Nature comments on recent advances: "At the turn of the twentieth century, the promise of regenerating damaged tissue was so far-fetched that Thomas Hunt Morgan, despairing that his work on earthworms could ever be applied to humans, abandoned the field to study heredity instead. Though he won the Nobel Prize in 1933 for his work on the role of chromosomes in inheritance, if he lived today, the advances in regenerative medicine may have tempted him to reconsider. Three studies published this week show that introducing new cells into mice can replace diseased cells - whether hair, eye or heart - and help to restore the normal function of those cells. These proof-of-principle studies now have researchers setting their sights on clinical trials to see if the procedures could work in humans. ... You can grow cells in a Petri dish, but that's not regenerative medicine. You have to think about the biology of repair in a living system. ... Japanese researchers grew different types of hair on nude mice, using stem cells from normal mice and balding humans to recreate the follicles from which hair normally emerges. ... A second study using regenerative techniques helped to restore some vision to mice with congenital stationary night blindness, an inherited disease of the retina. ... [Researchers reprogrammed] cardiac fibroblasts into cardiomyocytes - the muscle cells of the heart that are permanently lost after a heart attack. The team used a retrovirus to deliver three transcription factors that induced the reprogramming in adult mice, and improved their cardiac function. ... These three papers are just the tip of the iceberg. By the time we grow old, doctors are going to look back and say, 'Can you believe people used to go bald, go blind or even have their leg cut off from vascular disease?' - and then the doctor will treat the problem with an injection of cells."

Link: http://www.nature.com/news/regenerative-medicine-repairs-mice-from-top-to-toe-1.10472

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Via EurekAlert!: "Daily physical exercise may reduce the risk of Alzheimer's disease, even in people over the age of 80 ... The study showed that not only exercise but also activities such as cooking, washing the dishes and cleaning are associated with a reduced risk of Alzheimer's disease. These results provide support for efforts to encourage physical activity in even very old people who might not be able to participate in formal exercise but can still benefit from a more active lifestyle. ... For the study, a group of 716 people with an average age of 82 wore an actigraph, a device that monitors activity, on their non-dominant wrist continuously for 10 days. All exercise and non-exercise was recorded. They also were given annual tests during the four-year study that measured memory and thinking abilities. During the study, 71 people developed Alzheimer's disease. ... The research found that people in the bottom 10 percent of daily physical activity were more than twice as likely to develop Alzheimer's disease as people in the top 10 percent of daily activity. The study also showed that those people in the bottom 10 percent of intensity of physical activity were almost three times as likely to develop Alzheimer's disease as people in the top 10 percent of intensity of physical activity."

Link: http://www.eurekalert.org/pub_releases/2012-04/aaon-gmd041012.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Via EurekAlert!: "Daily physical exercise may reduce the risk of Alzheimer's disease, even in people over the age of 80 ... The study showed that not only exercise but also activities such as cooking, washing the dishes and cleaning are associated with a reduced risk of Alzheimer's disease. These results provide support for efforts to encourage physical activity in even very old people who might not be able to participate in formal exercise but can still benefit from a more active lifestyle. ... For the study, a group of 716 people with an average age of 82 wore an actigraph, a device that monitors activity, on their non-dominant wrist continuously for 10 days. All exercise and non-exercise was recorded. They also were given annual tests during the four-year study that measured memory and thinking abilities. During the study, 71 people developed Alzheimer's disease. ... The research found that people in the bottom 10 percent of daily physical activity were more than twice as likely to develop Alzheimer's disease as people in the top 10 percent of daily activity. The study also showed that those people in the bottom 10 percent of intensity of physical activity were almost three times as likely to develop Alzheimer's disease as people in the top 10 percent of intensity of physical activity."

Link: http://www.eurekalert.org/pub_releases/2012-04/aaon-gmd041012.php

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers have been manipulating stem cells to cause hair follicles to form and hair to grow for a few years now. Consider this research from 2009, for example:

Professor Lin Sung-jan took 10 hair follicles from rodents and cultivated 8 to 10 million dermal papilla cells in vitro in 20 days. Using aggregates of between 3 and 5 million dermal papilla cells, he mixed these with rodent skin cells and transplanted them onto bare rodent skin, which sprouted hair.

Bald skin and haired skin have the same cell populations needed to grow hair, as it turns out, so this sort of cell-based approach has merit. The end of the story will likely be some form of cell signalling treatment to instruct cells already present in the body to form hairs in an area of skin rather than cell transplants - but transplants are first in line for development. The process is not exactly straightforward, unfortunately. Much like the tissue engineering of teeth, some form of guiding technology must be established to ensure that the cells grow as they should - without it, you end up with misshapen or broken structures.

On this subject, the work of a Japanese group on hair regeneration has been in the news of late, and they seem to have established a proof of principle for guiding correct hair growth. You'll find an open access paper and a couple of popular press items to choose from, complete with pictures of a hairless mouse sporting a patch of engineered hair:

Previously, Tsuji and colleagues had bioengineered follicles and hair shafts in the lab using epithelial and mesenchymal cells from mouse embryos. Until now, it was unclear whether these organized clusters of cells would make normal hair if inserted into mouse skin.

