Health,Stem Cells, and Technology

Sunday, December 30, 2012

Short Telomere Length Linked To Risk Of Dying

The protective caps on the ends of chromosomes called telomeres may portend a higher risk of death. A new, large study,The Genetic Epidemiology Research on Adult Health and Aging (GERA), reports data on telomere lengths and genotypes of over 675,000 SNPs for each of 100,000 subjects.
Telomeres prevent a chromosome’s DNA from being eaten away or damaged. Previous studies have shown that telomeres shorten with age and have linked short telomeres with several diseases. However no one has previously reported whether  truncated telomeres cause health problems or are a side effect of aging and poor health.
To better understand, researchers at Kaiser Permanente and the University of California, San Francisco measured telomere length in 110,266 people in northern California. The participants were part of an ongoing project that explores links between genetics and health. This study is the largest ever to examine the role of telomeres in health.
The 10 percent of people with the shortest telomeres had a more than 20 percent higher risk of dying than people with longer telomeres, reported November 8 at the annual meeting of the American Society of Human Genetics. The study suggests that once your telomeres become critically short, your risk of dying increases. The increased death risk is about the same as for people who drink 20 to 30 alcoholic beverages per week or smoke for 20 to 30 years.  The increased risk is small, but significant.
Telomeres do shorten with age, the study confirms, but men older than 75 and women over age 80 tended to have longer telomeres than their slightly younger counterparts. The result seems counterintuitive, and does not mean that telomeres start to grow in length once people reach a certain age. Rather, the finding probably means that people with shorter telomeres died before they reached those ripe old ages and the survivors are those that carry longer telomeres.
African-Americans tended to have longer telomeres than European-Americans, Latinos or Asians, the researchers found. The reason for that difference is not clear. As expected, people who smoked or drank heavily were more likely to have shorter telomeres, and higher levels of education were associated with longer telomeres. Other studies have linked exercise with longer telomeres, but Dr. Schaefer, the PI, and her colleagues found no such association.
One of the study’s findings is rather puzzling: Higher body mass index, or BMI, was associated with longer telomeres.  Although a high BMI is not healthy, more work will be needed to understand the relationship between body size and telomere length.
While the study is important, over reaching conclusions should not be drawn given the study used the biomarker of telomeres taken from saliva samples. Telomeres from cells in other parts of the body, something hard to sample in human studies such as this one, will be one, amongst other additional studies that are required to better understand telomeres in aging and health.

Friday, December 7, 2012

Transposable RNA Elements Control Gene Expression And May Lead To Speciation

Numerous studies over the past decade have elucidated a large set of long intergenic noncoding RNAs (lincRNAs) in the human genome. Research since has shown that lincRNAs constitute an important layer of genome regulation across a wide spectrum of species. However, the factors governing their evolution and origins remain relatively unexplored. One possible factor driving lincRNA evolution and biological function is
transposable element (TE) insertions. In a study at Harvard and MIT, led by Drs. David Kelley, Ph.D. and John Rinn, Ph.D., they comprehensively characterize the TE content of lincRNAs relative to genomic averages and protein coding transcripts.

Dr Kelley and Dr Rinn realized that the movement within the genome of transposable elements can be considered a mutation, and wondered if this mutation has evolutionary consequences. They think it does because when they looked at the relation between such elements and lincRNA genes, they found a number of patterns. First, lincRNAs are much more likely to contain transposable elements than protein-coding genes. More than 83% do so, in contrast to only 6% of protein-coding genes. Second, those transposable elements are particularly likely to be endogenous retroviruses, rather than any of the other sorts of transposons. Third, the TEs are usually found in the bit of the gene where the process of copying RNA from the DNA template begins, suggesting the TEs are involved in switching genes on or off. And fourth, lincRNAs containing one particular type of endogenous retrovirus are especially active in pluripotent stem cells, the embryonic cells that are the precursors of all other cell types. That datum suggests these lincRNAs have a role in the early development of the embryo.

Previous work suggests lincRNAs are also involved in creating the differences between various sorts of tissue, since many lincRNA genes are active in only one or a few cell types. Given that their principal job is regulating the activities of other genes, this makes sense. Even more pointing, studies of lincRNA genes from species as diverse as people, fruit flies and nematode worms, have found they differ far more from one species to another than do protein-coding genes. The lincRNA are, in other words, more species specific. And that suggests they may be more important than protein-coding genes in determining the differences between those species.

What seems to be happening is that endogenous retroviruses are jumping around in an arbitrary way within the genome. Mostly, that will, in evolutionary terms, be either harmless or bad. Occasionally, though, a retrovirus lands in a place where it can change the regulation of a lincRNA gene in a way beneficial to the organism. Such variations are then spread by natural selection in the way that any beneficial mutation would be. But because the variation affects developmental pathways and tissue types, and thus a creature’s form, rather than just a simple biochemical pathway, that could encourage the formation of a new species.

Thursday, December 6, 2012

Epigenome: The DNA Methylome Helps Predict Aging

The epigenome, which is the set of modifications to DNA other than changes in the sequence of DNA, is associated with aging. The ability to measure human aging from molecular profiles has practical implications in many fields, including disease prevention and treatment, forensics, and extension of life. Although chronological age has been linked to changes in DNA methylation, the methylome has not yet been used to measure and compare human aging rates. Researchers at UCSD (Hannum et al, 2012), have built a quantitative model of aging using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101. This model measures the rate at which an individual’s methylome ages, which we show is impacted by gender and genetic variants. They also show that differences in aging rates help explain epigenetic drift and are reflected in the transcriptome. They also show how their aging model is upheld in other human tissues and reveals an advanced aging rate in tumor tissue. The model highlights specific components of the aging process and provides a quantitative readout for studying the role of methylation in age related disease.