Anti Aging Advancement

Another Anti Aging Advancement

Funded by the SENS Research Foundation and allied philanthropists, the researchers at the Spiegel Lab are working on the tools needed to build the means to remove glucosepane cross-links from aged tissue. Like clearancturn back timee of senescent cells, this is one of the more promising near-term approaches to rejuvenation therapies because it is just the single, narrow problem, rather an enormous range of compounds and mechanisms grouped into a category, as is the case for amyloids, lipofuscin, and other forms of damaging metabolic waste. It should be possible to develop and deploy working approaches to glucosepane cross-link breaking in a much shorter period of time, once the initial hurdles are overcome.

Persistent sugary cross-links form in the extracellular matrix as a side-effect of the normal operation of cellular metabolism. In humans the vast majority of lasting, problematic cross-links involve glucospane. These cross-links alter and corrode the structural properties of tissue, making bone and cartilage fragile, and producing loss of elasticity in skin and blood vessels. While all of these are bad, the loss of blood vessel elasticity is probably the most important of these consequences, as increased vascular stiffness with advancing age drives the progression of hypertension, cardiac hypertrophy, and fatal cardiovascular disease. The sooner the research community makes the leap to far greater funding and interest in cross-link breaking, the better. This requires better tools, such as those planned in this new research project.

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SENS Research Foundation (SRF) has launched a new research program focused on developing monoclonal antibodies against glucosepane. David A. Spiegel will be running the project in his laboratory, which focuses on developing new methods and molecules that will facilitate our understanding and treatment of human disease.

Glucosepane is the most prevalent crosslink found in collagen in people over 65 years of age, and its presence has been correlated to age-related tissue damage through various mechanisms. Understanding of glucosepane has been hampered by the molecule’s complex and sensitive chemical structure; it can only be isolated from human samples in minute quantities and in an impure form. To enable these advances in both basic and therapeutic science, the Spiegel laboratory has recently accomplished the first total synthesis of glucosepane.

The lab is now utilizing its novel synthetic glucosepane derivatives to generate the first monoclonal anti-glucosepane antibodies. Access to these antibodies would profoundly accelerate the goal of developing the first discrete, specific reagents for labeling, studying, and perhaps also cleaving glucosepane in vivo. Such tools have tremendous potential to help illuminate, and reverse, age-related damage as it occurs in human tissues.

This research has been made possible through the generous support of Michael Antonov and the Forever Healthy Foundation and its founder Michael Greve. The Forever Healthy Foundation is a private nonprofit initiative whose mission is to enable people to vastly extend their healthy lifespans and be part of the first generation to cure aging. In order to accelerate the development of therapies to bring aging under full medical control, the Forever Healthy Foundation directly supports cutting-edge research aimed at the molecular and cellular repair of damage caused by the aging process.

Link: http://www.sens.org/outreach/press-releases/srf-and-spiegel-lab-to-collaborate-on-antibodies-to-glucosepane

A Drug That Actually Reverses Ageing

A drug that actually reverses ageing

University of New South Wales researchers have made a discovery that could lead to a revolutionary drug that actually reverses ageing.  It improves DNA repair and could even help NASA get its astronauts to Mars.

In a paper published in Science today, the team identifies a critical step in the molecular process that allows cells to repair damaged DNA.

Their experiments in mice suggest a treatment is possible for DNA damage from ageing and radiation. It is so promising it has attracted the attention of NASA, which believes the treatment can help its Mars mission.

While our cells have an innate capability to repair DNA damage —  which happens every time we go out into the sun, for example — their ability to do this declines as we age.

The scientists identified that the metabolite NAD+, which is naturally present in every cell of our body.  It has a key role as a regulator in protein-to-protein interactions that control DNA repair.

Treating mice with a NAD+ precursor, or “booster,” called NMN improved their cells’ ability to repair DNA damage caused by radiation exposure or old age.

“The cells of the old mice were indistinguishable from the young mice, after just one week of treatment,” said lead author Professor David Sinclair of UNSW School of Medical Sciences and Harvard Medical School Boston.

Human trials of NMN therapy will begin within six months.

“This is the closest we are to a safe and effective anti-ageing drug that’s perhaps only three to five years away from being on the market if the trials go well,” says Sinclair, who maintains a lab at UNSW in Sydney.

What it means for astronauts, childhood cancer survivors, and the rest of us

The work has excited NASA, which is considering the challenge of keeping its astronauts healthy during a four-year mission to Mars.

Even on short missions, astronauts experience accelerated ageing from cosmic radiation, suffering from muscle weakness, memory loss and other symptoms when they return. On a trip to Mars, the situation would be far worse: five per cent of the astronauts’ cells would die and their chances of cancer would approach 100 per cent.

Professor Sinclair and his UNSW colleague Dr Lindsay Wu were winners in NASA’s iTech competition in December last year.

“We came in with a solution for a biological problem and it won the competition out of 300 entries,” Dr Wu says.

Cosmic radiation is not only an issue for astronauts. We’re all exposed to it aboard aircraft, with a London-Singapore-Melbourne flight roughly equivalent in radiation to a chest x-ray.

In theory, the same treatment could mitigate any effects of DNA damage for frequent flyers. The other group that could benefit from this work is survivors of childhood cancers.

Dr Wu says 96 percent of childhood cancer survivors suffer a chronic illness by age 45, including cardiovascular disease, Type 2 diabetes, Alzheimer’s disease, and cancers unrelated to the original cancer.

“All of this adds up to the fact they have accelerated ageing, which is devastating,” he says.

“It would be great to do something about that, and we believe we can with this molecule.”

An anti-ageing pill could be on the horizon

For the past four years, Professor Sinclair and Dr Wu have been working on making NMN into a drug substance with their companies MetroBiotech NSW and MetroBiotech International.

The human trials will begin this year at Brigham and Women’s Hospital, in Boston.

The findings on NAD+ and NMN add momentum to the exciting work the UNSW Laboratory for Ageing Research has done over the past four years.

They’ve been looking at the interplay of a number of proteins and molecules and their roles in the ageing process.

They had already established that NAD+ could be useful for treating various diseases of ageing, female infertility and also treating side effects of chemotherapy.

In 2003, Professor Sinclair made a link between the anti-ageing enzyme SIRT1 and resveratrol.  Which is a naturally occurring molecule found in tiny quantities in red wine.

While resveratrol activates SIRT1 alone, NAD+ boosters activate all seven sirtuins, SIRT1-7, and should have an even greater impact on health and longevity.

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Materials provided by University of New South Wales. Note: Content may be edited for style and length.

Journal Reference:

  1. Jun Li, Michael S. Bonkowski, Sébastien Moniot, Dapeng Zhang, Basil P. Hubbard, Alvin J. Y. Ling, Luis A. Rajman, Bo Qin, Zhenkun Lou, Vera Gorbunova, L. Aravind, Clemens Steegborn, David A. Sinclair. A conserved NAD binding pocket that regulates protein-protein interactions during aging. Science, 24 Mar 2017: Vol. 355, Issue 6331, pp. 1312-1317 DOI: 10.1126/science.aad8242