Human longevity is affected by both genetics and lifestyle. You studied blood samples from a cohort of Dutch families who showed increased longevity, living very long time across several generations. What have you learned about your genetic analysis of aging in this Dutch families' longevity study? Yeah, I was fortunate while I was in Leiden, doing my internal medicine studies, to work with the Leiden longevity study and the Leiden 85-plus study. Leiden longevity studies is a very nice setup. We recruited nonagenarians and nonagenarian siblings. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. It means that somebody who has at the age of 90 a brother or sister also being 90. It shows the propensity that there's something special in these families, because you have two siblings in the family with long life. It also includes the offspring because 90-year-olds are quite fragile. I wouldn't say that they are frail, but then it's very important for us to see how their offspring are doing. The offspring, of course, have 50% of the genetic makeup of these nonagenarian siblings. The Principal Investigator is the study is Dr. Eline Slagboom from Leiden. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. We also included the partners of siblings as a control for the offspring of the nonagenarian siblings. We wanted to see what is the influence of living a long life in the family and having the controls next to that. So the controls are the husbands and the wives of this nonagenarian siblings. And what we were able to find is that yes, it seems that longevity runs in in families. The offspring of the nonagenarian siblings, for example, was compared to their husbands and wives living together with them. Nonagenarians had a much lower glucose level, and they had a better glucose regulatory system. We know that if the glucose level is a little bit lower, you have less chance of having diabetes, etc. But also other hormones like thyroid hormone were differentially regulated. And we were already at the age of offspring of nonagenarians, at about 60 years. We were able to see that they have less age-related diseases compared to their partners. It already then says, yes, it's proven that something is running in the families. These individuals were included in the genetic analysis because it might be the genes are very important for longevity. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. The longevity scientists think that about 20% of longevity is based on genetic makeup. We were able to find some genes like the ApoE gene was associated with longevity. But we really couldn't find a longevity gene. But we could find genes associated with diseases, which were absent in the individuals out of the long-living families. Very nice! We were also able to show that some genes were more highly expressed than others. So one of the gene families is in the mTOR pathway, for example. We saw that in the long-living families, these genes were differentially regulated. And mTOR is very important for making proteins and for lots of cellular signals. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD. The mTOR pathway is associated with the occurrence of disease and aging. So while having this very nice study design, we were able to dig a little deeper into the biology and show that offspring of nonagenarian siblings are quite different compared to their partners. And luckily, there have been study designs also doing that, for example, in Italy. It included centenarians and the offspring. And there are many other cohort studies now. They also show the same results to get a better understanding of the aging process itself. So, for example, it's the ApoE gene and certain alleles associated with the onset of dementia. So there is a huge network of genes. And that's not only one gene or the other gene, but it's a gene network, which is associated with longevity. So if you asked me this. Is the genetic analysis ready to be implemented into clinical care? Can we say, okay, you have a good genetic makeup or not. Also here, as I said for other biomarkers of biological age, that's not ready yet for introduction into clinical care. But what we know there are certain genes, which are more associated with the development of cancer or cardiovascular disease. But of course, these are genes being associated with the disease. Whereas we were looking for genes associated with longevity. Dr. Andrea B. Maier, MD. Dr. Anton Titov, MD.
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