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 paper entitled “System-level metabolic modeling facilitates unveiling metabolic signature in exceptional longevity” 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 and others 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, disease, etc.). Compared with 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, the results showed that the lipids in centenarians were significantly lower than that 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. 

This study, entitled “System-level metabolic modeling facilitates unveiling metabolic signature in exceptional longevity”, was published in Aging Cell. Weblink: https://onlinelibrary.wiley.com/doi/10.1111/acel.13595. Prof. KONG Qingpeng, Prof. HUANG Jingfei and Prof. XIAO Wenzhong are the co-corresponding authors, Dr.LI Gonghua is the first author. The study is led by the Kunming Institute of Zoology, Chinese Academy of Sciences, with help from Harvard Medical School in algorithm design, and is financially funded by National Key R&D Program of China, the National Natural Science Foundation of China, the Chinese Academy of Sciences, the Science and Technology Department of Yunnan Province, and Kunming Science and Technology Bureau.

GPMM metabolic modeling workflow and the main findings

(Image by Li et al., DOI:  https://doi.org/10.1111/acel.13595)

Weblink: https://onlinelibrary.wiley.com/doi/10.1111/acel.13595

(By LI Gonghua, Editor: YANG Yingrun)

Contact:

KONG Qingpeng

kongqp@mail.kiz.ac.cn