Targets for drugs that could improve the length and quality of human life are difficult to find. Genetics research could be helpful to find connections between specific proteins encoded by the genes and the health status and lifespan of humans. However, this approach has had limited success so far.
Paul R. H. J. Timmers, University of Edinburgh, UK, and colleagues have combined the results of six large genetic studies that looked at associations between genes and human aging traits such as the length of life, the length of healthy life (called “healthspan”), the lifespan of father and mother of the subject, frailty, and self-rated health. The team found 27 genomic regions associated with length of life and indices of mental and physical wellbeing.
The researchers also looked at the genes encoding 857 different proteins, using so-called Mendelian randomization (MR) to find possible causal links between the levels of the proteins and health and aging. Two proteins, in particular, had significant negative effects across various aging measures in subjects with genes that cause higher levels of these proteins.
One protein, apolipoprotein(a) (LPA), binds and transports lipids. High levels of LPA can increase the risk of atherosclerosis (clogged arteries). The second protein, vascular cell adhesion molecule 1 (VCAM1), is primarily found on the surfaces of endothelial cells—i.e., cells in the lining of blood vessels. The protein influences the adhesion of cells to the lining of blood vessels and the migration of white blood cells across the endothelial walls. According to the researchers, LPA and VCAM1 could be possible drug targets for improving the quality and length of life.
- Mendelian randomization of genetically independent aging phenotypes identifies LPA and VCAM1 as biological targets for human aging,
Paul R. H. J. Timmers, Evgeny S. Tiys, Saori Sakaue, Masato Akiyama, Tuomo T. J. Kiiskinen, Wei Zhou, Shih-Jen Hwang, Chen Yao, Yoichiro Kamatani, Wei Zhou, Joris Deelen, Daniel Levy, Andrea Ganna, Yoichiro Kamatani, Yukinori Okada, Peter K. Joshi, James F. Wilson, Yakov A. Tsepilov,
Nat. Aging 2022.