How to cure aging: One drug can extend life span

How to cure aging: One drug can extend life span

By Boonsri Dickinson | July 7, 2011, 9:44 AM PDT
Source: smartplanet.com

Scientists believe they’ve found a drug that can slow down premature aging in mice and could one day be used to extend human life. This is the story of a drug called rapamycin, nicknamed the forever young drug. The key chemical in this drug was discovered in the soil on the famed, remote Easter Island, reports Technology Review.

Previously, the drug’s wonderful fountain of youth effects were seen in only in invertebrates such as fruit flies, yeast and nematode worms, where it helped cells manufacture new proteins and kept bad cells at bay. But now, the scientists are seeing that it has similar effects on the aging process in mammals.

In the study published in Nature, scientists show that when rapamycin is administered to mice as a food supplement, it expands their life span. Now in human years, that would translate to an extra decade of a healthy living. The work was the result of three separate studies conducted at a number of institutions including Jackson Laboratory. The independent groups reported their results to the National Institute of Aging’s Interventions Testing Program, which aims to investigate which drugs might slow down aging in mice.

According to Technology Review:

“People who study the biology of aging feel that in order to deal with diseases of aging, it’s much more efficient to target underlying mechanisms, rather than focusing on heart disease or cancer or diabetes or Alzheimer’s or Parkinson’s separately,” says David Harrison, a researcher at Jackson Laboratory. “If we could alter underlying mechanisms of aging, all of these things would be postponed.”

The researchers think that the drug could target the same pathway that occurs when the body is put under a calorie restriction diet, a technique used for extending life. Calorie restriction dates back to 1934, after it became known that cutting calories extended the lifespan of rats.

However, it is not known just how effective this drug would be in humans, considering its known side effects of pneumonia and fungal infections. Still, scientists are more hopeful that it could be used to keep old age diseases under control. It could buy more time by simply slowing the progression of diseases such as Alzheimer’s and diabetes, resulting in a longer, healthy life span for humans the way it did in mice.

The wonder drug was previously used in children with the condition called Hutchinson-Gilford Progeria Syndrome, a rare condition that makes kids die of old age by the time they are only 12 years old. The condition is caused by a build up of protein in cells in the body. The drug cleans the cells of this toxic protein, and has been approved by the FDA. It’s used to suppress the immune system in patients who just had organ transplants.

Scientists will need to figure how to get around of some of the drug’s side effects like pneumonia, before other applications of this anti-aging drug has legs. It’s not like healthy people who want to live forever will be taking this regularly.

On a fundamental level, the drug gets rid of the junk that harms cells. The drug cleans out the waste from cells and organs, Dimitri Krainc, told The Telegraph. Using it to get the waste management system into gear would extend the life of our cells and organs, and keep us healthier as a result.

The famous gerontologist Aubrey de Grey thinks we can actually “cure” aging by preventing molecular and cellular damage before it spins out of control. De Grey tells Reuters that, ““if we could do that in the case of certain modified forms of cholesterol which accumulate in cells of the artery wall, then we simply would not get cardiovascular disease.” In other words, try to stop cellular damage before it becomes pathogenic and we can live for a long time.

De Grey is featured in an upcoming documentary, named How to Live Forever. The trailer looks pretty good. I’m looking forward to seeing a screening of it this weekend. Leave me a comment if you want me to ask De Grey any questions:

First Drug Shown to Extend Life Span in Mammals [Technology Review]

Photo: NASA image by Earth Observatory

First Gene Therapy Successful Against Aging-Associated Decline: Mouse Lifespan Extended Up to 24% With a Single Treatment

First Gene Therapy Successful Against Aging-Associated Decline: Mouse Lifespan Extended Up to 24% With a Single Treatment

May 14, 2012 — A new study consisting of inducing cells to express telomerase, the enzyme which -- metaphorically -- slows down the biological clock -- was successful. The research provides a "proof-of-principle" that this "feasible and safe" approach can effectively "improve health span." (Source: sciencedaily.com)

Pictured are Maria A. Blasco and

Bruno M. Bernardes de Jesús (co-author)

in the CNIO building in Madrid. (Credit: CNIO)

A number of studies have shown that it is possible to lengthen the average life of individuals of many species, including mammals, by acting on specific genes. To date, however, this has meant altering the animals' genes permanently from the embryonic stage -- an approach impracticable in humans. Researchers at the Spanish National Cancer Research Centre (CNIO), led by its director María Blasco, have demonstrated that the mouse lifespan can be extended by the application in adult life of a single treatment acting directly on the animal's genes. And they have done so using gene therapy, a strategy never before employed to combat aging. The therapy has been found to be safe and effective in mice.

