Healthy Life Extension

Funding Aging Research


posted on November 15th, 2011

Dear Future Centenarian,

A new, potentially disruptive stem-cell technology, has been announced. Its implications? To intervene in the aging process.
Researchers at the Mayo Clinic in Rochester, MN, found they could essentially freeze certain aspects of the aging process in an adult mammal by using a drug to target and destroy senescent cells. 

Shirley S. Wang™s article titled œCell Study Finds a Way to Slow the Ravages of Age recently appeared in the Wall Street Journal.

Here are some excerpts from the article:

Scientists may have found a way to put off some conditions of aging, according to a study in which they postponed or even prevented such afflictions as cataracts and wrinkle-inducing fat in mice.
For the first time, scientists showed in mice that removing a type of aging cell from the body that has stopped dividing”can delay or prevent age-related health issues.

Most young healthy cells divide continuously in order to keep body tissues and organs functioning properly, but eventually stop splitting,­ a state called senescence, ­and are replaced by others. Senescence occurs throughout life, but people's ability to clear such cells from their bodies decreases with age, leading to a buildup.

"If you could clear senescent cells, you perhaps could treat age-related diseases as a group rather than individually," said Jan van Deursen, senior author of the paper and a professor in the departments of biochemistry and pediatric and adolescent medicine at Mayo.

The importance of cell senescence to the aging process has long been suspected. But the latest finding demonstrates definitively that these cells play a role in age-related conditions, according to Felipe Sierra, director of the division of aging biology at the National Institute on Aging, who wasn't involved in the study.

When cells become senescent, they produce harmful compounds such as those that cause inflammation. Chronic tissue inflammation with aging is thought to underlie dementia, atherosclerosis and diabetes, among other ills, according to James Kirkland, head of Mayo's Center on Aging, who was also an author of the study.

Senescent cells make up only a small portion of cells, some 5 percent or less,­ in the tissue of elderly people, but their effects can be widespread.

Because senescence is believed to have developed as a defense against cancer, in which cells divide uncontrollably, simply halting the process could be dangerous.

But scientists have wondered for decades if the damage inflicted by senescent cells could be stopped if they were removed from the body altogether, or if the harmful substances they produced were neutralized.

The team treated mice with a drug that identifies cells that have stopped dividing. The drug then initiates the natural process that leads to cell death by puncturing the membranes of those cells alone.

The researchers found a "quite dramatic delay" in the development of cataracts and age-related changes to muscle and fat, Dr. van Deursen said.

In other mice, the compound was administered in old age. Clearance of senescent cells in those mice prevented further deterioration.

The drug appeared to clear out only senescent cells, not normal ones, and the animals didn't appear to suffer any side effects, the researcher said.

Here™s a link to a dramatic video. Both mice are seven months old. The decrepit old mouse in front is frail, hunchbacked, and skinny secondary to muscle atrophy. The mouse in back has a youthful appearance following administration of a drug to clear senescent cells.

Long Life,
David Kekich


BUILDING STRONG MICE AND WORMS Friday, November 11, 2011
Via EurekAlert!: researchers "created super strong, marathon mice and nematodes by reducing the function of a natural inhibitor, suggesting treatments for age-related or genetically caused muscle degeneration are within reach. It turns out that a tiny inhibitor may be responsible for how strong and powerful our muscles can be. By acting on a receptor (NCoR1), [researchers] were able to modulate the transcription of certain genes, creating a strain of mighty mice whose muscles were twice a strong as those of normal mice.

By genetically manipulating the offspring of [mice and nematodes], the researchers were able to suppress the NCoR1 corepressor, which normally acts to inhibit the buildup of muscle tissues. In the absence of the inhibitor, the muscle tissue developed much more effectively. The mice with the mutation became true marathoners, capable of running faster and longer before showing any signs of fatigue. In fact, they were able to cover almost twice the distance run by mice that hadn't received the treatment. They also exhibited better cold tolerance. Unlike previous experiments with so-called super mice, this study addresses the way energy is burned in the muscle and the way the muscle is built. Examination under a microscope confirmed that the muscle fibers of the modified mice are denser, the muscles are more massive, and the cells in the tissue contain higher numbers of mitochondria - cellular organelles that deliver energy to the muscles. Similar results were also observed in nematode worms, allowing the scientists to conclude that their results could be applicable to a large range of living creatures."

AN INTERVIEW WITH MICHAEL RAE Friday, November 11, 2011
Michael Rae is the co-author of Ending Aging, a research assistant at the SENS Foundation, and a long-standing figure of note in the calorie restriction community: "I would say that one exciting recent development is that, with an increase in our research budget this year (based on performance last year and a more optimistic financial outlook from many of our donors), we've recently approved funding for several quite important and exciting research projects. One is a project whose ultimate aim is to tissue engineer a new thymus. The thymus is a gland located near the breast bone, where T-cells (an important immune cell) mature. The thymus shrinks with age, and the tissues on the outer layer of the organ where T-cells mature lose their architectural integrity, leading to a progressive failure to produce new T-cells to fight novel infections.

The thymus engineering project, which is underway with SENS Foundation support at the Wake Forest University Institute for Regenerative Medicine by Dr. John Jackson and colleagues, is to use a trick that you may have heard of having been used to make a new rat heart using the tissue scaffolding of another's. The fifth SENS Conference was, indeed, quite amazing! Unlike the previous conference, this time much more of the work being presented had already been published; it was none the less remarkable to see just how much had been accomplished in the last year, from restoring cognitive function in a mouse model of Alzheimer's disease using a drug that boosted up the ability of their brains' lysosomes ('garbage disposal systems' as it were) to break down the sticky beta-amyloid protein [to] a just-begun study on a very bold and ambitious way [to] restore the loss of cells and degraded circuitry of the aging neocortex (the area of the brain where, arguably, our highest, most 'human' cognitive activity occurs)."

A good demonstration of the state of the art of tissue engineering: "Last spring, a research team at Japan's RIKEN Center for Developmental Biology created retina-like structures from cultured mouse embryonic stem cells. This week, the same group reports that it's achieved an even more complicated feat - synthesizing a stem-cell-derived pituitary gland. The pituitary gland is a small organ at the base of the brain that produces many important hormones and is a key part of the body's endocrine system. It's especially crucial during early development, so the ability to simulate its formation in the lab could help researchers better understand how these developmental processes work.

The experiment wouldn't have been possible without a three-dimensional cell culture. The pituitary gland is an independent organ, but it can't develop without chemical signals from the hypothalamus, the brain region that sits just above it. With a three-dimensional culture, the researchers could grow both types of tissue together, allowing the stem cells to self-assemble into a mouse pituitary. Using this method, we could mimic the early mouse development more smoothly, since the embryo develops in 3-D in vivo. Fluorescence staining showed that the cultured pituitary tissue expressed the appropriate biomarkers and secreted the right hormones. The researchers went a step further and tested the functionality of their synthesized organs by transplanting them into mice with pituitary deficits. The transplants were a success, restoring levels of glucocorticoid hormones in the blood and reversing behavioral symptoms, such as lethargy."

Tengion is one of the research groups attempting to tissue engineer replacement sections of intestine: "Tengion has demonstrated that smooth muscle cells seeded on its biological scaffolding and then implanted in rodents exhibit functional regeneration of both the inner lining of epithelial cells and the surrounding layers of small intestine smooth muscle cells in as little as eight weeks post-implantation. The regeneration of small intestine from smooth muscle cells using our technology platform represents an important step forward in the development of functional, regenerated organs. Our goal is to translate preclinical data and proof of concept findings into clinical programs that could represent a broad range of medical treatment possibilities for patients in need of new bladders, kidneys and other organs. In this preclinical study, patch and tubular constructs were implanted in rodent small intestines and histologically evaluated for evidence of regeneration of the neo-mucosa and muscle layers. In as little as eight weeks post-implantation, laminarly organized neo-mucosa and muscle layer bundles were demonstrated, supporting the approach of using autologous smooth muscle cells and biomaterial combination products to spur regeneration of the small intestine. Patients with short bowel syndrome have typically undergone extensive small intestine resectioning and may become dependent on parenteral nutrition, a costly treatment associated with multiple complications, and could potentially benefit from a regenerative medicine approach."

News of more incremental progress towards a cell transplant therapy to treat Parkinson's: "Parkinson's disease takes hold as cells that produce dopamine die off in part of the brain called the substantia nigra. This causes tremors, rigidity and slowness of movement, though patients may also experience tiredness, pain, depression and constipation, which worsen as the disease progresses. Brain cells that die off in Parkinson's disease have been grown from stem cells and grafted into monkeys' brains in a major step towards new treatments for the condition.

US researchers say they have overcome previous difficulties in coaxing human embryonic stem cells to become the neurons killed by the disease. Tests showed the cells survive and function normally in animals and reverse movement problems caused by Parkinson's in monkeys. The breakthrough raises the prospect of transplanting freshly grown dopamine-producing cells into human patients to treat the disease. Previously we did not fully understand the particular signals needed to tell stem cells how to differentiate into the right type of cells. The cells we produced in the past would produce some dopamine but in fact were not quite the right type of cell, so there were limited improvements in the animals. Now we know how to do it right, which is promising for future clinical use."

Back to Top