The genes that could one day increase lifespan in humans

     After ten years of research by the Buck Institute for Research on Aging and the University of Washington has identified 238 genes that increase the replicative lifespan of S. cerevisiae yeast cells when removed.  This was the first time 189 of these genes were linked to aging.  The results found could provide new genomic target that could improve human health.

     Dr. Matt Kaeberlein, PhD from the Department of Pathology at the University of Washington and his team began the painstaking process of counting and examining 4700 yeast strains of yeast each with a single gene deletion.  Each strain had the daughter cell and mother cells separated and count to see how many times the mother cell divided. 

     The effort produced the information about how different genes and their pathways modulate aging in yeast. The deletion of gene LOS1, which helps relocate transfer RNA that brings amino acid to ribosomes to build proteins, produced huge results. LOS1 is influenced by a master switch the is associated with caloric restriction and increase lifespan, mTOR; also LOS1 influences another gene Gcn4 that helps govern DNA damage control.
     This research is only part of the process to map the relationship between the gene pathways that govern aging.  A number of these age-extending genes are found in roundworms and humans alike so the deletion of these genes could also prolong the lives of human eventually.  The researchers hope that this research will produce new therapies.
    "Almost half of the genes we found that affect aging are conserved in mammals," said Dr. Kennedy. "In theory, any of these factors could be therapeutic targets to extend healthspan. What we have to do now is figure which ones are amenable to targeting."(1)
      I am a little afraid of this to come true.  I couldn't think about what would happen if more humans were able to extend their lives.  How many people would like to extend their lifespan if they had any of disease or a disability that would affect how they live. Imagine if you were able to live to be over 100 but you happened to lose the use of your legs at later in your life; would you want to live longer if your quality of life starts to decline.

http://www.sciencedaily.com/releases/2015/10/151008142230.htm
http://www.buckinstitute.org/

1. Buck Institute for Research on Aging. "Mapping the genes that increase lifespan: Comprehensive study finds 238 genes that affect aging in yeast cells." ScienceDaily. ScienceDaily, 8 October 2015. <www.sciencedaily.com/releases/2015/10/151008142230.htm>.

Longer Life Span?

     Nobody wants to die, living a longer life is a goal that most people have. People have tried many many things to try to live a longer life, with not much success. Dr. Ajit, a researcher at the University of California may be on to something. His research has uncovered a gene that may be linked to a longer lifespan. This gene (CD33rSIGLEC) is involved anti inflammation. Dr Ajit's research as proven that mice with less copies of this gene show signs of early aging and death. This research is the first of its kind that links a specific gene to living longer, although this is still the beginning of  this research it is looking promising.


     Inflammation is a natural process of the bodies immune system, it is completely normal for the body to respond to infection or tissue damage with swelling. However, chronic inflammation can be a hazard to the body, such  as arthritis, or celiac disease. Having inflammation for long periods of time can destroy tissues and cause premature aging. With this information it makes sense that having a gene that codes against inflammation would cause you to live longer. The issue that arose in this research is that they have yet to find out if this gene is linked to a longer life, or if mammals would develop more of this gene because they were living longer. There is still research to be done on this topic but I believe that these scientists are on the right track.


Article: A Longer Life May Lie in Number of Anti-Inflammatory Genes
Article 2: More Anti-inflammatory Genes Mean Longer Lifespans for Mammals

Italian Scientists Link Gene to Longer Life

A team of Italian scientists made an amazing discovery in the genetics of longevity in mice. The discovery's effects is unknown in humans but it could lead to the drugs that postpone the effects of aging.

Oxygen creates many byproducts within the body that can corrode our bodies cells. To battle the corruption of cells and DNA the cells are "programmed" to self destruct before the damage becomes too great and the damaged cells become cancerous cells. The team has studied the gene that makes a protein that triggers the "self-destruct" process in those cells in their response to too much oxygen damage, mice that lacked the trigger protein lived thirty percent longer than normal, with no apparent side effects.

Although the mice were genetically unable to self destruct their damaged cells, they are presumably living longer because they are no longer being zapped by the self destruct mechanism even though they are genetically suffering oxygen damage.

Dr. Pelicci says that the trigger protein belongs to a class of proteins in which many inhibitory drugs are known and it shouldn't be to difficult to create a drug to block the trigger.

Phenotype modification occurs when the expression of one gene alters the expression of another gene. Gene modifiers can cause enhanced phenotypes or reduced phenotypes, and in this case it would be living longer in mice and hopefully drugs that postpone aging in humans.

Caloric restriction is already known to benefit life span in mice and creating a drug that mimics the effects of caloric restriction without the hassle and pain would be extremely valuable.

The downside of caloric restriction in mice however is the reduced fertility, but the fertility of the mice with the blocked trigger protein appears to be normal, but Dr. Pelicci is skeptical that the fertility effect of the blocked trigger protein is too mild to have been detected yet.



Article Link: http://www.nytimes.com/1999/11/18/us/scientists-link-a-single-gene-to-longer-life-in-mice.html
Secondary Link:Modifier Genes in Mice and Humans

Favorable CETP Variant Can Signify A Longer Life

        A new study found that people with a particular gene variant, in the gene CETP, may survive the longest. CETP, cholesteryl ester transfer protein, is located on chromosome 16. It is a plasma protein that facilitates the transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins. HDL is known as the "good" kind of cholesterol, and an increase in the blood levels of HDL is caused by the favorable variant of the CETP gene.  