In the new work, the team transplanted a group of the engineered follicles into the skin on the backs of hairless mice. After about two weeks, hairs began to sprout. Under the microscope, the hair grown from the bioengineered mouse follicles resembled normal hair, scientists found. And the mouse follicles went through the normal cycle of growing hair, shedding and making new hair.

When researchers injected the region around the bioengineered follicle with acetylcholine, a drug that causes muscles to contract, the hairs perked up. This suggests that the transplanted follicles had integrated with surrounding muscle and nerves like normal hair follicles do.

Importantly, the researchers were able to ensure hair didn't become ingrown or point in the wrong direction by attaching a nylon thread to the engineered follicles and guiding the hair to grow outward.

That guide method doesn't sound very scalable - though given that there is a market for hair restoration techniques that involve moving follicles one by one, I could see it finding use in the clinic. But we can live without our hair and our vanity; a legion of far more serious and life-threatening degenerations accompany aging, and those are where our attention should be directed. The most important long-term effects of this particular line of research will, I think, be the application of the lessons learned to other areas of tissue engineering: guiding the regeneration of small complex structures, of which there are a great many in the body.

The results also mark a step forward in efforts to regenerate organs such as salivary glands that form in a process similar to hair early in their development.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

From Queen Mary, University of London, investigation of the mechanisms of periodontitis in aging: "New research [sheds] light on why gum disease can become more common with old age. The study, published in Nature Immunology, reveals that the deterioration in gum health which often occurs with increasing age is associated with a drop in the level of a chemical called Del-1. The researchers say that understanding more about Del-1 and its effects on the body's immune system could help in the treatment or prevention of serious gum disease. ... As people age they are more likely to suffer from inflammatory diseases, including gum disease. The new research investigated gum disease in young and old mice and found that an increase in gum disease in the older animals was accompanied by a drop in the level of Del-1. This protein is known to restrain the immune system by stopping white blood cells from sticking to and attacking mouth tissue. Mice that had no Del-1 developed severe gum disease and elevated bone loss and researchers found unusually high levels of white blood cells in the gum tissue. When they treated the gums of the mice with Del-1, the number of white blood cells dropped, and gum disease and bone loss were reduced. The researchers say their findings could be the basis for a new treatment or prevention of gum disease."

Link: http://www.qmul.ac.uk/media/news/items/smd/71770.html

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Researchers are not having as much success as they'd like in finding unambiguous associations between specific genes and human longevity - studies are turning up results, but few are similar between populations, indicating that the genetics of natural variations in longevity are probably very complex: "It has long been thought that related individuals share a familial predisposition to longevity, and for more than a century numerous studies have investigated the degree to which human longevity might be an inherited characteristic. Most studies of this type have reported small (?10%) to moderate (?30%) heritability of human longevity, amid differences in definitions of longevity, methods of measuring it, ascertaining individuals who demonstrate it, and in various behavioral and environmental settings. These methodological differences likely account for much of the variation in the resulting estimates of the heritability of longevity. ... We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related 'affected individuals', defined as those in the top quartile for both excess longevity (EL=observed lifespan - expected lifespan) and familial excess longevity (FEL=weighted average EL across all relatives). A whole-genome scan for genetic linkage was performed on this sample using a panel of 1100 microsatellite markers. A strongly suggestive peak was observed in the vicinity of D3S3547 on chromosome 3p24.1, at a point nearly identical to that reported recently by an independent team of researchers from Harvard Medical School (HMS). ... Corroboration of the linkage of exceptional longevity to 3p22-24 greatly strengthens the case that genes in this region affect variation in longevity and suggest, therefore, an important role in the regulation of human lifespan. Future efforts should include intensive study of the 3p22-24 region."

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323558/

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

There are many possible forms of therapy that either might be built or are presently being built atop of a greater knowledge of stem cells and cell biotechnologies. Cultured populations of stem cells can be let loose into the body to do their work, or existing cells can be directed to take action where they would normally stand aside, or tissues can be constructed for transplant, and many more variants upon these themes. As explained in a recent open access paper, stem cells can also stand duty as a method of delivering a therapy rather than being a form of therapy themselves: they can move around the body largely unhindered, and different types of stem cells have quite strong opinions as to which part of the body they would like to migrate towards. Given the right signals, stem cells can even be directed to quite specific locations - consider the way in which cells respond to injury, for example. This is but one of countless signals that cause stem cells to travel or take specific actions: a great deal of future medicine will be based on better understanding and control over stem cells in the body.

So let us say that you want to move a dose of a fragile therapeutic molecule into the brain, past the blood-brain barrier - and, further, to quite specific locations within the brain. Why not enlist stem cells to carry it in? Unfortunately it's not completely straightforward - stem cells have their own ideas as to where they would like to go, and if that isn't suited to the need at hand, then further improvement in control is needed. The basic concept still looks promising, however, even though early attempts are not achieving great results:

Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated A? peptides that are the major constituents of the senile plaques.

Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered.

...

Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.

The medicine of the 2040s may involve more cell therapies than any other area at the present pace: cells ordered around, changed in situ into augmented bioartifical machinery to conduct repairs or deliver compounds to needed locations, or even joined by artificial cells that carry out similar duties but more effectively. We are built of cells, so it makes some sense that our medical technology might eventually also be largely built of cells, act through cells, or otherwise be based on the direct control and repair of cells.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm