Researchers here demonstrate an approach that can be used with large human epidemiological databases to demonstrate that, as expected, both greater amounts of visceral fat tissue and raised blood pressure cause reductions in life span. The underlying mechanisms have been explored at length by the research community. Visceral fat tissue produces chronic inflammation through a variety of mechanisms, including a raised burden of cellular senescence, while raised blood pressure produces damage to fragile tissues in the brain, kidney, and other organs, and accelerates the progression of atherosclerosis.
Researchers are exploring the cause and effect relationships between common health indicators and lifespan, by analyzing polygenic risk scores (PRS), a numerical score of a person's risk for disease based on multiple genetic variants. To find a clinically actionable indicator of genetic risk, researchers started by examining samples from BioBank Japan, which has a heavy East Asian representation. They used the genetic data of 180,000 people to perform genome-wide association studies for 45 common health indicators. By analyzing the PRS of each indicator, they identified the ones that most strongly affected lifespan.
"If you only look at raw clinical data associated to lifespan, you cannot show which attribute is cause and which is effect. For instance, when a patient is dying, their blood pressure is low, so you can't necessarily know if blood pressure is the cause of their death. By using PRS, we can get closer to identifying the cause, because PRS is less susceptible to the acquired confounding factors such as decline in general health."
For the individuals in BioBank Japan, researchers found that high blood pressure and obesity had the most significant associations to reduced lifespan. To improve the diversity of their study and ensure that these associations held across populations, the researchers collaborated with the UK Biobank and FinnGen, and performed a trans-ethnic association study of PRS and lifespan. This increased the sample size to 700,000 and, with the help of additional analyses, reinforced the conclusion that blood pressure and obesity are causally related to reduced lifespan.