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Published on: September 17, 2020
Specific differences and novel key regulatory genes of sex in influencing exceptional longevity phenotypes
Xiaolin Ni1, Huabin Su2, Gong-Hua Li3
1Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Peking Union Medical College, Beijing, 100005, PR China; The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology of National Health Commission, 100730, PR China.
Background And Aims:
Although the life expectancy of women systematically and robustly exceeds that of men, specific differences and molecular mechanisms of sex in influencing longevity phenotypes remain largely unknown. Therefore, we performed transcriptome sequencing of peripheral blood samples to explore regulatory mechanisms of healthy longevity by incorporating sex data.
Methods:
We selected 34 exceptional longevity (age: 98.26 ± 2.45 years) and 16 controls (age: 52.81 ± 9.78) without advanced outcomes from 1363 longevity and 692 controls recruited from Nanning of Guangxi for RNA sequencing 1. The transcriptome sequencing 1 data of 50 samples were compared by longevity and sex to screen differentially expressed genes (DEGs). Then, 121 aging samples (40-110 years old) without advanced outcomes from 355 longevity and 294 controls recruited from Dongxing of Guangxi were selected for RNA sequencing 2. The genes associated with aging from the transcriptome sequencing 2 of 121 aging samples were filtered out. Finally, the gender-related longevity candidate genes and their possible metabolic pathways were verified by cell model of aging and a real-time polymerase chain reaction (RT-PCR).
Results:
Metabolism differs between male and female and plays a key role in longevity. Moreover, the principal findings of this study revealed a novel key gene, UGT2B11, that plays an important role in regulating lipid metabolism through the peroxisome proliferator activated receptor gamma (PPARG) signalling pathway and ultimately improving lifespan, particularly in females.
Conclusion:
The findings suggest specific differences in metabolism affecting exceptional longevity phenotypes between the sexes and offer novel therapeutic targets to extend lifespan by regulating lipid homeostasis.
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