Longevity Meme Newsletter, July 05 2010

July 05 2010

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.



- Regenerative Healing of Cavities in Teeth
- The Mess of Modern Medicine
- An Update on Progeria Research
- Discussion
- Latest Healthy Life Extension Headlines


The dental application of regenerative medicine is one of the more advanced areas in this field of research. Whole teeth have been grown from stem cells in animal studies, and here scientists demonstrate healing of cavities by regrowth of tooth enamel:


"A new peptide, embedded in a soft gel or a thin, flexible film and placed next to a cavity, encourages cells inside teeth to regenerate in about a month ... The gel or thin film contains a peptide known as MSH, or melanocyte-stimulating hormone. Previous experiments [showed] that MSH encourages bone regeneration. Bone and teeth are fairly similar, so the French scientists reasoned that if the MSH were applied to teeth, it should help healing as well. To test their theory, the French scientists applied either a film or gel, both of which contained MSH, to cavity-filled mice teeth. After about one month, the cavities had disappeared."


While we live in an age of progress in medical science, never forget that this progress is far slower than it might be, thanks to government regulation:


"We live in an age in which personal accountability is a distant, unpracticed concept. It is taken for granted that every possible personal decision is open to socialization, and that any cost might be paid for by some distant other. People follow incentives, and when the incentives have been structured so as to eliminate the need for frugality, then waste and corruption inevitably follows. This is the rot that slays civilizations, and it will destroy the American empire just as surely as it did the British Empire and Rome.

"We can see this corrosion underway most clearly in the centralized medical command and control infrastructures of the Western world. Unlike almost all other areas of technology, costs in medicine keep spiraling upward - and this should not be a surprise given the perverse incentives embedded in the system. Costs paid by other people. Services divorced from price considerations by the customer. Lack of competition. Use of regulators and the legalized bribery of lobbying to gain advantage in the marketplace, rather than research and development or price-cutting. And so forth.

"There is a very simple solution to the problems of medicine. It's called freedom: freedom for providers to develop and compete as they see fit, and freedom for people to choose or reject their offerings with the money in their own pockets and savings accounts. For progress and efficiency to reign in an industry, people have to pay for goods with their own funds, and providers have to be free to innovate. Competition and the care with which people manage their own money keeps both sides as honest as any human culture is going to be.

"Look at fashion. Shoes. Computers. DNA sequencing. Or any one of a thousand other important goods whose value has fallen over time and continues to do so. These are less regulated markets, not stifled and buried beneath chains like the provision of medicine. They are vibrant, constantly innovating and competing, and this is exactly because people pay for these products with the money they care about most."


Progeria is perhaps the best known of the accelerated aging conditions, and great strides have been made in understanding its biochemistry in recent years. Similarities exist between abnormalities associated with progeria and those observed to a lesser degree in
"normal" aging. It seems possible that a therapy for progeria may also have some modest benefit in treating normal aging:


"Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare premature aging disorder caused by a [mutation within the] LMNA gene encoding A-type nuclear lamins. [Nuclear lamins are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus.] ... several studies suggest that abnormal [lamins] may accumulate in normal aging.

"At this stage it is unknown to what degree the observed changes in lamins in the elderly contribute to the degenerations of aging. It is certainly the case that an accumulation of damaged or malformed proteins of all sorts is noted in aging; the lamins may or may not be significant in comparison to others. But the right approach to aging is to work towards reversing all changes that cannot be positively identified as secondary effects: aim to repair and restore every fundamental change."


The highlights and headlines from the past week follow below.

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From Wired: "Blood drawn with a simple needle stick can be coaxed into producing stem cells that may have the ability to form any type of tissue in the body, three independent papers report... The new technique will allow scientists to tap a large, readily available source of personalized stem cells. ... Because taking blood is safe, fast and efficient compared to current stem cell harvesting methods, some of which include biopsies and pretreatments with drugs, researchers hope that blood-derived stem cells could one day be used to study and treat diseases. ... Three research groups used similar methods to prod certain immune cells in human blood to become induced pluripotent stem cells. Because they are reprogrammed adult cells, these stem cells share many of the same regenerative abilities as true embryonic stem cells but may not have as much versatility. ... Scientists' manipulations turned the stem cells in the new studies into several types of mature blood cells, including infection-fighting T cells. What's more, all the groups showed that a batch of the stem cells implanted into mice developed into the three main types of progenitor cells found in human embryos."

