNA] integrity may indeed be crucial determinants of organismal ageing."
Cartilage Regeneration Versus Arthritis (April 11 2008)
EurekAlert! notes that researchers have "successfully identified stem cells within articular cartilage of adults, which although it cannot become any cell in the body like full stem cells, has the ability to derive into chondrocytes - the cells that make up the body's cartilage - in high enough numbers to make treatment a realistic possibility. The team have even been able to identify the cells in people over 75 years of age. Osteoarthritis [occurs] when changes in the make up of the body's cartilage causes joints to fail to work properly. At its worse it can cause the break up of cartilage, causing the ends of the bones in the joint to rub against each other. This results in severe pain and deformation of the joint. One current treatment to treat damaged cartilage due to trauma in younger patients is to harvest cartilage cells from neighbouring healthy cartilage and transplant them into the damaged area. Unfortunately, only a limited number of cells can be generated. ... We have identified a cell which when grown in the lab can produce enough of a person's own cartilage that it could be effectively transplanted. There are limitations in trying to transplant a patient's existing cartilage cells but by culturing it from a resident stem cell we believe we can overcome this limitation."
The Value of Exercise (April 10 2008)
Every year you can extend your natural healthy longevity is a year more for the scientific community to develop working rejuvenation medicine. Regular exercise certainly helps, but be wary of hype like "chop a dozen years off the biological age." Exercise is not proven to do any such thing, but it does make some biomarkers of fitness return to the levels of a person 12 years younger. Exercise also helps to avoid damage caused by a sedentary lifestyle through a variety of processes, varying from dropping excess visceral fat to changing the regulation of metabolism: "aerobic fitness may indirectly delay dependency by preventing other conditions that are likely to diminish functional capacity, including obesity, diabetes, hypertension, myocardial infarction, stroke, some forms of cancer, and osteoporosis. Exercise also hastens recovery from injuries and any additional muscle power may prevent falls, he said. ... There seems good evidence that the conservation of maximal oxygen intake increases the likelihood that the healthy elderly person will retain functional independence."
Scaffolding For Brain Regeneration (April 10 2008)
From EurekAlert!: "Inserting tiny scaffolding into the brain could dramatically reduce damage caused by strokes ... combining scaffold microparticles with neural stem cells (NSCs) could regenerate lost brain tissue. Strokes cause temporary loss of blood supply to the brain which results in areas of brain tissue dying - causing loss of bodily functions such as speech and movement. ... while NSC transplantation has been proven to improve functional outcomes in rats with stroke damage little reduction in lesion volume has been observed. ... Working with rats [researchers] are developing cell-scaffold combinations that could be injected into the brain to provide a framework inside the cavities caused by stroke so that the cells are held there until they can work their way to connect with surrounding healthy tissue. ... The ultimate aim is to establish if this approach can provide a more efficient and effective repair process in stroke."
Replacing Damaged Retinas With Silicon (April 09 2008)
Progress continues in the components of prosthetic sight, with replacements for age-damaged retinas being the most advanced at this time. The latest versions are a few years from human trials, and the result is far from a full restoration of vision, but it's a great improvement over blindness. The technology will only get better with time: "The implant is based on a small chip that is surgically implanted behind the retina, at the back of the eyeball. An ultra-thin wire strengthens the damaged optic nerve; its purpose is to transmit light and images to the brain's vision system, where it is normally processed. Other than the implanted chip and wire, most of the device sits outside the eye. The users would need to wear special eye glasses containing a tiny battery-powered camera and a transmitter, which would send images to the chip implanted behind the retina. The new device is expected to be quite durable, since the chip is enclosed in a titanium casing, making it both water-proof and corrosion-proof. The researchers estimate that the device will last for at least 10 years inside the eye."
Scaling Provision of Stem Cells (April 09 2008)
Large scale progress in research and clinical application of stem cell therapies requires an industry of cell provision. The MIT Technology Review profiles the efforts of BioTime to be a provider: "Stem cells hold great promise for medicine, both as a potential source of replacement cells for damaged organs and as a scientific resource to study disease and develop and test new drugs. But to realize that promise, scientists have to figure out how to make their products on an industrial scale. ... It's clear we'll need a much better strategy for reliably and reproducibly generating large numbers of specific cell types. Most studies until now have stopped short of doing this ... I could clearly see a customer base in scientists who simply see stem cells as a way of providing lots of cells for their use ... Currently, scientists prod stem cells to develop into specific cell types by exposing them to some of the same chemicals those cells would encounter during normal development. However, the process is often inefficient, yielding a small number of the desired cells that must then be purified from other cell types. ... BioTime is already gearing up commercial manufacturing, aiming to begin shipping cells in six to 12 months."
