August 11, 2007
Life Expectancy And Telomere Length More Inherited From Fathers?

Research on the Old Order Amish points to connections between fathers, children, telomere length, and life expectancy.

Telomeres, pronounced TEE-low-meres, are DNA caps. They protect genes at the tips of chromosomes — all 23 pairs that reside in the nucleus of each of our trillions of cells. They are kind of like the tips that keep your shoelaces from unraveling.

A handful of studies indicate that telomeres are shorter in the immune cells of older people in comparison with the young. Now, a research team led by UCSF’s Wen-Chi Hsueh, MPH, PhD, suggests that telomere length might be associated with life span itself. Hsueh and colleagues published their very preliminary findings in the July 17 issue of the Proceedings of the National Academy of Sciences (PNAS).

The PNAS study co-authors believe they are the first to report an association between telomere length and life span. But the finding needs to be confirmed, Hsueh says, as more data on life span become available. Only 35 study participants have died so far.

Telomeres are caps on the ends of chromosomes. Current thinking is that every time a cell divides its telomere caps get shorter. Once the telomeres get short enough cells have a hard time dividing and perhaps become senescent. The telomere cap length shortening might be a mechanism for reducing the incidence of cancer. So if we could find a way to lengthen telomere caps of cells in our bodies any resulting rejuvenation might come at the expense of greater incidence of cancers. So you die from your cells not dividing enough or you die from your cells dividing too much.

At least in this Old Order Amish population the telomere lengths in fathers appear to correlate with the telomere lengths in their offspring.

The researchers discovered that average telomere length in fathers — but not mothers — was related to telomere length in children. Moreover, the researchers found an association between daughters’ telomere length and how long their fathers lived. This suggests that life span and telomere length may share some genetic determinants.

“It’s very rare to observe such a paternal inheritance phenomenon for complex traits, so I was very surprised,” Hsueh says.

The likely explanation is a biological phenomenon known as imprinting, Hsueh says. In imprinting, the activity of certain genes depends on whether they were passed down through one’s mother or one’s father. The maternal gene copies are not active. The exact mechanism by which imprinting might affect the inheritance of telomere length remains mysterious, Hsueh says.

I'm even more interested in the "Why?" than the "How?" about this effect. What advantage is there (if any) to having the father's telomere lengths exert a stronger influence on offspring than the mother's telomere lengths? Does some adaptive advantage come from this? Or is it a side effect of something else that was selected for?

The study was done on Old Order Amish in Pennsylvania because they are genetically fairly homogeneous and live very similar lifestyles to each other.

The Amish fit the bill. They have a small number of ancestors — about 200 Amish families came to the United States from Europe about 14 generations ago, during the early to mid-1700s. Now, there are about 30,000 Old Order Amish living in Lancaster County. They do not marry outsiders. As a result, they have little variability in their genes — a small gene pool. That reduces the complexity of finding genetic variants that may be associated with particular traits or diseases within the population.

There also is little variation in lifestyle and environment to complicate the study of genetic influences on aging, Hsueh notes. Amish women do not smoke or drink, and those behaviors also are very rare among Amish men. The Amish eat together in large groups and have similar schedules.

Highly homogeneous populations are very handy for teasing out various potential causes of differences in development and diseases.

Even though telomere lengthening would probably increase risk of cancer that will not always be the case. Picture, say, 10 or 20 years from now. Suppose an effective and controllable technique for telomere lengthening is found (probably a gene therapy that includes telomerase genes). How can telomere lengthening get used to increase life expectancy without increased death from cancer?

First off, we might have 100% effective cures for cancer 20 years from now. Certainly we will sooner or later. Whenever we develop the ability to cure cancer we'll be able to make use of many treatments that have the side effect of increasing cancer risk.

Second, we will gain the ability to selectively apply telomere lengthening only to cells which have no mutations that increase risk of cancer. Hiow? Take a bunch stem cells out of a body. Put each individually in a small tube with nutrients. Send in gene therapy to fix each cell's telomeres. Let each cell divide. Take just one cell out of each tube. Test for DNA mutations that increase cancer risk. Go back to the small tubes that contain cells which have no detectable cancer risk and let them replicate in much larger numbers. Then reinject those stem cells back into the body.

Third, repair the genes that have accumulated mutations that contribute to cancer. The third approach is similar to the second approach except more extensive gene therapy will get placed into each cell in order to repair the genes that have dangerous mutations. Basically, repair all the mutations that could contribute to cancer. Then telomere lengthening could be done safely without boosting cancer risk.

We need greater efforts to start testing out stem cell rejuvenation therapies such as telomere lengthening. This work could get done in rats, mice, and other non-human species and would provide useful indications on what kinds of stem cell rejuvenation therapies will work best.

If we could find a way to rejuvenate stem cells without boosting cancer risk then we could probably prevent and even reverse many degenerative old age diseases. See, for example, my previous post Bone Marrow Stem Cell Aging Key In Atherosclerosis.

Also see my previous posts "Telomere Length Indicates Mortality Risk" and "Chronic Stress Accelerates Aging As Measured By Telomere Length" and New Telomere Lengthening Technique Developed and Telomeres Wear Down Quicker In Men Than Women and Aged Blood Stem Cells Indicator For Cardiovascular Disease Risk.

Share |      Randall Parker, 2007 August 11 02:09 PM  Aging Mechanisms

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