Via ScienceNews: "In the new study, researchers looked at genetic markers called single nucleotide polymorphisms, or SNPs, in 1,055 centenarians and 1,267 younger people, all of European descent. The scientists found 150 genetic SNP variants linked to extreme longevity. Initially, the team identified only 33 SNPs found more often in people aged 90 to 114 years but not in a control group made up of people who will presumably live an average lifespan. ... biostatistician Paola Sebastiani [devised] a different statistical method to identify additional SNPs that would improve the team's ability to predict longevity. The team tested their predictions on a separate group of centenarians and controls. With the 150 SNPs, the researchers could correctly predict who was a centenarian 77 percent of the time. ... Now on one side, 77 percent is a very high accuracy for a genetic model, which means that the traits that we are looking at have a very strong genetic base ... On the other hand, the 150 SNPs can't explain why the remaining 23 percent of centenarians in the study have reached such ripe old ages. It could mean that those people have other, rare genetic variants or lifestyles responsible for their longevity or some combination of the two."

As the Smithsonian notes, "It won't be long before surgeons routinely install replacement body parts created in the laboratory. ... Anthony Atala works in the body shop of the future. ... he and his colleagues use human cells to grow muscles, blood vessels, skin and even a complete urinary bladder. Much of the work is experimental and hasn't yet been tested in human patients, but Atala has implanted laboratory-grown bladders into more than two dozen children and young adults born with defective bladders that don't empty properly, a condition that can cause kidney damage. The bladders were the first lab-generated human organs implanted in people. If they continue to perform well in clinical tests, the treatment may become standard not only for birth defects of the bladder but also for bladder cancer and other conditions. ... Regenerative medicine's once-wild ideas are fast becoming reality. Late last year, Organovo, a biotech company in San Diego, began distributing the first commercially available body-part printer. Yes, you read correctly: a printer for body parts. Using the same idea as an ink-jet printer, it jets laser-guided droplets of cells and scaffold material onto a movable platform. With each pass of the printer head, the platform sinks, and the deposited material gradually builds up a 3-D piece of tissue. Regenerative medicine laboratories around the world have relied on the printer to generate pieces of skin, muscle and blood vessels. Atala's lab has used the technology to construct a two-chambered mouse-size heart in about 40 minutes."

Some people have demonstrably better mitochondrial DNA, others worse. Here, a study shows correlations between some variants and old-age frailty: "Mitochondria contribute to the dynamics of cellular metabolism, the production of reactive oxygen species, and apoptotic pathways. Consequently, mitochondrial function has been hypothesized to influence functional decline and vulnerability to disease in later life. ... mitochondrial DNA (mtDNA) variation was compared in frail and non-frail older adults. Associations of selected SNPs with a muscle strength phenotype were also explored. Participants were selected from the Cardiovascular Health Study (CHS), a population-based observational study ... Three mtDNA SNPs were statistically significantly associated with frailty across all pilot participants or in sex-stratified comparisons." Given the degree to which mitochondrial composition correlates with species life span differences, we should not be surprised to find some variations significant in human life span.

Researchers are gathering evidence to suggest that stem cells from the old are less useful when transplanted - which means that some form of repair or other manipulations may need to be included in future stem cell therapies for the degenerative conditions of aging: "Clinical trials of cardiac cell therapy have indicated limited benefits in aging patients, even though preclinical studies using young animals consistently reported significant improvements. Animal studies have demonstrated reduced efficacy of donor cells isolated from older individuals. Here, we evaluated the effects of donor age on the function of human mesenchymal stem cells (hMSCs) in the context of cell therapy for ischemic cardiomyopathy. ... The regenerative capacity of hMSCs was significantly influenced by age. Transplanting young hMSCs improved functional outcomes after an MI by preventing matrix degradation and promoting angiogenesis. The clinical implication is that aged patients require an optimized source of stem cells for treatment."

Crayfish species, like lobsters, appear not to age in any easily measurable way. As for the study of other long-lived species, perhaps there is something to be learned here: "The marbled crayfish is an emerging laboratory model for development, epigenetics and toxicology that produces up to 400 genetically identical siblings per batch. It is easily cultured, has an adult size of 4-9 cm, a generation time of 6-7 months and a life span of 2-3 years. Experimental data and biological peculiarities like isogenicity, direct development, indeterminate growth, high regeneration capacity and negligible senescence suggest that the marbled crayfish is particularly suitable to investigate the dependency of ageing and longevity from non-genetic factors such as stochastic developmental variation, allocation of metabolic resources, damage and repair, caloric restriction and social stress. It is also well applicable to examine alterations of the epigenetic code with increasing age and to identify mechanisms that keep stem cells active until old age. As a representative of the sparsely investigated crustaceans and of animals with indeterminate growth and extended brood care the marbled crayfish may even contribute to evolutionary theories of ageing and longevity. Some relatives are recommended as substitutes for investigation of topics, for which the marbled crayfish is less suitable like genetics of ageing and achievement of life spans of decades under conditions of low food and low temperature. Research on ageing in the marbled crayfish and its relatives is of practical relevance for crustacean fisheries and aquaculture and may offer starting points for the development of novel anti-ageing interventions in humans."

