Evidence for the causal relationship between age at first sexual intercourse and multidimensional aging phenotypes from a full life cycle perspective: A mendelian randomization study

Abstract

Background: The full life cycle perspective emphasizes the profound impact of early-life events on later health. Age at first sexual intercourse (AFS) marks the onset of an individual’s sexual development and behavior, which may influence the aging trajectory.
Objective: This study aims to investigate the causal effects of AFS on multidimensional aging phenotypes and identify potential mediating mechanisms from a full life cycle perspective.
Study design: Mendelian Randomization (MR) analysis.
Methods: This study employed two-sample MR analysis, using genetic instruments for AFS to estimate its causal effects on various aging phenotypes, including aging-genetically independent phenotypes (aging-GIP), longevity, frailty index, parental lifespan, healthspan, and self-rated health. Subsequently, a two-step MR mediation analysis was conducted to determine the mediating effects between AFS and aging-GIP.
Results: Earlier AFS was causally associated with lower aging-GIP (β, 0.42; 95%CI, 0.36-0.48). Similar association patterns were observed for longevity (OR, 1.41; 95%CI, 1.11-1.78) and parental lifespan (β, 0.33; 95%CI, 0.28-0.39), while negative causal relationships were found with frailty index (β, −0.30; 95%CI, −0.36 to −0.25), healthspan (β, −0.26; 95%CI, −0.33 to −0.18), and self-rated health (β, −0.32; 95%CI, −0.37 to −0.26). Mediation analysis identified 34 exploratory mediators among 145 candidate mediators between AFS and aging-GIP.
Conclusion: The findings underscore the importance of early sexual health education and suggest implementing targeted interventions to mitigate the adverse effects of early sexual behavior on aging. This approach can promote healthy aging and reduce aging disparities caused by early sexual initiation.

Keywords

Age at First Sexual Intercourse / Aging / Causal Inference / Mendelian Randomization

CRediT authorship contribution statement

Kaixian Wang: Conceptualization, Formal analysis, Methodology, Software, Visualization, Writing - original draft, Writing - review & editing. Yizhan He: Writing - review & editing. Mengyao Yu: Writing - review & editing. Ziming Shao: Writing - review & editing. Zhen Wei: Writing - review & editing. Yingyue Xu: Writing - review & editing. Yazhuo Qi: Writing - review & editing. Wenyu Wang: Writing - review & editing. Xiao Li: Writing - review & editing. Xuehan Ren: Writing - review & editing. Long Sun: Conceptualization, Funding acquisition, Project administration, Supervision, Writing - review & editing. All the authors have read and approved the final version of this manuscript.

Ethics approval

This study used publicly available summary-level genome-wide association study (GWAS) data, with no access to individual-level participant information. Ethical approval for the original GWAS datasets was obtained by the respective study authors and consortia, and all details are reported in their original publications (cited throughout this manuscript).

Funding

The research was supported by the National Natural Science Foundation of China (72574129), and the Humanities and Social Sciences Fund of the Ministry of Education of China (24YJAZH134).

Declaration of Generative AI and AI-assisted technologies in the writing process

Not applicable.

Declaration of Competing Interest

The authors declare no competing interests.

Acknowledgments

The authors are grateful to the participants of all the GWAS used in this manuscript and the investigators who made these GWAS data publicly available.

Appendix A. Supplementary material

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.hcr.2026.100064

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