A research team led by Prof. KONG Qingpeng from Kunming Institute of Zoology of the Chinese Academy of Sciences reported that enhanced fatty acid oxidation is a key metabolic signature in centenarians. The study was published in Aging Cell.

As a natural model of healthy aging, centenarians not only enjoy exceptional longevity, but can also delay or even avoid the age-related diseases. Therefore, studying the features of centenarians may provide a new perspective and strategy for the early prevention and treatment of aging-related diseases and improving the health of the elderly.

Although it is well known that metabolic control plays a crucial role in regulating the health span and life span of various organisms, little is known for the systems metabolic profile of centenarians. Human metabolism is a complex network that contains thousands of reactions and metabolites, and systematic identification of metabolic changes in health and diseases remains challenging.

To address this challenge and better understand the metabolic mechanisms of healthy aging, Dr. LI Gonghua from Prof. KONG's team and the collaborators developed a method of genome-wide precision metabolic modeling (GPMM) to analyze the entire human metabolic network and discover key metabolic pathways and key metabolites corresponding to complex phenotypes (such as longevity, and disease). Compared with that of existing methods, the accuracy of GPMM is largely improved.

Using the GPMM method, the researchers systematically reconstructed and analyzed the metabolic network (including 3977 metabolic reactions) of centenarians and young controls, and found that enhanced fatty acid oxidation (FAO) was the most significant metabolic feature in centenarians. By measuring the serum metabolome data of the same longevity and control samples, they found that the lipids in centenarians were significantly lower than those of young controls, further supporting the conclusion that centenarians had enhanced fatty acid oxidation.

Given that FAO declines with normal aging and is impaired in many age-related diseases, this study suggests that the elevated FAO is a novel mechanism of healthy aging of humans.