Advances in Life Extension

This story is way below the radar as far as the press is involved, but the sheer number of separate routes tells us that work on the topic is hot and heavy. Most of this work is been done with mice in order to establish protocols.

In the meantime, of way more practical impact is the recent work I reported on two days ago with the use of naringenin to reset the liver’s function to eliminate obesity once and for all. Obviously if such a protocol could restore an individual to a non obese state and properly restore liver metabolism, then a substantial improvement in lifespan should naturally accrue. This will be available in the necessary mega doses just as quickly as someone can synthesize naringenin or concentrate it from perhaps grapefruit peels or something. Trust me on this one, the gold rush is on as we write.

I will not try to cover this field of research completely, but we should see the odd item as this all develops. Perhaps Next Big Future can keep a good handle on this one as I expect everyone cares about this issue.

What is clearly opening up is real time gene therapy and the wondrous thing there is that the simple obvious mechanisms happen to work. It was no trick at all forty years ago to conjecture that a virus could be used to deliver a therapy. That it actually works without a hitch is like winning a lottery. Thus researchers are getting very brave and beginning to simply try things out. This means that we can brace for a flood of interesting results in this field, not unlike the flood associated with cancer research as simple protocols were applied broadly.

August 24, 2009

Life Extending Gene Therapy Progress and Rundown of Life Extension Demonstrated In Mice that Could Apply to Humans

http://nextbigfuture.com/2009/08/life-extending-gene-therapy-progress.html

A new study from the University of Missouri may shed light on how to increase the level and quality of activity in the elderly.

In the study, published in this week's edition of Public Library of Science – One, MU researchers found that gene therapy with a proven "longevity" gene energized mice during exercise, and might be applicable to humans in the future.

Mice would live longer when their genome was altered to carry a gene known as mitochondria-targeted catalase gene, or MCAT. However, such approaches would not be applicable to human. Duan and Dejia Li, a post-doctoral researcher working with Duan, took a different approach and placed the MCAT gene inside a benign virus and injected the virus into the mice.

Once injected, Duan and Li tested the mice and found that they could run farther, faster and longer than mice of the same age and sex. Duan attributes this performance enhancement to the MCAT and believes the gene is responsible for removing toxic substances, known as free radicals, from the mitochondria, the powerhouse of the cell. By using this specific gene therapy vector, the virus, to introduce the longevity gene, Duan and Li opened the possibility of human treatment.

This work is number 6 on a list assembled at Fighting Aging. Note: Fighting aging has a lot more details and links for each item.

Twelve Life Extension Techniques Demonstrated in Mice

Fighting Aging has a rundown of life extension techniques demonstrated in Mice.Twelve of the most interesting methods I've seen in past years. Note: omitting a number of studies that show only small (less than 10%) increases in maximum mouse life span, and also leaving out some work in progress that looks likely to enhance life span.

1) Calorie Restriction, Intermittent Fasting, and Methionine Restriction

Imposition of calorie restriction in mice has been shown to extend life span by around 40% even when initiated comparatively late in life.

2) Growth Hormone Knockout, IGF-1 and Insulin Signalling Manipulation

A breed of dwarf mouse that entirely lacks growth hormone is the present winner of the Mprize for longevity, living 60-70% longer than the compeition's standard laboratory mouse species. This is primarily interesting as a demonstration that insulin signalling and IGF-1 - intimately bound up with growth hormone - are very important to the operations of metabolism that determine life span. These dwarf mice are not very robust: whilst healthy and active, they wouldn't survive outside the laboratory or without good care due to their low body temperature.

3) Telomerase Plus p53

A Spanish group published a study in 2008 showing 50% life extension in mice by a suitable combination of enhanced telomerase and p53.

4) Inactivating the CLK-1 Gene

Reducing the activity of the mitochondria-associated gene clk-1 - lowering the amount of protein generated from its blueprint in other words - boosts mouse longevity by 30% or so.5) SkQ, a Mitochondrially Targeted Ingested Antioxidant

A Russian researcher has demonstrated a form of antioxidant that can be targeted to the mitochondria even though ingested. Per the mitochondrial free radical theory of aging, anything that can reduce the damage mitochondria do to themselves via the free radicals they generate in the course of their operation should extend life span. Indeed, SkQ seems to boost mouse life span by about 30%:

6) Genetic Manipulation to Target Catalase to the Mitochondria

A couple of research groups have shown that through either gene therapy or genetic engineering the levels of a naturally produced antioxidant catalase can be increased in the mitochondria. The mice lived 20 percent longer than normal mice.

7) Genetic deletion of pregnancy-associated plasma protein A (PAPP-A)

This is another method of reducing cancer incidence and also extending life span by 30% or so, but this time seemingly through manipulation of the insulin signalling system in a more subtle way than previous growth hormone knockout studies. The end results certainly look like a win-win situation: extended life span and less cancer with no downside.