        For a long time, researchers knew that people with this gene variant have a better chance at living longer than 95, and sometimes even 100, years. A new study, presented by Dr. Sofiya Milman, shows that when comparing elderly people above the age of 95, the people with the advantageous variant of the CETP gene outlive the other elderly people. This study expands on the work began at Einstein College of Medicine in New York City in the 1990s. When describing the centenarians she has studied, Milman says, "They don't only live longer, they live healthier too."
        Before conducting the study Milman was aware that the CETP variant was found to be related to decreased rates of heart disease and strokes and sharper mental function. Milman conducted the study by gathering 400 ninety-seven year old New York residents and following them for about one to eleven years. The researchers found evidence confirming that people with the favorable CETP variant and higher HDL levels lived longer.

 

        CETP and HDL are not the only keys to a long life. Exercise, healthy eating, and adequate sleep are still some very important aspects to a long and healthy life. Understanding CETP, HDL, and other "longevity" genes are still important and may open many doors in the research world. "Down the road, it might be possible to develop therapies that mimic these genes' effects," Milman believes.

        This article stood out to me because the subject of long life is really interesting to me. As a child, I always believed that researchers would eventually invent a "magic potion" that caused everybody to live forever. Hearing there is a gene that effects one's life span and that drug companies have already started working on CETP inhibitors, makes my childhood assumption sound closer than ever. Now that I think about everybody living forever, it might not actually be a good thing. Overpopulation would be an extreme concern and resources would diminish even quicker. This article is still very fascinating and makes me wonder if I could possibly have the favorable CETP variant.

Main Article:  http://medicalxpress.com/news/2014-11-longevity-gene-key-life.html
Related Article: http://www.sciencedaily.com/releases/2010/01/100112165234.htm

Sequencing Genomes to Live Longer

Andrew Pollack's article in The New York Times on March 4, 2014, discussed the large goals of Dr. J Craig Venter. Dr. Venter is a wealthy entrepreneur who wants to use the sequencing of genomes in order for people to live longer lives. He began Human Longevity, a company that will be processing 40,000 human genomes a year. He hopes that by using these genome sequences, and other parts of a person's DNA, he can learn more about age related diseases and how to prevent or cure them. His original company, Synthetic Genomics, develops new genomic based solutions for global problems. Dr. Venter claims to have made the first synthetic cell and tied with Human Genome Project to sequence the first human genome. He is not the only scientist trying to sequence large amounts of genomes to learn more about diseases. It has just been reported that a genetic study of 150,000 people resulted in the discovery of a mutation that reduces the risk of getting Type 2 diabetes. The cost to sequence one human genome will cost about $1,000 with the New X Ten System. Dr. Venter wants to sequence genomes from a large variety of people. He also wants to sequence people's microbiomes and measure chemicals in the bloodstream. Many scientists have praised Dr. Venter for his ambitious efforts in breakthrough science. He hopes to have enough funding so that Human Longevity will eventually be able to sequence 100,000 genomes a year along with their other studies.

A scientist at Dr. Venter's Synthetic Genomics prepares a sample of microorganisms. 

Dr. Venter has an impressive list of accomplishments and his goals are ambitious but possible. It his hard to argue with what he has done and what he is planning on doing. He does not want to make people live forever,  he just wants to give them a healthier life allowing them to live longer. He needs a lot of funding in order to sequence human genomes, but if his results enable diseases to be cured or prevented then all the money would have been well spent.

May Your Telomeres Live Long and Prosper

This past weekend, an article from ScienceDaily reports that researchers from the Intermountain Heart Institute at Intermountain Medical Center in Salt Lake City conducted a study that can predict survival rates among patients with heart disease based on the length of strands of DNA found on their telomeres. Basically, their findings state that the longer the patient's telomeres, the greater the chance of living a longer life.

John Carlquist, PhD, director of the Intermountain Heart Institute Genetics Lab, and his colleagues tested DNA samples from more than 3,500 heart attack and stroke patients. Dr. Carlquist stated that,

"Our research shows that if we statistically adjust for age, patients with longer telomeres live longer, suggesting that telomere length is more than just a measure of age, but may also indicate the probability for survival.” He goes on to say, "I believe telomere length could be used in the future as a way to measure the effectiveness of heart care treatment."

The researchers had two unique resources available to them. First, an archive of peripheral blood DNA samples collected from almost 30,000 heart patients, with as much as 20 years of follow-up clinical and survival data. Second, the opportunity to work with international experts that included Richard Cawthon, MD, PhD, a world-known expert on telomere measurement and function.

The institute’s studies were presented at the American College of Cardiology’s Annual Scientific Session in San Francisco on March 9. Further related research on the relationship between telomeres and longevity in mammals can also be found at ScienceDaily.

I have known that genetically the death of an organism will occur over a long period of time as the DNA replicates less and less of its self. I did not know that the telomeres were the culprit of this. I wonder though if there is a way to not only use the telomeres to measure age or the probability of survival but maintain their integrity to enhance longevity. After all, who doesn’t want to live forever? I sure do.