What can the world’s oldest people tell us about ageing?

Image by Utkarshsingh via Wikimedia Commons
Indian supercentenarian Kallu Yadav. Image by Utkarshsingh via Wikimedia Commons

Scientists recently sequenced the genomes of 17 of the oldest people alive in the USA to see if their genes could tell us the key to slowing ageing. The people studied were all supercentenarians – over 110. When the paper was published in November 2014, there were 74 supercentenarians known in the world. Sixteen of the people in the study were women and only one was a man. Fourteen of the American supercentenarians were white, one was African American, and two were hispanic. This is similar to previous studies showing that people over 100 are most likely to be white, female and have a college education. 

Interestingly, centegenarians’ sisters are eight times more likely to live to 100 than the average person and their brothers are 17 times more likely to become centenarians themselves. Only 5-10% of this sibling advantage can be explained by race and education. So it would make sense if these long-lived siblings had genes that were somehow different to the rest of us and allowed them to live for such a long time and to be healthy almost up to the end of their life.

The extended healthspan (years of living without disease) enjoyed by supercentenarians isn’t because of better lifestyle choices. They have the same rates of smoking and drinking, the same diets and the same exercise habits as shorter lived populations. Yet they have much lower rates of age-related diseases than average. In the US 45% of 85 year olds have had cancer and 35% have been diagnosed with cardiovascular disease. In contrast, in this study of 17 supercentenarians, none had heart disease, stroke or diabetes, only one had cancer, and one had Alzheimer’s disease. This is one of the major ironies of ageing: once you make it to 100, you are much less likely to develop age-related diseases like cancer and heart disease. Also mortality rates flatten out after 100, so as you get older you are no more likely to die. This happens all up and down the evolutionary tree from invertebrates like worms, flies and shrimps to rodents and right up to humans.

Previous studies have shown that people who live longer are more likely to have a variation in one of two genes that control how our cells sense nutrient levels: Insulin-like Growth Factor 1 Receptor gene (IGF1R) and the FOXO3 transcription factor. Inhibiting these genes in worms and flies also allows them to live longer.

However this study did not find a genetic variation that gives the supercentenarians their power to slow the effects of ageing. This might be because the study only looked at 17 people. If they had looked at 100 people, it may have been easier to sort out differences between supercentenarians and regular people. But more likely, this result tells us that ageing is probably not controlled by one gene, or even a few genes.

Another problem with this study is that it only looked a the part of the genome that encodes for genes (the DNA code that cells use to make proteins). This is only 1-2% of the genome. So there could easily have been changes in the other 98-99% that were missed. We now know that the other 98% of DNA controls which genes are turned on and off in different cells and in response to changes in our environment such as any change in diet or when we get sick. So the supercentenarians might have different levels of genes (gene expression) in various parts of their bodies without having any changes in the DNA sequences that codes for genes.

Or the supercentenarians might have different epigenetic marks on their DNA. Epigenetic changes to DNA can be inherited and can be caused by many different things including diet.

Or the supercentenarians might have something different in their blood. Recently a number of studies have shown that young mice have more GDF11 in their blood than old mice, and if old mice are given GDF11 it can reverse heart and brain disease.

So perhaps this study was too simple to find the answer to the complex problem of ageing. But this data is available for anyone to play with. It is free and open access and the authors encourage people to have a look at it to see if they can uncover anything that has been missed. Now that is collaborative science.

The Scientific Papers (free and open access):

Gierman et al. Whole-Genome Sequencing of the World’s Oldest People. PLoS One. 2014

Perls et al. Life-long sustained mortality advantage of siblings of centenarians. PNAS. 2002

Gavrilov and Gavrilova. Mortality of Centenarians: A Study Based on the Social Security
Administration Death Master File. Presented at Princeton. 2005.

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