The results were recently published in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with Eduard Ayuso and Fátima Bosch of the Centre of Animal Biotechnology and Gene Therapy at the Universitat Autònoma de Barcelona (UAB), treated adult (one-­‐year-­‐old) and aged (two-­‐year-­‐old) mice, with the gene therapy delivering a "rejuvenating" effect in both cases, according to the authors.

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. The therapy, furthermore, produced an appreciable improvement in the animals' health, delaying the onset of age-­‐related diseases -- like osteoporosis and insulin resistance -- and achieving improved readings on aging indicators like neuromuscular coordination.

The gene therapy consisted of treating the animals with a DNA-­modified virus, the viral genes having been replaced by those of the telomerase enzyme, with a key role in aging. Telomerase repairs the extreme ends or tips of chromosomes, known as telomeres, and in doing so slows the cell's and therefore the body's biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

This study "shows that it is possible to develop a telomerase-­based anti-­aging gene therapy without increasing the incidence of cancer," the authors affirm. "Aged organisms accumulate damage in their DNA due to telomere shortening, [this study] finds that a gene therapy based on telomerase production can repair or delay this kind of damage," they add.

'Resetting' the biological clock

Telomeres are the caps that protect the end of chromosomes, but they cannot do so indefinitely: each time the cell divides the telomeres get shorter, until they are so short that they lose all functionality. The cell, as a result, stops dividing and ages or dies. Telomerase gets around this by preventing telomeres from shortening or even rebuilding them. What it does, in essence, is stop or reset the cell's biological clock.

But in most cells the telomerase gene is only active before birth; the cells of an adult organism, with few exceptions, have no telomerase. The exceptions in question are adult stem cells and cancer cells, which divide limitlessly and are therefore immortal -- in fact several studies have shown that telomerase expression is the key to the immortality of tumour cells.

It is precisely this risk of promoting tumour development that has set back the investigation of telomerase-­‐based anti-­‐aging therapies.

In 2007, Blasco's group demonstrated that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and, also, extra copies of cancer-­‐resistant genes. These animals live 40% longer than is normal and do not develop cancer.

The mice subjected to the gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult so do not have time to accumulate sufficient number of aberrant divisions for tumours to appear.

Also important is the kind of virus employed to carry the telomerase gene to the cells. The authors selected demonstrably safe viruses that have been successfully used in gene therapy treatment of hemophilia and eye disease. Specifically, they are non-­‐replicating viruses derived from others that are non-­‐pathogenic in humans.

This study is viewed primarily as "a proof-­‐of-­‐principle that telomerase gene therapy is a feasible and generally safe approach to improve healthspan and treat disorders associated with short telomeres," state Virginia Boccardi (Second University of Naples) and Utz Herbig (New Jersey Medical School-­‐University Hospital Cancer Centre) in a commentary published in the same journal.

Although this therapy may not find application as an anti-­‐aging treatment in humans, in the short term at least, it could open up a new treatment option for ailments linked with the presence in tissue of abnormally short telomeres, as in some cases of human pulmonary fibrosis.

More healthy years

As Blasco says, "aging is not currently regarded as a disease, but researchers tend increasingly to view it as the common origin of conditions like insulin resistance or cardiovascular disease, whose incidence rises with age. In treating cell aging, we could prevent these diseases."

With regard to the therapy under testing, Bosch explains: "Because the vector we use expresses the target gene (telomerase) over a long period, we were able to apply a single treatment. This might be the only practical solution for an anti-­‐aging therapy, since other strategies would require the drug to be administered over the patient's lifetime, multiplying the risk of adverse effects."