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Firefly protein lights up degenerating muscles, aiding muscular-dystrophy research, scientists show

BY BRUCE GOLDMAN

Stanford University School of Medicine scientists have created a mouse model of muscular dystrophy in which degenerating muscle tissue gives off visible light.

The observed luminescence occurs only in damaged muscle tissue and in direct proportion to cumulative damage sustained in that tissue, permitting precise monitoring of the disease’s progress in the mice, the researchers say.

While this technique cannot be used in humans, it paves the way to quicker, cheaper and more accurate assessment of the efficacy of therapeutic drugs. The new mouse strain is already being employed to test stem cell and gene therapy approaches for muscular dystrophies, as well as drug candidates now in clinical trials, said Thomas Rando, MD, PhD, professor of neurology and neurological sciences and director of Stanford’s Glenn Laboratories for the Biology of Aging.

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Rando Videocast: Is aging reversible? : resetting the clock

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NIH Director’s Wednesday Afternoon Lecture Series: The Annual Florence Mahoney Lecture

Aging is a process that is generally viewed as unidirectional, relentless, and inevitable. However, in addition to the existence of non-aging species, or at least species with negligible senescence, data from a wide range of living organisms suggests that environmental influences can markedly slow and even halt the aging process. Furthermore, recent experimental evidence suggests that aspects of the molecular and functional characteristics of aged cells and tissues even in mammals can be restored to a more youthful state. Analyses of age-related changes in cells have revealed clear epigenetic changes, and the reversibility of some of those processes, in essence leading to cell and tissue rejuvenation, suggest epigenetic mechanisms.

Current studies focus on understanding the nature and regulation of those epigenetic mechanisms and the extent to which the aging clock can be rewound or reset by defined environmental influences while leaving other cellular characteristics, such as their state of differentiation, intact.

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Rando Podcast: Regenerative Medicine Today #111

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Regenerative Medicine Today welcomes Thomas Rando, MD, PhD. 

Dr. Rando discusses his research in muscle stem cell biology as well as his role in the upcoming Regenerative Rehabilitation Symposium in Pittsburgh.

Scientists trigger muscle stem cells to divide

Thomas Rando

BY KRISTA CONGER

A tiny piece of RNA plays a key role in determining when muscle stem cells from mice activate and start to divide, according to researchers at the Stanford University School of Medicine. The finding may help scientists learn how to prepare human muscle stem cells for use in therapies for conditions such as muscular dystrophy and aging by controlling their activation state.

It’s the first time that a small regulatory RNA, called a microRNA, has been implicated in the maintenance of the adult stem cell resting, or quiescent, state.

“Although on the surface the quiescent state seems to be relatively static, it’s quite actively maintained,” said Thomas Rando, MD, PhD, professor of neurology and neurological sciences. “We’ve found that changing the levels of just one specific microRNA in resting muscle stem cells, however, causes them to spring into action.”

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5 Questions: Rando on resetting the ‘aging clock,’ cell by cell

Thomas Rando

Advances in the study of stem cells have fueled hopes that someday, via regenerative medicine, doctors could restore aging people’s hearts, livers, brains and other organs and tissues to a more youthful state. A key to reaching this goal — to be able to provide stem cells that will differentiate into other types of cells a patient needs — appears to lie in understanding “epigenetics,” which involves chemical marks stapled onto DNA and its surrounding protein husk by specialized enzyme complexes inside a cell’s nucleus. These markings produce long-lasting changes in genes’ activity levels within the cell — locking genes into an “on” or “off” position. Epigenetic processes enable cells to remain true to type (a neuron, for instance, never suddenly morphs into a fat cell) even though all our cells, regardless of type, share the same genetic code. But epigenetic processes also appear to play a critical role in reducing cells’ vitality as they age.

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Huge VA project to boost med school mission

A new $54 million mental health center is part of a $1-billion-plus renewal project under way at the Veterans Affairs Palo Alto Health Care System and its flagship campus on Miranda Avenue.

BY JONATHAN RABINOVITZ

A dozen state-of the-art buildings that will advance the medical school’s clinical, educational and research missions are beginning to rise, but Stanford isn’t leading the effort.

With a construction budget of more than $1 billion, the Veterans Affairs Palo Alto Health Care System, or VAPAHCS, has launched an ambitious building project on its flagship campus on Miranda Avenue in Palo Alto, leaving almost no spot of the 93-acre site untouched. The plan includes a new mental health center; the Department of Veterans Affairs’ largest rehabilitation center, which will combine polytrauma and blind rehabilitation; additional research space; and additional lodging facilities for veteran patients and family members.

The project is driven by an emphasis on patient-centric care and concerns about seismic safety. The project is also part of a broader shift by the VA and health care in general toward more outpatient services, concentrating the most advanced tertiary care services at flagship facilities, such as the Palo Alto site. VAPAHCS, in addition to revamping and expanding its outpatient facilities outside the Palo Alto campus, is taking steps to ensure that its main campus continues to offer the latest treatment modalities and meet new and pressing needs, such as those of the increasing numbers of veterans who have suffered multiple injuries, including traumatic brain injury. As part of that process, VAPAHCS is enhancing its 50-year affiliation with the School of Medicine, adding space for the education of Stanford doctors who treat veterans and the research by Stanford faculty on injuries and illness that affect veterans and others.

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Rando Video – Aspen Ideas Festival: ‘Can We Reverse Aging? Science and Mythology Behind Growing Old’

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No one likes to develop arthritis and more wrinkles. However, it’s a fact of life that we all grow old, and always will…Or is it? Cutting-edge studies indicating that old cells and tissues can be “rejuvenated” prompt us to question the timeless theory that aging is unavoidable.

