Longevity News

Genes That Let You Live Beyond 100

posted on June 29, 2010

Bill Andrews sent me an interesting article about life extension. Bill is CEO of Sierra Sciences, where they screen compounds for their effect on activating telomerase. You might remember that telomerase is the enzyme that regulates telomere length, and telomeres are the protective tips of your chromosomes that gradually shorten as your cells divide. Lengthening shortened telomeres appears to reestablish your youth and potentially let you live a lot longer.

Doing that is a bit tricky, but Sierra Sciences is making progress. A big part of the solution to aging is understanding our genes and influencing their activity. First, it’s necessary to identify the ones which affect aging.

This month, the New York Post and The Times of London published the article “Found: genes that let you live to 100,” detailing longevity research at Leiden University.

Leiden University had previously published research on the physiological differences between centenarians and the rest of the population, finding that centenarians metabolize fats and glucose differently than the general population; that their skin ages more slowly; and that they have a lower prevalence of heart disease, diabetes, and hypertension. They also appear to have genetic protection against the effects of smoking and poor diet habits.

Now, the group has analyzed the genomes of these centenarians and found a suite of genes that are statistically much more common in centenarians than in the general population. The hope is that these genes can be used as drug discovery targets, and that one or more drugs can be developed that will afford us all the same protection against disease and environmental damage that centenarians enjoy. The research itself is due to be published later this year.                        

Many other researchers are identifying aging-related genes as well. Michael Rose at the University of California at Irvine, for example, has already discovered what could be hundreds of them, with more on the way. Next step is developing drugs that tweak them. This step is underway as you read this.

Long Life,
David Kekich
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LATEST HEALTHY LIFE EXTENSION HEADLINES

CELL TRANSPLANTS FOR MACULAR DEGENERATION (June 25 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4784
From the MIT Technology Review: "Rats genetically engineered to lose their sight can be protected from blindness by injections of human neural stem cells. A startup in Palo Alto, CA, plans to use the positive results to file for approval from the U.S. Food and Drug Administration to begin human trials. The company is already testing the cells in children with a rare, fatal brain disorder called Batten's disease. The company's cells are isolated from human fetal tissue and then grown in culture. To determine whether these cells can protect against retinal degeneration, scientists studied rats that were genetically engineered to progressively lose their photoreceptors - cells in the retina that convert light into neural signals. These animals are commonly used to model macular degeneration and retinitis pigmentosa, two major causes of blindness that result from cell loss in the retina. Researchers injected about 100,000 cells into the animals' eyes when the rats were 21 days old. The cells migrate over time, forming a layer between the photoreceptors and a layer of tissue called the retinal pigment epithelium, cells which nourish and support the photoreceptors. The cells protected vision in the part of the retina in which they were implanted."

PROGRESS IN VIRAL CANCER THERAPY (June 24 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4783
Scientific American looks at the state of viral cancer therapies: "The adapted virus that immunized hundreds of millions of people against smallpox has now been enlisted in the war on cancer. Vaccinia poxvirus joins a herpes virus and a host of other pathogens on a growing list of engineered viruses entering late-stage human testing against cancer. After a decade of development of so-called oncolytic viruses, the newest strains hold the most promise yet. In a two-pronged attack, these viruses specifically target tumor cells while delivering a cargo of immune-boosting genes. In contrast, viruses that cause cancer, such as the human papillomavirus that is responsible for most cases of cervical cancer, disrupt a cell's genome, thereby triggering out-of-control growth. When the engineered viruses recognize and infect cancer cells, they replicate and sometimes destroy their hosts. Several of the viruses also release the gene for granulocyte-macrophage colony-stimulating factor (GM-CSF) an immune system protein. The GM-CSF attracts a swarm of white blood cells and other immune system operatives that mount a further attack on the tumor. The vaccinia virus has been developed by the biotechnology company Jennerex. Later this year, the company plans to launch a phase III clinical trial in advanced liver cancer patients, in which the virus will be added to standard antibody treatment."

THE RISKS THAT COME WITH EXCESS BODY FAT (June 23 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4781
Another reason why you really don't want to live a lifestyle that makes you overweight: "For individuals 65 years of age and older, obesity, excess body fat around the waist and gaining weight after the age of 50 are associated with an increased risk of diabetes. Adiposity [body fat] is a well-recognized risk factor for type 2 diabetes among young and middle-aged adults, however, the relationships between different measures of body composition and diabetes in older adults [65 years of age or older] are not well described. [researchers]  examined the relationship between measures of overall body fat, fat distribution, changes in these measures, and diabetes risk among 4,193 men and women 65 years of age and older. The researchers found that BMI at baseline, BMI at 50 years of age, weight, fat mass, waist circumference, waist-hip ratio, and waist-height ratio were all strongly related to the risk of diabetes. For each measure, there was a graded increase in the risk of diabetes with increasing quintiles of adiposity. Participants in the highest category of adiposity had an approximately 2- to 6-fold increased risk of developing diabetes compared with those in the lowest category."