8) Knockout of the adenylyl cyclase type 5 (AC5) gene

Mice lacking the gene for the AC5 protein, which strangely enough appears to be a crucial component of the opioid response in mammals in addition to its other roles, live 30% longer. This is suggested to be due to a more aggressive, effective repair and prevention response to oxidative damage.

9) Metformin used as a calorie restriction mimetic drug

The drug metformin has been demonstrated to act in some ways like calorie restriction in mouse biochemistry, producing a modest 10% gain in maximum life span.

10) FIRKO, or fat-specific insulin receptor knock-out mice

FIRKO mice have less visceral body fat than normal mice, even while eating at the same calorie levels. They live a little less than 20% longer, and this is taken as one line of evidence to show that that possessing a lot of visceral fat is not good for longevity.

11) Removal of visceral fat by surgery

Continuing the fat theme, researchers demonstrated last year that you can extend the life span of mice by surgically removing excess visceral fat. It doesn't extend life as much as calorie restriction, but it is significant

12) Overexpression of PEPCK-C, or phosphoenolpyruvate carboxykinase

In this case, researchers have no firm conclusion as to why and how this genetic manipulation works. As in a number of other cases, this investigation wasn't started as a part of any aging or longevity study, and the longevity of these mice is a fortunate happenstance. Nonetheless, here we have a case of what appears to be a more than 50% life extension - though note that the formal life span study has not been published, so you might assume the comments below to refer to the outliers amongst these mice rather than the average.

Stem Cell Advance for Diabetes

When stem cell therapy first arrived, it looked like the maiden’s prayer for sufferers of diabetics. Mother Nature was just not that accommodating. It has taken all this time to begin to see real progress on a number of stem cell fronts and only lately has the news began to land thick and fast.

Here we have a stem cell based therapy that actually delays substantially the onset of type 1 diabetes. Not a cure but still a major win.

I suspect every family has been touched by diabetes. This has become epidemic , not just because of eating abuse but also we are all living that extra ten years denied our parents. Just quitting smoking is allowing a huge number of folks to experience the joys of diabetes.

Actually solving this disease will have a huge repercussion throughout the health system.

I suspect that just as 90% of men at sixty and 90% of women at seventy have heart disease, they are also incipient diabetics and need to fend it of.

Apr 14, 2009

Diabetics insulin-free after stem-cell transplants

http://www.sciam.com/blog/60-second-science/post.cfm?id=diabetics-insulin-free-after-stem-c-2009-04-14&sc=CAT_HLTH_20090414

Patients recently diagnosed with type 1diabetes who received transplants of their own immune stem cells were able to go without insulin injections for nearly five years after the procedure, scientists report today.

In type 1 diabetes, the immune system attacks islet cells in the pancreas that the body depends on to make insulin, a hormone that converts glucose into energy. Treatment typically includes injections or infusions of insulin. Now, research in the new Journal of the American Medical Association shows that the transplant technique — autologous nonmyeloablative hematopoietic stem cell transplantation, in which a patient is infused with immune system stem cells from his or her own blood — enabled 20 of 23 recipients to thrive without insulin injections for up to 58 months. Twelve were able to stay off insulin continuously, while the rest had to periodically receive treatment.

The scientists, from Northwestern University Feinberg School of Medicine and the School of Medicine of Ribeirao Preto in Sao Paulo, Brazil, reported in 2007 that the transplant patients were able to stay insulin-free for as long as a year and a half. At that time, critics wondered if the effect was genuine or reflected a kind of "honeymoon period" following the procedure.

The new research measured levels of C-peptides, a protein made by the same islet cells that manufacture insulin and that's considered a marker of the hormone. Two to three years after the transplants, patients had markedly higher C-peptide levels, suggesting that the transplant had effectively "re-set" their immune systems not to attack their islet cells, study co-author Richard Burt, chief of the division of immunotherapy at Northwestern, tells ScientificAmerican.com. Their ability to stay off insulin, he says, is "clearly an effect of the cells recovering and producing insulin, not just some honeymoon period or diet or exercise."

The procedure would likely work only within three months of patients being diagnosed with type 1 diabetes, before their immune systems have destroyed all of their insulin-producing islet cells, Burt says. The next step is proving that the technique — which Burt says could cost up to $90,000 — works in a randomized controlled trial.

Because patients were transplanted with their own cells, they didn’t have to take anti-rejection drugs that other transplant recipients are prescribed to prevent them from reacting new cells. Side effects of the transplant included temporary hair loss, nausea, fever and sterility in some of the patients who had already gone through puberty. (Patients ages 13-31 and mostly male underwent transplants.) Younger patients who undergo the transplants in the future might be told to bank their sperm as a precaution, Burt says.

Scientists are also studying whether islet-cell transplants would effectively treat diabetes. That procedure would involve infusing a patient with a deceased donor's islet cells. Because those cells would come from another person, islet cell transplantation would require recipients to take anti-rejection drugs.