UC Irvine Study Finds How Liver, Kidney Work Together to Support NAD⁺ and Healthy Aging

A groundbreaking study from UC Irvine has uncovered an unexpected mechanism by which the body maintains healthy energy metabolism. Central to this discovery is a surprising interplay between the liver and kidney to support a critical molecule called NAD⁺, which is essential for cellular energy, repair and longevity.

The study, “Nicotinic acid riboside maintains NAD⁺ homeostasis and ameliorates aging-associated NAD⁺ decline,” was recently published in Cell Metabolism.

"Reduced NAD⁺ has been linked to aging, diabetes, kidney dysfunction and neurodegenerative diseases. Accordingly, extensive efforts have focused on understanding how NAD⁺ is synthesized and metabolized,” says Cholsoon Jang, PhD, assistant professor of biological chemistry.  

"Traditionally, the liver was thought to be the main source of circulating nicotinamide, a key building block for NAD⁺ in other organs,” explains Qin Yang, MD, PhD, professor of medicine and physiology, chief of the Division of Endocrinology, and director of the UC Irvine Diabetes Center. “However, when we blocked the nicotinamide production from the liver, we serendipitously found that the liver produces another molecule, nicotinic acid riboside (NaR), which travels through the bloodstream to the kidneys. There, it is converted into NAD⁺ and helps restore balance across multiple organs."

Notably, the study shows that NaR levels naturally decline with age, and that supplementing with NaR can restore NAD⁺ levels, reduce inflammation and improve kidney health in older animals, according to Jang.

This major advance was made possible through a close collaboration between Yang's lab, known for its expertise in metabolic physiology and multi-omics research, and Jang’s lab, a leader in state-of-the-art metabolomics and metabolic flux analysis. By combining complementary strengths and cutting-edge technologies, the two teams were able to map out this new liver-kidney communication pathway and identify NaR as a promising target for promoting healthy aging. The study co-first authors are Won-suk Song, PhD; Xiyu Shen, MD, PhD; and Kang Du, MD, PhD, who are postdoctoral researchers from Jang's and Yang's laboratories.

"The breakthrough discovery not only advances our scientific understanding of NAD⁺ metabolism but also exemplifies the innovation that emerges when disciplinary boundaries are bridged,” says Michael J. Stamos, MD, dean of the UC Irvine School of Medicine. “It is precisely this kind of collaborative spirit that defines UCI and propels transformative research forward.”