Understanding the physical basis of human memory will enable therapies to both enhance youthful memory and reverse its decline with age. From ScienceDaily, an example of present investigations into the biology of memory: "We found one of the key proteins involved in the process of memory and learning. This protein is present in the part of the brain in which memories are stored. We have found that in order for any memory to be laid down this protein, called the M3-muscarinic receptor, has to be activated. We have also determined that this protein undergoes a very specific change during the formation of a memory - and that this change is an essential part of memory formation. In this regard our study reveals at least one of the molecular mechanisms that are operating in the brain when we form a memory and as such this represents a major break through in our understanding of how we lay down memories. This finding is not only interesting in its own right but has important clinical implications. One of the major symptoms of Alzheimer's disease is memory loss. Our study identifies one of the key processes involved in memory and learning and we state in the paper that drugs designed to target the protein identified in our study would be of benefit in treating Alzheimer's disease."

Another study to show that transplanting young ovaries into old mice extends life quite significantly: "successful ovarian transplants increased the lifespan of the mice by more than 40% ... All the mice in both experiments that had received transplants resumed the normal reproductive behaviour of young mice. They showed interest in male mice, mated and some had pups. Normally, old mice stay in the corner of the cage and don't move much, but the activity of mice that had had ovarian transplants was transformed into that of younger mice and they resumed quick movements. Furthermore, the lifespan of the mice who received young ovaries was much longer than that of the control mice: the mice that had received two ovaries lived for an average of 915 days, and the mice that had received one ovary, for an average of 877 days. The newest of our data show the life span of mice that received transplants of young ovaries was increased by more than 40%. ... The average normal lifespan for this particular breed of mice [is] 548 days. ... it was not known why the ovarian transplant increased the lifespan of the mice, but it might be because the transplants were prompting the continuation of normal hormonal functions."

Following on from a demonstration of decellularized rat lungs, another team has produced similar work: "Researchers have been able to create tiny mouse lungs in the lab that are able to breathe. The lungs were created with stem cells and attached to a ventilator. ... They used a technique called decellularization, similar to the method used to create a beating mouse heart in a different lab at the University of Minnesota in 2008. In the cancer center, they took a mouse lung and stripped away all its cells. Then, injected the natural framework with stem cells. At first they used fetal mouse lung cells, but this year they had another breakthrough using adult stem cells called 'induced pluriopotent stem cells.' ... That's basically a cell that we can take from anybody and re-program to act like an embryonic stem cell ... The hope is one day human lungs could be re-created for transplant with a greater chance of success. Right now, there is no tissue matching for lung transplants. ... The beauty of that is that you can then create a tissue for an organ that's transplantable that is derived from the patient and therefore would not be recognized as foreign by the immune system and not rejected. By adding the ventilator to make the lungs breathe, the stem cells are further trained to act like lung cells. It's a huge success considering lungs are such complicated organs with some 60 different kinds of cells."

A review paper: "Mitochondrial disorders can no longer be ignored in most medical disciplines. Such disorders include specific and widespread organ involvement, with tissue degeneration or tumor formation. Primary or secondary actors, mitochondrial dysfunctions also play a role in the aging process. Despite progresses made in identification of their molecular bases, nearly everything remains to be done as regards therapy. Research dealing with mitochondrial physiology and pathology has [greater than 20 years] of history around the world. We are involved, as are many other laboratories, in the challenge of finding ways to fight these diseases. However, our main limitation is the scarcety of animal models required for both understanding the molecular mechanisms underlying the diseases and evaluating therapeutic strategies. This is especially true for diseases due to mutations in mitochondrial DNA (mtDNA), since an authentic genetic model of mtDNA mutations is technically a very difficult task due to both the inability of manipulating the mitochondrial genome of living mammalian cells and to its multicopy nature. This has led researchers in the field to consider the prospect of gene therapy approaches that can roughly be divided into three groups: (1) import of wild-type copies or relevant sections of DNA or RNA into mitochondria, (2) manipulation of mitochondrial genetic content, and (3) rescue of a defect by expression of an engineered gene product from the nucleus (allotopic or xenotropic expression)."



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