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Peer-reviewedCC BY-NC-ND 4.0NPJ Aging

Reproductive behaviors, genetic susceptibility and accelerated aging risk

  • Jinghui Zhong1
  • Deyan Kong2
  • Genpei Luo3
  • Yiran Dong1
  • Mingming Yu1,4
  • Pan Zhang1
  • Yingjie Xu1
  • Xinfeng Liu1,5
  • Wen Sun1
5 affiliations
  1. 1Department of Neurology, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui China
  2. 2Department of Neurology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi China
  3. 3Department of Neurology, Dongguan People’s Hospital, Dongguan, China
  4. 4Department of Neurology, The 901st Hospital of Chinese People’s Liberation Army Joint Logistic Support Force, Hefei, Anhui China
  5. 5Department of Neurology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
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Abstract

We examined the associations of reproductive behaviors and genetic susceptibility with aging indicators among female participants in the UK Biobank. Reproductive behaviors included the number of children ever born (NEB), age at first birth (AFB), age at last birth (ALB), and span of years of births (SYB). Aging indicators included frailty, PhenoAge acceleration, KDM-BA acceleration, and brain age difference (BrainAGE-diff). In multivariable analyses, reproductive behaviors showed nonlinear associations with aging indicators. Women with NEB of 2–3 had lower frailty risk, PhenoAge acceleration, KDM-BA acceleration, and BrainAGE-diff. Later AFB and later ALB were also associated with lower levels of several aging indicators, whereas longer SYB was associated with higher frailty risk and PhenoAge acceleration. Mendelian randomization suggested that genetically predicted higher NEB was associated with higher frailty risk and greater PhenoAge acceleration, while genetically predicted later AFB was associated with lower frailty risk and lower PhenoAge and KDM-BA acceleration. Joint analyses showed that high polygenic risk scores combined with NEB > 3, AFB < 25 years, or SYB ≥ 6 years were associated with higher aging burden, although multiplicative interactions were not statistically significant.

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Cite

BibTeXRIS
BibTeX
@article{zhong2026reproductive,
  title = {{Reproductive behaviors, genetic susceptibility and accelerated aging risk}},
  author = {Jinghui Zhong and Deyan Kong and Genpei Luo and Yiran Dong and Mingming Yu and Pan Zhang and Yingjie Xu and Xinfeng Liu and Wen Sun},
  journal = {NPJ Aging},
  year = {2026},
  month = jul,
  doi = {10.1038/s41514-026-00440-3},
  url = {https://doi.org/10.1038/s41514-026-00440-3},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Reproductive behaviors, genetic susceptibility and accelerated aging risk
AU  - Jinghui Zhong
AU  - Deyan Kong
AU  - Genpei Luo
AU  - Yiran Dong
AU  - Mingming Yu
AU  - Pan Zhang
AU  - Yingjie Xu
AU  - Xinfeng Liu
AU  - Wen Sun
PY  - 2026
DA  - 2026/07/08
JO  - NPJ Aging
DO  - 10.1038/s41514-026-00440-3
UR  - https://doi.org/10.1038/s41514-026-00440-3
AB  - We examined the associations of reproductive behaviors and genetic susceptibility with aging indicators among female participants in the UK Biobank. Reproductive behaviors included the number of children ever born (NEB), age at first birth (AFB), age at last birth (ALB), and span of years of births (SYB). Aging indicators included frailty, PhenoAge acceleration, KDM-BA acceleration, and brain age difference (BrainAGE-diff). In multivariable analyses, reproductive behaviors showed nonlinear associations with aging indicators. Women with NEB of 2–3 had lower frailty risk, PhenoAge acceleration, KDM-BA acceleration, and BrainAGE-diff. Later AFB and later ALB were also associated with lower levels of several aging indicators, whereas longer SYB was associated with higher frailty risk and PhenoAge acceleration. Mendelian randomization suggested that genetically predicted higher NEB was associated with higher frailty risk and greater PhenoAge acceleration, while genetically predicted later AFB was associated with lower frailty risk and lower PhenoAge and KDM-BA acceleration. Joint analyses showed that high polygenic risk scores combined with NEB > 3, AFB < 25 years, or SYB ≥ 6 years were associated with higher aging burden, although multiplicative interactions were not statistically significant.
SN  - 2731-6068
ER  -