An Interesting Use of Targeted Immmunotherapy (April 08 2008)
Biotechnologies that allow targeting of very specific cell types are a powerful and versatile tool, as demonstrated in this application via Reuters: "Although human embryonic stem cells are a very powerful source to make differentiated cells, like heart cells, the problem is that you can have residual cells and there is a safety concern because they can form [a] mass of tumour cells ... So if you give a product that is 95 percent heart cells, but 5 percent embryonic stem cells, it may be a problem later on ... The researchers managed to generate antibodies in mice after injecting human embryonic stem cells into the animals. The antibodies were then harvested and added to cultured embryonic stem cells that had been newly differentiated on laboratory dishes. ... [the antibody] specifically eliminated undifferentiated cells within 30 minutes but left differentiated cells untouched." So here, tools developed in cancer research are turned to making a foundation for regenerative medicine more practical.
Putting IPS Cells Through Their Paces (April 08 2008)
As reported at EurekAlert!, researchers are testing induced pluripotency (IPS) in areas in which stem cell therapies have already shown potential. Can the more readily engineered IPS cells do the job? "Neurons derived from reprogrammed adult skin cells successfully integrated into fetal mouse brains and reduced symptoms in a Parkinson's disease rat model ... This is the first demonstration that reprogrammed cells can integrate into the neural system or positively affect neurodegenerative disease ... For the neural experiments Wernig used induced pluripotent stem cells (IPS cells), which were created by reprogramming adult skin cells using retroviruses to express four genes (Oct4, Sox2, c-Myc and Klf4) into the cells' DNA. The IPS cells were then differentiated into neural precursor cells and dopamine neurons using techniques originally developed in embryonic stem cells. ... Wernig saw that transplanted cells formed clusters where they had been injected and then migrated extensively into the surrounding brain tissues. ... the neural precursor cells that migrated had differentiated into several subtypes of neural cells, including neurons and glia, and had functionally integrated into the brain."
The Limits of Regenerative Medicine (April 07 2008)
All too many efforts aimed at treating age-related disease are nothing more than brief patches for the problem - treat the symptoms but not the cause for a small gain. Regenerative medicine sometimes falls into this category: researchers "have discovered that dopamine cells that have been transplanted into the brain of patients with Parkinson disease [PD] develop pathologic changes characteristic of [PD] and do not appear to function normally ... Dopamine cells are transplanted into the brain of PD patients in the hope that they can replace those that degenerate and thereby improve symptoms of the disease. This study shows that implanted cells can become affected by the disease process and thereby limits the long-term utility of this approach. ... In the study, the patient improved initially but then deteriorated. ... these findings suggest that the disease process is ongoing and can damage newly implanted cells." When all you can do is patch, you patch, but we're moving into a more capable era now. We should aim higher, at eliminating root causes.
Preview Ending Aging At Google Books (April 07 2008)
You can now preview Ending Aging at Google Books: "Nearly all scientists who study the biology of aging agree that we will someday be able to substantially slow down the aging process, extending our productive, youthful lives. Dr. Aubrey de Grey is perhaps the most bullish of all such researchers. ... Dr. de Grey believes that the key biomedical technology required to eliminate aging-derived debilitation and death entirely - technology that would not only slow but periodically reverse age-related physiological decay, leaving us biologically young into an indefinite future - is now within reach. In Ending Aging, Dr. de Grey and his research assistant Michael Rae describe the details of this biotechnology. They explain that the aging of the human body, just like the aging of man-made machines, results from an accumulation of various types of damage. As with man-made machines, this damage can periodically be repaired, leading to indefinite extension of the machine's fully functional lifetime, just as is routinely done with classic cars. We already know what types of damage accumulate in the human body, and we are moving rapidly toward the comprehensive development of technologies to remove that damage."