This article is reprinted by permission from NextAvenue.org.
The basics of heart health have been drilled into our brains: Eat less saturated fat. Keep moving. Know your “numbers” for cholesterol, blood pressure and BMI.
But what about that brain itself? Although life expectancy has more than doubled since 1900, our “mindspan” — how long we stay cognitively healthy — hasn’t kept pace.
In an extraordinary milestone procedure, scientists in the UK have performed the first gene therapy operation aimed at stopping progression of the most common cause of vision loss. The success of the procedure is yet to be determined, however the scientists suggest this one-off operation could be performed early in the degeneration process and essentially halt the disease in its tracks.
Autologous induced pluripotent stem cells (iPSCs) constitute an unlimited cell source for patient-specific cell-based organ repair strategies. However, their generation and subsequent differentiation into specific cells or tissues entail cell line-specific manufacturing challenges and form a lengthy process that precludes acute treatment modalities. These shortcomings could be overcome by using prefabricated allogeneic cell or tissue products, but the vigorous immune response against histo-incompatible cells has prevented the successful implementation of this approach. Here we show that both mouse and human iPSCs lose their immunogenicity when major histocompatibility complex (MHC) class I and II genes are inactivated and CD47 is over-expressed. These hypoimmunogenic iPSCs retain their pluripotent stem cell potential and differentiation capacity. Endothelial cells, smooth muscle cells, and cardiomyocytes derived from hypoimmunogenic mouse or human iPSCs reliably evade immune rejection in fully MHC-mismatched allogeneic recipients and survive long-term without the use of immunosuppression. These findings suggest that hypoimmunogenic cell grafts can be engineered for universal transplantation.
Hutchinson–Gilford progeria syndrome (HGPS) is a rare lethal genetic disorder characterized by symptoms reminiscent of accelerated aging. The major underlying genetic cause is a substitution mutation in the gene coding for lamin A, causing the production of a toxic isoform called progerin. Here we show that reduction of lamin A/progerin by a single-dose systemic administration of adeno-associated virus-delivered CRISPR–Cas9 components suppresses HGPS in a mouse model.
It’s inevitable in life, but aging isn’t really something people look forward to. Researchers have been seeking ways to reduce the impact of aging, not only because of vanity but also because as we age, there is a greater risk of certain serious health conditions like cancer, heart disease and neurodegenerative conditions like Alzheimer’s disease. Salk Institute scientists have now used CRISPR/Cas9, the gene-editing tool, to slow down aging. The work, reported in Nature Medicine, showed accelerated aging can be slowed in mice modeling a rare genetic disorder called Hutchinson-Gilford progeria syndrome.
“Aging is a complex process in which cells start to lose their functionality, so it is critical for us to find effective ways to study the molecular drivers of aging,” said the senior author of the report Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory. “Progeria is an ideal aging model because it allows us to devise an intervention, refine it and test it again quickly.”
“We were able to show that there is only a single type of microglia in the brain that exist in multiple flavours,” says project head Prof. Dr. Marco Prinz, medical director of the Institute of Neuropathology at the Medical Center — University of Freiburg. “These immune cells are very versatile all-rounders, not specialists, as has been the textbook opinion up to now,” sums up Prof. Prinz.
A team of researchers under the direction of the Medical Center — University of Freiburg has created an entirely new map of the brain’s own immune system in humans and mice. The scientists succeeded in demonstrating for the first time ever that the phagocytes in the brain, the so-called microglia, all have the same core signature but adopt in different ways depending on their function. It was previously assumed that these are different types of microglia. The discovery, made by means of a new, high-resolution method for analyzing single cells, is important for the understanding of brain diseases. Furthermore, the researchers from Freiburg, Göttingen, Berlin, Bochum, Essen, and Ghent (Belgium) demonstrated in detail how the human immune system in the brain changes in the course of multiple sclerosis (MS), which is significant for future therapeutic approaches. The study was published on 14. February 2019 in the journal Nature.
Not all damaged cells die. Some stick around as senescent cells, unable to divide but still able to produce chemical signals — and they could play a major role in the battle against aging.
“It is thought that these cells and the substances they produce are involved in the process of aging,” longevity researcher Nicolas Musi from the University of Texas at Austin told MIT Technology Review.
“The idea is that removing these cells may be beneficial to promote healthy aging and also to prevent diseases of aging.”
Circa 2011
Bill Andrews’s feet are so large, he tells me, that back when he was 20 he was able to break the Southern California barefoot-waterskiing distance record the first time he put skin to water. Then he got ambitious and went for the world speed record. When the towrope broke at 80 mph, he says, “they pulled me out of the water on a stretcher.”
The soles of the size-15 New Balances that today shelter those impressive feet strike a steady clap-clap on the macadam as Andrews and I lope down a path along the Truckee River that takes us away from the clutter of cut-rate casino hotels, strip malls and highway exit ramps that is downtown Reno, Nevada. Andrews, 59, is a lean 6-foot-3 and wears a close-cropped salt-and-pepper Vandyke and, for today’s outing, a silver running jacket, nicely completing a package that suggests a Right Stuff–era astronaut. He is in fact one of the better ultramarathoners in America. I am an out-of-shape former occasional runner, so it gives me pause to listen as Andrews describes his racing exploits. “I can run 100 miles, finish, turn around, and meet friends of mine on the course who are still coming in,” he says. “I’ve been in many races where I’m stepping over bodies of people who have collapsed, and I’m feeling great.”
“I want to cure my aging, my friends’ and family’s aging, my investors’ aging, and I want to make a ton of money,” Andrews says. His return to running after a middle-aged break was, he says, inspired by a revelation he had at a time when he and a small team of scientists at his biotech start-up, Sierra Sciences, had been working 14 to 18 hours a day in the lab for five years, rather obsessively pursuing a particular breakthrough. Finally, his doctor told him he was headed for an early grave. “I thought, god, I don’t want to cure aging and then drop dead,” Andrews says.
Researchers from Texas A&M University, led by Dr. Akhilesh K. Gaharwar, have developed a new way to deliver treatment for cartilage regeneration.
Gaharwar, assistant professor in the Department of Biomedical Engineering at Texas A&M, said the nanoclay-based platform for sustained and prolonged delivery of protein therapeutics has the potential to impact treating osteoarthritis, a degenerative disease that affects nearly 27 million Americans and is caused by breakdown of cartilage that can lead to damage of the underlying bone.
As America’s population ages, the number of osteoarthritis incidences is likely to increase. One of the greatest challenges with treating osteoarthritis and subsequent joint damage is repairing the damaged tissue, especially as cartilage tissue is difficult to regenerate.
