MR linked me to some fascinating articles in my “Blue Zones” post, and I felt these needed to be written about. Most of my research has been very food oriented, so these papers allowed me to get into the subject of genetics and longevity. There is so much I still need to learn about! I usually have to dig for my next research venture, so having someone recommend some reading almost feels like cheating. Ha. Not that I am complaining, by all means people, sent links my way and support the *S.i.e* sponge! :-)  Well, this post is the result of my digging into two of these papers…..more to come later!

I only have the abstract for this paper, but I will present what I can. The authors note the search for longeivty genes in both animals and humans, and mention that studies currently (2006) indicate that ~20-30% of adult human lifespan variation is accounted for my genetic factors. When comparing identical and fraternal twins, there is a much stronger longevity correlation between identical vs fraternal twins. So, the probability that twin B will reach 60 is much higher if twin B has an identical twin A that reaches 60 rather than if twin B had a fraternal twin A that reaches 60. Females and males both have similar patterns, but females have a better survival rate overall. This study shows a strong genetic component of human longevity.

NOTE: Now, if one twin was a junk-food-aholic and the other was health conscientious, I wonder how the genetic component would factor in? How much can genes help you overcome a bad diet and lifestyle?  Obviously genes play a major role in our longevity, but at what point can they not compensate for lifestyle. I would like to know if the researchers of the study (or other studies out there) noted lifestyle differences and similarities between the twins on this study.

This article opens by mentioning the longevity of centenarians is partly due to their lack of genetic factors associated with premature death. Also, children of centenarians have notably reduced rates of age-related diseases. The main question driving this search for the genetic link to aging is people what to know how much they can influence their aging. If aging were 100% genetics, lifestyle would only matter in terms of risky behavior such as sky diving, and if genetics didn’t matter at all, we would have full control over our aging through lifestyle. Obviously, neither of these absolute solutions is the case, and the truth is somewhere in between.

Two genetic variations show increased/decreased rates of aging. People with progeria age at an extremely fast rate, and rarely live past 13 years of age. This condition is the result of a single gene mutation. Conversely, many centenarians lack the apolipoprotein E e4, which is associated with heart disease and Alzheimer disease, and instead have apolipoprotein E e2.

To further investigate the genetic link with longevity, the authors also studied the pedigrees of 444 centenarians and their 2092 siblings. The siblings showed significanlty higher survival probability rates when compared to the US Social Security’s life table for people born in 1900. Take a look at the table below to see the numbers for yourself.

Now, consider that not only do siblings have genetic similarity, but they often have similar environmental conditions However, the researchers point out that if the environmental factors were primarily associated with their longevity, the siblings’ longevity advantage should decline with age. So, among the subjects in this study, there was a high genetic correlation.
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NOTE-TANGENT: The author’s did not specifically clarify if the centenarians were all from the US or scattered across the world, so I pulled up their paper: Life-long sustained mortality advantage of siblings of centenarians, and found that indeed all 444 were from the USA. Another interesting statistic they reported is that the male siblings were 17 times as likely to reach 100, but the female siblings were only 8 times as likely to reach 100 when compared to the US 1900 Birth Cohort. They note these findings, while strong, were not inconsistent with several twin studies showing a genetic factor of 20-30%. However, they have this to say about the results:

They continue by saying if genes do significantly contribute to reaching an exceptionally old age, there are two classes likely responsible. The first type of genetic variable could be the lack of genetic polymorphism that predispose an individual to disease, for example the apolipoprotein E e4 (associated with cardiovascular disease and Alzheimers) and its replacement with apolipoprotein E e2. The second hypothesized genetic variable involves genes that slow aging on basic levels.
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The researches continue the genetic discussion by providing results from a New England Centenarian Study of 308 persons belonging to 137 families with exceptional longevity. Accourding the the results, Chromosome 4 appeared hold genes affecting longevity.

Of course, one of the hopes in discovering longevity genes is to facilitate the development of drugs to help people become more “centenarian like”. The authors continue by mentioning James Fries’ compression-of-morbidity hypothesis:

Basically, as we age, we will probably experience a higher rate of diseases with a longer suffering time. The researches also saw this hypothesis supported in general, *but* some centenarians did have long histories of age-related diseases. So, they further explored this to see if their appeared to be an adaptive factor helping these people survive in spite of living with debilitating, if not usually fatal, diseases.  Of the individuals studied:

So, more research desperately needs to be done to further analyze the genetic link to longevity. Complications are introduced through gene-gene interactions and gene-environment interactions that make cause and effect difficult to accurately determine at this stage in the research. However, there does appear to be significant gene contribution to extreme longevity, and through understanding this genetic factor, we can hopefully developing radical life extending therapies.

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I wonder how resilient these beneficial longevity genes are when compensating for poor lifestyle. Some people have made it to 100 while smoking and eating poorly, but others have lead an overall healthy lifestyle. Part of the problem in really determining cause and effect for this issue is the isolation and understanding of the variables at play. We are not sure of all the variables or the weights of of each one. Right now, we only have generalizations, and we are still far away from any sort of precise equation to accurately determine longevity. However, these generalizations are not to be taken lightly, we seem to have an idea of the breadth of the situation, we just don’t fully understand the depth at this moment.

Well, now back to other papers. What fun! :-)