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Lifebrain Monthly E-newsletter March 2020

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The genetics of human ageing

What is ageing?
Ageing is characterized by reduced number of cells in many organs and decline in several important functions. It may lead to poorer performance in everyday physical and cognitive tasks. Ageing also increases the risk of common diseases like Alzheimer’s disease, stroke, cancer, chronic kidney disease, cardiovascular diseases, osteoarthritis and type 2 diabetes mellitus (T2DM). Although the decline in functioning is characteristic of ageing, the rates of decline vary greatly between people. 

Photo by Vlad Sargu on Unsplash

Many age-related changes and disorders seem to have substantial heritable components. Heritability describes the proportion of variance in a trait (the differences between people) that can be due to genetic differences among individuals in a given population. Describing the genetic variation that influences human ageing may help identify suitable targets for effective anti-ageing interventions. Large groups of people with and without the trait of interest need to be analysed to monitor the genetic contribution. Here we describe the results of some large genetic studies investigating different aspects of ageing. 

Results from genetic studies on aging
In one study approximately 20000 participants in the age of 51–61 years were followed up for 18 years. The researchers behind the study examined whether the participants’ health at a given time was associated with their parents’ age at death. They found that cancer incidence is lower in participants with long-lived parents and that for every decade the participants’ mothers had lived beyond the age of 65, the participants’ own mortality declined by 19% (14% per decade for fathers) (Dutta et al., 2013). Another study (Deelen et al., 2019) of more than 10000 participants found that participants who lived longer than “normal,” had a lower frequency of a well-known genetic marker (the so-called ApoE ε4 variant) than participants having a shorter than “normal” lifespan. Interestingly, this genetic marker is also an important contributor to Alzheimer’s disease (Jansen et al., 2019) and cardiovascular diseases (Nikpay et al., 2015). 

Cognition and ageing

Normal ageing is often associated with impaired cognition, even in the absence of dementia. A recent genetic study investigating the decline in cognitive ability in more than 1000 people observed that the APOE region was the strongest predictor of cognitive decline from age 70 to 79 (Ritchie et al., 2019). 
The genetic contribution to the most common diseases of ageing, including Alzheimer’s disease, stroke, cardiovascular diseases, T2DM and common cancers, is extensively studied, resulting in exciting insights into their molecular mechanisms. However, for many of these diseases, the exact mechanisms remain unknown, and much more work is needed to establish the underlying biological mechanisms. Overall, human genetic studies will probably continue to provide growing insight into how we age and play a role for promoting a more “healthy ageing”. 

The referred studies

Deelen, J., Evans, D. S., Arking, D. E., Tesi, N., Nygaard, M., Liu, X., . . . Murabito, J. M. (2019). A meta-analysis of genome-wide association studies identifies multiple longevity genes. Nature Communications, 10(1), 3669. doi:10.1038/s41467-019-11558-2

Dutta, A., Henley, W., Robine, J.-M., Langa, K. M., Wallace, R. B., & Melzer, D. (2013). Longer Lived Parents: Protective Associations With Cancer Incidence and Overall Mortality. The Journals of Gerontology: Series A, 68(11), 1409-1418. doi:10.1093/gerona/glt061

Jansen, I. E., Savage, J. E., Watanabe, K., Bryois, J., Williams, D. M., Steinberg, S., . . . Posthuma, D. (2019). Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nature Genetics, 51(3), 404-413. doi:10.1038/s41588-018-0311-9

Nikpay, M., Goel, A., Won, H.-H., Hall, L. M., Willenborg, C., Kanoni, S., . . . the, C. D. C. (2015). A comprehensive 1000 Genomes–based genome-wide association meta-analysis of coronary artery disease. Nature Genetics, 47(10), 1121-1130. doi:10.1038/ng.3396

Ritchie, S. J., Hill, W. D., Marioni, R. E., Davies, G., Hagenaars, S. P., Harris, S. E., . . . Deary, I. J. (2019). Polygenic predictors of age-related decline in cognitive ability. Molecular Psychiatry. doi:10.1038/s41380-019-0372-x

Source of newsletter

This newsletter was edited by Céline Sonja Reinbold, Postdoctoral research fellow at Centre for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo.


Your comments are always valuable to us, so do not hesitate to contact us.

Center for Lifespan Changes in Brain and Cognition at the University of Oslo
Kristine B. Walhovd project coordinator
Mari R. Arnesen administrative coordinator
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This project has received funding from the European Union ’s Horizon 2020 research and innovation programme under grant agreement No 732592.
Copyright © 2020 Lifebrain Horizon2020 project, All rights reserved.

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