Telomere length is a driving hallmark for aging-related biochemical hallmarks: evidence from the shared genetic effect and causal inference
Author: Ben Niu1,2, Jia-Xin Wu1,2, Xiao-Li Huang3, Shu-Feng Lei1,2, Fei-Yan Deng1,2
Affiliation:
1 Collaborative Innovation Center for Bone and Immunology between Sihong Hospital and Soochow University; Center for Genetic Epidemiology and Genomics, School of Public Health, Suzhou Medical College of Soochow University, Jiangsu, P. R. China.
2 Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Soochow University, Suzhou, Jiangsu, P.R. China.
3 Collaborative Innovation Center for Bone and Immunology between Sihong Hospital and Soochow University; a Department of Orthopedics, Sihong Hospital, Jiangsu, P. R. China.
Conference/Journal: J Gerontol A Biol Sci Med Sci
Date published: 2023 Dec 22
Other:
Pages: glad275 , Special Notes: doi: 10.1093/gerona/glad275. , Word Count: 184
Telomere shortening is an important sign and driving factor of aging, but its association mechanisms and causal effects with other aging-related biochemical hallmarks are largely unknown. This study first performed comprehensive genetic analyses (e.g., shared genetic analysis, pleiotropic analysis, gene enrichment analysis) to detect the underlying molecular mechanisms for the associations between TL and aging-related biochemical hallmarks. Then, further bidirectional MR analyses investigated the causal effects between TL and other biochemical hallmarks. The genetic correlations were negative between TL and GDF15 (P = 0.024), CRP (P = 0.007), HbA1c (P = 0.007) and RBC (P = 0.022), but positive between TL and IGF-1 (P = 0.002) and WBC (P = 0.007). The increased TL has causal effects on the low levels of GDF15 (P = 3.73E-06), SHBG (P = 6.30E-06), testosterone (P = 5.56E-07), FI (P = 2.67E-05), and RBC (P = 1.54E-05), but the higher levels of IGF-1 (P = 3.24E-07). In conclusion, the observed phenotypic correlations between TL and aging-related biochemical hallmarks may arise from a combination of shared genetic components and causal effects. TL is regarded as a driving hallmark for aging-related biochemical hallmarks.
Keywords: aging; causal inference; genetic effect; hallmark; telomere length.
PMID: 38134301 DOI: 10.1093/gerona/glad275
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