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Category: life extension – Page 499

A CRISPR Gene Therapy for Hutchinson-Gilford Progeria

Researchers at the Salk Institute have moved a step closer to a possible therapy for Hutchinson-Gilford progeria syndrome, a rare genetic disorder that is often described as accelerated aging, as people with it appear to age far faster than normal. Using a new CRISPR/Cas9 gene therapy in a mouse model, they were able to slow down the pace of the condition, improve health, and increase lifespan.

What is Hutchinson-Gilford progeria?

Progeria is a degenerative disorder caused by a mutation in the LMNA gene. This disease has an early onset and progresses rapidly, and animals and humans with progeria show symptoms that are similar to regular aging, only on a much-accelerated timescale, giving them drastically shorter lifespans than normal. Humans with this condition rarely live very long, with the average being only 13 years old.

We are happy to announce Dr. Laura Niedernhofer and Dr. Paul Robbins, University of Minnesota, as speakers for the 2019 Undoing Aging Conference

“Paul and Laura have made huge contributions to the biomedical gerontology field in recent years. Their work focuses on the characterisation and alleviation of the aspects of aging that are driven by DNA damage. At UA2019, their talks will describe their recent advances in the mechanistic understanding of DNA damage, aided by spectacularly good mouse models, and also their identification of natural products with potent senolytic activity”, says Aubrey de Grey.

undoing-aging.org/…/dr-laura-niedernhofer-and-dr-paul-robbi…

Single-dose CRISPR–Cas9 therapy extends lifespan of mice with Hutchinson–Gilford progeria syndrome

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.

Slowing the Aging Process

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.”

Experimental Anti-Aging Treatment That Kills Old Cells Has Passed First Human Trial

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.”

The Man Who Would Stop Time

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.

A new CRISPR/Cas9 therapy can suppress aging

LA JOLLA—(February 18, 2019) Aging is a leading risk factor for a number of debilitating conditions, including heart disease, cancer and Alzheimer’s disease, to name a few. This makes the need for anti-aging therapies all the more urgent. Now, Salk Institute researchers have developed a new gene therapy to help decelerate the aging process.

The findings, published on February 18, 2019 in the journal Nature Medicine, highlight a novel CRISPR/Cas9 genome-editing that can suppress the accelerated aging observed in mice with Hutchinson-Gilford progeria syndrome, a rare genetic disorder that also afflicts humans. This treatment provides important insight into the molecular pathways involved in accelerated aging, as well as how to reduce toxic proteins via .

“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,” says Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory and senior author of the paper. “Progeria is an ideal aging model because it allows us to devise an intervention, refine it and test it again quickly.”

Excessive Cell Size Contributes to Senescence

In a new study [1], researchers have identified the reason why cells become defective when they grow too large and why protein creation fails when cells grow larger than their original healthy size, as is typically seen in aged and senescent cells.

They demonstrate that in enlarged yeast and human cells, RNA and protein biosynthesis does not scale in proportion to the additional cell size, which then leads to a dilution of the cytoplasm. This phenomenon is also present in senescent cells, which display similar traits to those of large cells.

The research team concludes that the maintenance of a cell type-specific DNA-to-cytoplasm ratio is essential for the majority of cellular functions, and when cellular growth changes this ratio, it encourages cells to become senescent.

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