Kaori Hayashi: Kidney Disease Accelerates Aging

2023/12/14

Chronic kidney disease (CKD) is steadily increasing against the backdrop of an aging society, and it is now said that one in eight Japanese people has CKD. It is known that the workload of the kidneys (glomerular filtration rate) decreases with age. However, the kidney is known as a "silent organ," showing few symptoms until renal failure progresses, and many people may think that as long as they don't end up on dialysis, it's fine even if their kidney function declines.

However, in recent years, it has become clear that CKD is a major risk for life-threatening cardiovascular complications. Furthermore, it has recently been discovered that the presence of CKD significantly accelerates the aging of other organs (Nat Med 2023). In other words, to prevent systemic aging as much as possible, one must pay attention to kidney function.

I became a nephrologist because I was drawn to the depth of the kidney, which does more than just produce urine. While being involved in the clinical care of kidney disease, I am conducting research with other doctors in the department to understand new pathologies and find therapeutic targets for kidney disease. Recently, I have been conducting research focusing on the epigenome and DNA damage in the kidney. Epigenetic regulation is a mechanism of gene expression control that does not depend on the DNA base sequence, and it has recently been suggested to have a deep connection with cancer and aging. As the name suggests, there are several types of epigenomes, such as DNA methylation and histone modification on the genome. On the other hand, DNA damage is also closely related to cancer and aging, and DNA damage repair is an essential mechanism for sustaining life.

When damaged DNA is repaired, epigenetic information should ideally be restored as well; however, failure to return to its original state causes various adverse effects and is thought to be involved in the pathology. In our research, it is becoming clear that DNA damage in the kidney and the associated epigenetic changes are involved in the pathology of CKD; furthermore, it is suggested that DNA damage in the kidney is also deeply related to the progression of systemic aging.

It would be very interesting if DNA damage in the kidney were one of the origins of "aging," which is the root of various diseases. Aiming to elucidate the hidden power of the kidney, I want to conduct research that can be translated back to clinical practice together with the doctors in the department, while learning about rapidly advancing new concepts and analytical methods.