Dr. Rando was an invited speaker at the Aspen Ideas Festival, where he gave a talk titled ‘Can We Reverse Aging? Science and Mythology Behind Growing Old’.

New center for research on aging established with grant from Glenn Foundation

Thomas Rando

BY RUTHANN RICHTER

The Glenn Foundation for Medical Research has awarded a $5 million grant to Stanford University to launch a new center on the biology of aging, focusing on the role of stem cells in the aging process.

At the new Paul F. Glenn Laboratories for the Biology of Aging at Stanford, researchers at the Stanford University School of Medicine will look at how stem cells change as an individual ages and how that contributes to the development of age-related diseases and disorders.

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Rando Video: Stanford Mini Med School presentation titled ‘Longevity and Aging in Humans’

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Thomas Rando and Anne Brunet provide a general overview on the process and potential prevention of aging. The topics they cover vary from symptoms of aging to unusual characteristics that seem to prolong longevity.

Stanford Mini Med School is a series arranged and directed by Stanford’s School of Medicine and presented by the Stanford Continuing Studies program. 

Rando Videocast: Interview with TSN

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Dr. Rando was an invited speaker at the Keystone Symposia on Molecular and Cellular Biology for Diet, Metabolism and Aging held in Tahoe City, California. He sat down for this interview with The Science Network.

 

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Thomas Rando

Thomas Rando

Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences, is one of two recipients of the 2008 Breakthroughs in Gerontology Award sponsored by the Glenn Foundation for Medical Research and the American Federation for Aging Research. The award provides $200,000 for a small number of pilot research programs that may be of relatively high risk but which offer significant promise of yielding transforming discoveries in the fundamental biology of aging. Rando will investigate how stem cells are able to divide throughout the life of an individual to give rise to new stem cells in tissue, such as new skin cells or cells in the blood, without acquiring mutations in their DNA and causing cancer. Read more

Stanford Researchers Find Culprit In Aging Muscles That Heal Poorly

By Louis Bergeron

STANFORD, Calif. — Communication is critical. Garbled in, garbled out, so to (mis-)speak. Workers who get incomplete instructions produce an incomplete product, and that’s exactly what happens with the stem cells in our aging muscles, according to researchers from the Stanford University School of Medicine.

Their study found that, as we age, the lines of communication to the stem cells of our muscles deteriorate and, without the full instructions, it takes longer for injured muscles to heal. Even then, the repairs aren’t as good. But now that the researchers have uncovered the conduit that conveys the work orders to muscle stem cells, that knowledge could open the door to new therapies for injuries in a host of different tissues.

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Adult Stem Cells May Have Smarts To Guard Against Cancer, Stanford Researchers Find

The findings, from the lab of Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences, suggest stem cells are careful when they undergo cell division so that random mutations in their chromosomes are not passed on to the next generation of stem cells. The results support a much-debated hypothesis proposed in 1975 by Oxford University geneticist John Cairns, PhD. Although other groups have uncovered hints that Cairns was right, Rando’s findings are the most detailed to date.

The results are published in the April 17 issue of the Public Library of Science-Biology.
Rando said no other work he’s done has created as much excitement among his colleagues in the stem cell field. “The lesson from this is that when something seems strange, don’t ignore it. Sometimes what puzzles you turns out to be the most interesting,” he said.

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Gene Therapy For Muscular Dystrophy Fixes Frail Muscle Cells In Animal Model, Stanford Study Finds

STANFORD, Calif. — A new gene therapy technique that has shown promise in skin disease and hemophilia might one day be useful for treating muscular dystrophy, according to a new study by researchers at Stanford University School of Medicine.

In the study, published online in the Proceedings of the National Academy of Sciences the week of Jan. 2, the researchers used gene therapy to introduce a healthy copy of the gene dystrophin into mice with a condition that mimics muscular dystrophy. The dystrophin gene is mutated and as a result produces a defective protein in the roughly 20,000 people in the United States with the most common form of the disease.

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Three New Pioneers: Scientists Receive Top NIH Award

BY LOUIS BERGERON

Three School of Medicine scientists, including one jointly appointed with the School of Engineering, are among a select group of 13 researchers nationwide being recognized for their innovative work by the National Institutes of Health. The winners of the NIH Director’s 2005 Pioneer Awards will each receive up to $500,000 annually for five years to help fund their research.

With three winners, Stanford has more awardees this year than any other institution. The NIH announced the winners on Sept. 29. “Although the Pioneer Award is relatively new, it has quickly become one of the most prestigious and important recognitions by the NIH,” said Philip Pizzo, MD, dean of the School of Medicine. “Having three Pioneer Award winners is simply remarkable.”

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Young Blood Revives Aging Muscles, Stanford Researchers Find

STANFORD – Any older person can attest that aging muscles don’t heal like young ones. But it turns out that’s not the muscle’s fault. A study in the Feb. 17 issue of Nature shows that it’s old blood that keeps the muscles down.

The study, led by Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences at the Stanford University School of Medicine, built on previous work showing that old muscles have the capacity to repair themselves but fail to do so. Rando and his group studied specialized cells called satellite cells, the muscle stem cells, that dot muscle tissue. These normally lie dormant but come to the rescue in response to damaged muscle-at least they do in young mice and humans.

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Age-Related Muscle Loss Linked To Protein Interplay, Says Stanford Researcher

Any older athlete can attest that aging muscles don’t heal as fast as youthful ones. Now researchers at Stanford University School of Medicine have found a molecular link between older muscles and slow healing. This work could lead to ways of preventing atrophy from immobilization, space flight or simply due to aging.

“What you really want to do is maintain the youthfulness of the regeneration pathway,” said Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences and an investigator at the Veterans Affairs Palo Alto Health Care System. The work will be published in the Nov. 28 issue of Science.

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