INFLAMMATION, GENETICS, AND LONGEVITY (June 23 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4780
A review paper from Italian researchers who have been working on understanding inflammaging for a number of years: "Aging is an inexorable intrinsic process that affects all cells, tissues, organs and individuals.
Due to a diminished homeostasis and increased organism frailty, aging causes a reduction of the response to environmental stimuli and, in general, is associated to an increased predisposition to illness and death.
Actually, it is characterized by a state of reduced ability to maintain health and general homeodynamics of the organism. A large part of the aging phenotype is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status of aging, 'inflamm-aging'. It is strictly linked to immunosenescence, and on the whole they are the major contributory factors to the increased frequency of morbidity and mortality among elderly. Inflamm-aging is compatible with longevity; even if centenarians have an increased level of inflammatory mediators in comparison to old subjects and they are very frail, they also have high level of anti-inflammatory cytokines together with protective genotypes. Actually, data on case control studies performed in Italian centenarians suggest that a pro-inflammatory genotype is unfavorable to reach extreme longevity in good health and likely favors the onset of age-related diseases such as cardiovascular diseases and Alzheimer's disease."

LIFESTYLE AND AGING-RELATED BIOMARKERS (June 22 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4778
This should be an expected result: "Cellular aging is characterized by telomere shortening, which can lead to uncapping of chromosome ends (telomere dysfunction) and that activation of DNA damage responses. There is some evidence the DNA damage accumulates during human aging and that lifestyle factors contribute to the accumulation of DNA damage. Recent studies have identified a set of serum markers that are induced by telomere dysfunction and DNA damage and these markers showed an increased expression in blood during human aging. Here, we investigated the influence of lifestyle factors (such as exercise, smoking, body mass) on the aging associated expression of serum markers of DNA damage [in] comparison to other described markers of cellular aging (p16(INK4a) upregulation and telomere shortening) in human peripheral blood. The study shows that lifestyle factors have an age-independent impact on the expression level of biomarkers of DNA damage. Smoking and increased body mass indices were associated with elevated levels of biomarkers of DNA damage independent of the age of the individuals. In contrast, exercise was associated with an age-independent reduction in the expression of biomarkers of DNA damage in human blood. The expression of biomarkers of DNA damage correlated positively with p16(INK4a) expression and negatively with telomere length in peripheral blood T-lymphocytes. Together, these data provide experimental evidence that both aging and lifestyle impact on the accumulation of DNA damage during human aging."

THE OPEN LETTER ON BRAIN PRESERVATION (June 21 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4777
Every year something on the order of 50 million people die, and the fine structure of the brain that houses their minds is allowed to decay, destroying them forever. It does not have to be this way: the technology exists to plastinate and store the newly deceased, preserving the data of the mind until such time as medical technology can work a restoration. "The Open Letter on Brain Preservation seeks to raise awareness regarding the science, ethics and legality surrounding the emerging scientific process of chemical, whole-brain preservation. We, the undersigned, hereby publicly profess our human right to undergo a high-quality elective chemical brain preservation procedure immediately upon our physical death, and demand that such a procedure be made legal and accessible within the existing medical system in our countries of residence. We further demand that if medical evidence exists that an individual's brain is being substantially damaged by Alzheimer's, tumors, or other disease processes that elective brain preservation be available prior to that individual's natural death."

THERE WILL ALWAYS BE FOOLISH OBJECTIONS (June 21 2010) http://www.longevitymeme.org/news/vnl.cfm?id=4776

A Newsweek article runs through some of the standard foolish objections to greater human longevity. There is no change so beneficial that people will refrain from protesting it - it is human nature to be vehemently against a new idea before being grudgingly for it: "When we consider the problem of aging, and imagine that we might be able to cure it, that alternating current we feel consists of longings and dread. We are afraid of what we wish for; and most of our fears, like our hopes, have always cycled in us. Dreams of immortality have led to terrible nightmares of boredom ever since people began writing down their thoughts. What happens when we have real antiaging pills that pass the tests of clinical trials? As bioethicists have begun to note, this is a problem that would make all our bioethical debates to date look small. What are the bioethical problems that have exercised us in the last 10 or 20 years? Stem cells. Cloning. Gene therapy. The privacy of genetic information. Steroids. All these problems matter in themselves, but all of them would be subsumed in the transformations of society and human nature that would be wreaked by a significant success with the human life span. And then will come the option of changing the genome itself. We will add or subtract genes to lengthen our lives, until there is no going back, because no human beings alive (however long they may live) will ever be human in the same way again. If we are going to survive to enjoy a good portion of the future, our health and happiness depend on a great deal of luck. The trouble with immortality is endless." There is no objection to longevity that comes close to touching the present horror of aging - the more than 100,000 people who die each and every day.

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