Partial Reversal of Aging Achieved in Laboratory

During the past 100 years, Mankind has achieved many of its age-old dreams: conquering dreadful diseases, achieving spaceflight and escaping the stubborn grasp of Earth, walking on the Moon, diving to the very deepest depths of the world’s mighty oceans…

Now another milestone has been reached: the first real breakthrough in reversing the aging process—a leap forward that may one day eliminate death as it is known.

Pioneer Harvard Medical School professor Ronald A. DePinho and his research team have announced a dramatic step-forward in Man’s battle against old age. DiPinho is the director of Dana-Farber’s Belfer Institute for Applied Cancer Science. Working with DePinho on the report is first author is Mariela Jaskelioff, a research fellow in medicine in DePinho’s laboratory.

Some have called aging a disease endemic to the planet, others a disorder in the way DNA replicates—a breakdown of the process caused by genetic defects magnified over a lifetime—or the end result of the environment itself driven by a “dirty sun” that continuously bathes the Earth with age-inducing radiation.

The journal Nature has just published a report, in advance of their print issue, declaring that DePinho—senior author of the report—succeeded in engineering mice with controllable a telomerase gene utlizing enzymatic reactions. The enzyme protects the telomeres (little protective terminals) that provide protective caps at the ends of chromosomes.

How it works

Past investigations have revealed that as animals (including humans) age, telomerase drop off to lower levels. That has been linked to ongoing erosion of the telomeres. This progressive deterioration leads to massive tissue degeneration, a weakening of the auto-immune system, loss of physical functionality, malfunctioning of the body’s systems including organs and an increasing inability for DNA to replicate itself correctly at the cellular level.

The net result of all that malfunctioning is what is termed “aging.”

Now, by providing a telomerase switching device in the form an an enzyme within mice, the Harvard team were able to artificially age mice in the laboratory. With the switch installed, the team could now test if turning the enzyme back “on” would stop or even reverse the aging process.

“We wanted to know: If you could flip the telomerase switch on and restore telomeres in animals with entrenched age-related disease, what would happen?” DePinho said. “Would it slow down aging, stabilize it, or even reverse it?”

After they “flipped the switch” reactivating the enzyme the mice astoundingly began to grow younger instead of older. Muscle mass, circulatory systems, respiration, functionality—even reversal of brain disease and infertility—occurred.

The process was benign. No animal showed any signs of stress, confusion or—more importantly—developing cancers. Past research has shown that cancer turns on telomerase to circumvent the aging process. In a human body afflicted with cancer, the only cells that are immortal are cancer cells.

The experimental team induced premature aging in the mice by engineering them to suffer pronounced tissue and DNA damage. The experimental mice all had drastically shortened, malfunctioning telomeres that worsened during successive generations. Organs were adversely affected, as well as cell replication and brain functions.

The crucial part of the experiment arrived when the researchers activated the telomerase gene. According to the Harvard press release:

“Rather than supply the rodents with supplemental telomerase, the scientists devised a way to switch on the animals’ own dormant telomerase gene, known as TERT. They engineered the endogenous TERT gene to encode a fusion protein of TERT and the estrogen receptor. This fusion protein would only become activated with a special form of estrogen. With this setup, scientists could give the mice an estrogen-like drug at any time to stimulate the TERT-estrogen receptor fusion protein and make it active to maintain telomeres.

“Against this backdrop, the researchers administered the estrogen drug to some of the mice via a time-release pellet inserted under the skin. Other animals, the controls, were given a pellet containing no active drug.

“After four weeks, the scientists observed remarkable signs of rejuvenation in the treated mice. Overall, the mice exhibited increased levels of telomerase and lengthened telomeres, biological changes indicative of cells returning to a growth state with reversal of tissue degeneration, and increase in size of the spleen, testes, and brain.”

About the amazing results, DePinho notes: “It was akin to a Ponce de León effect.” The Spanish explorer, Ponce de León, spent a lifetime seeking the legendary and elusive “Fountain of Youth.”

Potential applications

Although at the moment the breakthrough has only been with mice, applications will undoubtedly be created for humans—significantly affecting human lifespans and quality of life—in the future.

Other than extension of the human lifespan, applications of the bio-technology may include treating rare genetic disorders and people suffering from premature aging.

“Whether this would impact on normal aging is a more difficult question,” DiPinho stated. “But it is notable that telomere loss is associated with age-associated disorders and thus restoration of telomeres could alleviate such decline.”

The results provide new insight into the aging process and give researchers a new tool in unlocking the secrets to age-regression techniques. DePinho said that the process might create new methods for treating regenerative diseases especially in the field of adult stem cell gene therapy.

“If you can remove the underlying damage and stresses that drive the aging process and cause stem cells to go into growth arrest, you may be able to recruit them back into a regenerative response to rejuvenate tissues and maintain health in the aged,” he explained.

Nature’s article concludes with the authors of the report asserting, “This unprecedented reversal of age-related decline in the central nervous system and other organs vital to adult mammalian health justifies exploration of telomere rejuvenation strategies for age-associated diseases.”

So, once Mankind escapes old age and death, can the elimination of taxes be far behind?

Sources / Links

“Partial reversal of aging achieved in mice” Harvard Gazette

Harvard website

Ronald A. DePinho [File photo by Kris Snibbe/Harvard Staff Photographer]

Caption to photo: “Researchers led by Ronald A. DePinho (above), a Harvard Medical School professor of genetics, say their work shows for the first time a dramatic reversal of many aspects of age-related degeneration in mice, a milestone in aging science achieved by engineering mice with a controllable telomerase gene. The projection of chromosomes seen here shows telomeres (highlighted in red) on their ends.”