Live to be 100? DITM Tells You How

A study from the University of Chicago has been getting a lot of press attention lately.  They found that your chances of living to 100 may depend on how young your mother was when she gave birth to you with chances doubled if mom was under 25.  The reports do not give the explanation why. 

DITM has the Answer: Buried in an IVF session at the Annual ASRM (American Society for Reproductive Medicine)  meeting (and missed by most people at the meeting) was a unified theory of reproductive aging and human longevity.  It was the most amazing thing I saw at the meeting.

Dr. David Keefe of U Florida (a fertility doctor and one of my former partners at Yale) presented data on the telomere and its role in reproductive aging.  The telomere is a piece of repetitive DNA (the same exact little sequence over and over again) that does not code for any proteins.  It is a protective cap on the end of the chromosome.  Human DNA replication is tricky since the enzymes that copy DNA cannot copy the very end of the DNA strand.  The body protects itself by having this telomere, or protective non-coding DNA at the end.  Unfortunately as cells divide this cap starts to get lost.

It has been shown that the telomeres shorten with normal aging by two mechanisms: 1) repetitive cell and DNA division with each separation of a cell into daughter cells and 2) reactive oxygen radical induced damage (the stuff anti-oxidants are supposed to protect against) followed by excision repair by the body.  Telomeres are very susceptible to this particular kind of damage.  

Interestingly, developing embryos lack telomerase- one of the enzymes necessary for repair of damage to telomeres.  Telomeres are also the area when chromosomes pair together - a vital step just before the cell divides.  Therefore in a developing embryo with damage to the telomere the chromosomes do not pair normally and the result is uneven separation of chromosomes.  This is the #1 cause of miscarriage as a woman ages and the #1 cause of birth defects that increase as a woman ages.  It is also the #1 reason fertility is reduced in older moms.

Here is where it gets even more amazing.  The first eggs formed in fetal life in a woman (as a fetus a woman forms all of the eggs she will ever have as an adult) have the longest telomeres and ovulate earliest in her reproductive years.  The ones that are formed last have the most telomere damage because they had to divide the most times, have the shortest telomeres, and ovulate last in a woman’s late 30’s and 40’s.  Eggs with shorter telomeres have been shown in IVF to be less likely to lead to a pregnancy, and more likely to lead to abnormal embryo development.  So the short telomere theory completely explains reproductive aging and miscarriages and the increase in genetic abnormalities seen in offspring of older women.

Connection to Aging and Longevity:  As a human ages there is further telomere damage that cannot be repaired.  As this accumulates cells enter a form of cell death called apoptosis.  This entire process will be accelerated in the offspring of older mothers (because all of the cells formed from an egg with shorter telomeres in the first place) leading to earlier death– exactly what this new research from U Chicago shows.

What Can Be Done:  There are enzymes that COULD repair the broken telomere ends.  The main one telomerase exists in some cells but is largely turned off.  It will take genetic engineering to make it active in all aging cells.  When that occurs older cells could be repaired to the state of younger ones.  In other words a genetically engineered fountain of youth. 

Scientists are actively pursuing this: Geron Corporation back as early as 1990 developed drugs that extended telomeres, and proved that they prevented cellular aging and death.  In fact, When normal cells are altered in the laboratory to make the enzyme telomerase that repairs telomeres they continue to live far longer than they ever should.  This remarkable demonstration (reported by Bodnar et. al. in the January 16 1998 issue of Science) provides the most compelling evidence yet that telomerase and maintenance of telomere length are the key to cell immortality.

The Problem Stopping This Treatment: The same enzymes that repair the cell when turned on excessively lead to cancer formation.  To make this an effective treatment will require scientists to be able to turn the enzymes on and off or on in a regulated manner.  This is all possible.

Well if the treatment is not here yet you can always trigger long term human hibernation until it is available.

Further Reading:  Here is a link to telomere and life extension .  Here is a highly technical review of telomeres and the problems with then leading to aging.  Here is a fairly high tech paper on telomeres and aging vs cancer.  If you really want the in depth science and have a PhD this is for you.

Update: The reproductive study author Dr. Keefe took the time to answer many of my questions about how all this works (and goes wrong as we age).  His answers can be found here.