Metabolic profiling of the Chinese population with extreme longevity identifies Lysophospholipid species as potential biomarkers for the human lifespan

Background

Metabolic regulation plays a crucial role in extending the healthspan and lifespan across multiple organisms, including humans. Although numerous studies have identified the characteristics of the metabolome and potential biomarkers in long-lived populations worldwide, the metabolome landscape of Chinese centenarians remains largely unknown. This study characterised the plasma metabolic profiles of Chinese centenarians and nonagenarians and identified potential biomarkers of longevity.

Methods

A global untargeted metabolomics approach was used to analyze plasma samples from 65 centenarians (average age 101.72 ± 1.46 years), 53 nonagenarians (average age 98.92 ± 0.27 years), 47 older individuals (average age 64.66 ± 3.31 years), and 35 middle-aged participants (average age 33.91 ± 3.53 years) recruited from the Lishui region, an area of China well known for the longevity of its population.

Results

The plasma metabolic profiles of centenarians and nonagenarians differed significantly from those of the two younger populations. Specifically, 211 and 114 differentially abundant metabolites (DAMs) were identified in the centenarian and nonagenarian groups, respectively. The majority of these DAMs were glycerophosphoethanolamines, glycerophosphocholines, fatty esters, fatty alcohols, fatty acyls, and fatty acids and conjugates. For example, the circulating levels of LysoPA (20:2), LysoPA (20:3), LysoPC (16:0), LysoPC (18:2), and LysoPE (20:4) were significantly lower in centenarians than in the older and middle-aged groups. A similar pattern was also observed in the nonagenarian population. Notably, the plasma levels of five DAMs – LysoPA (20:3), LysoPC (18:2), LysoPE (20:4), PG (18:0/18:1), and PG (18:1/18:2) – were significantly and continuously reduced with the ageing process. Pearson correlation analysis revealed that the reduced abundance of LysoPA (20:3), LysoPC (18:2), LysoPE (20:4), LysoPE (24:0), PG (18:0/18:1), and PG (18:1/18:2) was significantly and negatively associated with lifespan, from middle-age to centenarian. ROC analysis indicated that LysoPA (20:3), LysoPC (18:2), LysoPE (20:4), LysoPE (24:0), PG (18:0/18:1), and PG (18:1/18:2), as well as the combination of these six DAMs (AUC = 0.9074), had high predictive power for the human longevity phenotype.

Conclusion

This study elucidated the plasma metabolic landscape of centenarians and nonagenarians in China and identified several potential biomarkers for predicting human lifespan. Our findings will aid in understanding the metabolic regulation of longevity and may promote the clinical practice of gerontology in the future.