Harvard scientists reverse the aging process in mice – now for humans

http://www.guardian.co.uk/science/2010/nov/28/scientists-reverse-ageing-mice-humans

Harvard scientists reverse the ageing process in mice – now for humans
Harvard scientists were surprised that they saw a dramatic reversal, not just a slowing down, of the ageing in mice. Now they believe they might be able to regenerate human organs


Ian Sample, science correspondent
guardian.co.uk, Sunday 28 November 2010 18.01 GMT


In mice, reactivating the enzyme telomerase led to the repair of damaged tissues and reversed the signs of ageing. Photograph: Robert F. Bukaty/AP
Scientists claim to be a step closer to reversing the ageing process after rejuvenating worn out organs in elderly mice. The experimental treatment developed by researchers at Harvard Medical School turned weak and feeble old mice into healthy animals by regenerating their aged bodies.

The surprise recovery of the animals has raised hopes among scientists that it may be possible to achieve a similar feat in humans – or at least to slow down the ageing process.

An anti-ageing therapy could have a dramatic impact on public health by reducing the burden of age-related health problems, such as dementia, stroke and heart disease, and prolonging the quality of life for an increasingly aged population.

"What we saw in these animals was not a slowing down or stabilisation of the ageing process. We saw a dramatic reversal – and that was unexpected," said Ronald DePinho, who led the study, which was published in the journal Nature.

"This could lead to strategies that enhance the regenerative potential of organs as individuals age and so increase their quality of life. Whether it serves to increase longevity is a question we are not yet in a position to answer."

The ageing process is poorly understood, but scientists know it is caused by many factors. Highly reactive particles called free radicals are made naturally in the body and cause damage to cells, while smoking, ultraviolet light and other environmental factors contribute to ageing.

The Harvard group focused on a process called telomere shortening. Most cells in the body contain 23 pairs of chromosomes, which carry our DNA. At the ends of each chromosome is a protective cap called a telomere. Each time a cell divides, the telomeres are snipped shorter, until eventually they stop working and the cell dies or goes into a suspended state called "senescence". The process is behind much of the wear and tear associated with ageing.

At Harvard, they bred genetically manipulated mice that lacked an enzyme called telomerase that stops telomeres getting shorter. Without the enzyme, the mice aged prematurely and suffered ailments, including a poor sense of smell, smaller brain size, infertility and damaged intestines and spleens. But when DePinho gave the mice injections to reactivate the enzyme, it repaired the damaged tissues and reversed the signs of ageing.

"These were severely aged animals, but after a month of treatment they showed a substantial restoration, including the growth of new neurons in their brains," said DePinho.

Repeating the trick in humans will be more difficult. Mice make telomerase throughout their lives, but the enzyme is switched off in adult humans, an evolutionary compromise that stops cells growing out of control and turning into cancer. Raising levels of telomerase in people might slow the ageing process, but it makes the risk of cancer soar.

DePinho said the treatment might be safe in humans if it were given periodically and only to younger people who do not have tiny clumps of cancer cells already living, unnoticed, in their bodies.

David Kipling, who studies ageing at Cardiff University, said: "The goal for human tissue 'rejuvenation' would be to remove senescent cells, or else compensate for the deleterious effects they have on tissues and organs. Although this is a fascinating study, it must be remembered that mice are not little men, particularly with regard to their telomeres, and it remains unclear whether a similar telomerase reactivation in adult humans would lead to the removal of senescent cells."

Lynne Cox, a biochemist at Oxford University, said the study was "extremely important" and "provides proof of principle that short-term treatment to restore telomerase in adults already showing age-related tissue degeneration can rejuvenate aged tissues and restore physiological function."

DePinho said none of Harvard's mice developed cancer after the treatment. The team is now investigating whether it extends the lifespan of mice or enables them to live healthier lives into old age.

Tom Kirkwood, director of the Institute for Ageing and Health at Newcastle University, said: "The key question is what might this mean for human therapies against age-related diseases? While there is some evidence that telomere erosion contributes to age-associated human pathology, it is surely not the only, or even dominant, cause, as it appears to be in mice engineered to lack telomerase. Furthermore, there is the ever-present anxiety that telomerase reactivation is a hallmark of most human cancers."

Merck cholesterol drug extremely effective in study

http://www.reuters.com/article/idUSN1719543320101117

Wed, Nov 17 2010
* Raises good HDL cholesterol 138 pct
* Cuts bad LDL cholesterol 40 pct in patients on statins
* No safety or torcetrapib-like problems observed
* 30,000-patient outcomes study to begin in 2011 Q2
By Bill Berkrot and Ransdell Pierson
NEW YORK/CHICAGO, Nov 17 (Reuters) - An experimental Merck & Co (MRK.N: Quote, Profile, Research, Stock Buzz) heart drug, from a class of medicine with a troubled past, appeared to be safe and had a "jaw dropping" effect on both good and bad cholesterol levels, according to data from a clinical trial.
Merck's anacetrapib increased good HDL levels by a stunning 138 percent after 24 weeks of treatment, and lowered levels of bad LDL cholesterol by 40 percent in patients already taking LDL-lowering statins, researchers said.
"The lipid effects are jaw dropping in both directions," said Dr. Christopher Cannon, the study's lead investigator from Brigham and Women's Hospital in Boston. He presented the data at the American Heart Association scientific meeting in Chicago on Wednesday.
Researchers found no anacetrapib safety issues during the 18-month study, and patients receiving the drug had fewer serious heart problems than those given a placebo.
Even if development of the medicine continues without a hitch, it will likely be at least five years before Merck can begin selling the drug.
Anacetrapib belongs to a class of drugs called CETP inhibitors that produced one of the most spectacular clinical failures in pharmaceutical history. A pivotal study of Pfizer Inc's (PFE.N: Quote, Profile, Research, Stock Buzz) highly touted torcetrapib was stopped in late 2006 after higher death rates were found among those taking the drug, pulling the plug on an $800 million Phase III program.
Based on the data from the anacetrapib trial, called Define, "we are 94 percent confident that anacetrapib doesn't have the clinical (side) effects of torcetrapib," Cannon said.
The HDL increase seen with anacetrapib "is double what torcetrapib does; it's four times what niacin can do if you can push niacin to its full 2 gram dose; and 10 times the effect seen with statins," Cannon said, comparing anacetrapib with other therapies.
It is believed that HDL has a heart protective effect, possibly by carrying LDL away from the arteries.
Anacetrapib also cut by 36 percent levels of LP(a), which is believed to be an independent cardiovascular risk factor.
The 1,623-patient, 18-month Define trial was designed to show anacetrapib does not have the unintended effects on blood chemistry and blood pressure found in detailed analyses of what went wrong with the Pfizer drug.
"It's been found that torcetrapib unfortunately as a molecule somehow lands itself in the adrenal gland and then pumps out aldosterone, other hormones, and has all these effects," Cannon explained.
Compared with the placebo group, patients receiving anacetrapib in the study showed no difference in electrolytes, aldosterone or blood pressure, and no other safety concerns were seen with the drug, he said.
"This trial was set up so that we would have some more reassurance that the drug was safe before doing a gigantic trial. And that's what we found, that it looks safe so far," Cannon said.
In the wake of torcetrapib, Merck has long known that to gain approval for anacetrapib, it will have to conduct a large so-called outcomes trial to prove its drug cuts heart attacks and death rather than just impacts cholesterol levels.
Plans for such a study were announced on Wednesday. It will include some 30,000 patients at high risk of heart attack or other serious heart problems, and take about four years to complete. Enrollment is expected to begin in the second quarter of 2011, researchers said.
Patients in the 18-month Define study all had coronary disease or were at high risk for heart disease, and were already taking a statin, such as Lipitor, to lower their LDL levels. They received either 100 milligrams of anacetrapib or a placebo once a day on top of their statin.
At the start of the study, patients on average had a baseline HDL of 40 and LDL of 81. Those on anacetrapib on average saw HDL leap to 101 and LDL drop to 45. HDL levels of placebo patients rose only to 46, while LDL fell to 77.
Patients whose LDL dropped below 25 were taken off the drug as a precaution, which was part of the study's design. "We didn't see any problems, but this gets the LDL down as low as its ever been in any study," Cannon said.
Researchers observed a trend toward lower rates of cardiovascular death, heart attack, stroke and hospitalization for unstable angina. The need for angioplasty or bypass surgery over 18 months was significantly lower on anacetrapib -- eight patients versus 28 on placebo.
While the dramatic impact on HDL is clear, it remains to be determined if raising it through the CETP inhibitor mechanism can save lives and hospitalizations.
Roche (ROG.VX: Quote, Profile, Research, Stock Buzz) and Japan Tobacco (2914.T: Quote, Profile, Research, Stock Buzz) are also forging ahead with development of a CETP inhibitor, called dalcetrapib.
"There is very real uncertainty as to what anacetrapib will do on clinical outcomes," said Rory Collins, co-director of the clinical trial service unit at the University of Oxford, who will lead the outcomes study program.
"It is incredibly exciting. It could be really the next big thing in cardiovascular disease," Collins said. (Reporting by Bill Berkrot and Randell Pierson; editing by John Wallace)

Researchers Grow a Liver in a Lab Setting

Researchers have created a buzz in the organ transplant world by growing a liver in a lab setting. However, this liver may function just like any other liver but it is miniature, a test to see if the technology was possible. The group used stem cells to create the liver which is said to be genetically identical to that of a human liver.
The idea that human organs can be grown in labs has been the stuff of science fiction novels for years. However, it has become a reality these days. Still, the researchers have said that it will be years before the technology and science are advanced far enough to create full size organs.
When the advancements are complete it will revolutionize the transplant world. Patients will no longer have to wait years for a new organ when one can be specifically grown for them in a lab setting.
One issue is the fact that these organs are designed by using stem cell research. This gives them a specific DNA structure that must be unique to the patient. Stem cell research has only recently restarted in the US after President Obama lifted a ban imposed by former President Bush.
Organ transplants are a hot commodity in this world today. Black markets buy and sell organs through underground medical facilities, often causing fatalities when the patients develop infections from unsterile conditions.
With the advancement of lab grown organs research may be able to save the lives of millions every year.

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