Introduction Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. Biological age can be estimated by DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA). Low levels of serum selenium, selenoprotein P (SELENOP), and the selenocysteine-containing glutathione peroxidase 3 (GPx3) are associated with adverse health outcomes and selenium supplementation is discussed as an anti-aging intervention. Methods In this study we analyzed 1,568 older participants from the Berlin Aging Study II (mean age +/- SD: 68.8 +/- 3.7 years, 51% women). DNAmA was estimated from genome-wide DNA methylation data using the Horvath, GrimAge, and DunedinPACE algorithms. Serum selenium levels were measured by total reflection X-ray fluorescence (TXRF) spectroscopy. SELENOP was measured by ELISA and GPx3 was derived from a larger set of mass spectrometry proteomics data. Results Participants with deficient serum selenium levels (<90μg/L) had a higher rate of biological aging (DunedinPACE, p=0.01, n=865). This association remained statistically significant after adjustment for age, sex, BMI, smoking, and genetic ancestry (β=-0.02, SE=0.01, 95%CI: -0.034 to -0.004, n=757). Compared to the highest quartile, participants in the lowest quartile of SELENOP levels showed an accelerated biological aging rate (DunedinPACE, β=-0.03, SE=0.01, 95%CI: -0.051 to -0.008, n=740, fully adjusted model). Similarly, after adjustment for covariates, accelerated biological age was found in participants within the lowest GPx3 quartile compared to participants in the fourth quartile (DunedinPACE, p=<0.001 and GrimAge, p<0.001). Conclusion Our study suggests that low levels of selenium biomarkers are associated with accelerated biological aging measured as DNAmA. This effect was not substantially changed after adjustment for known covariates.

LS holds shares of selenOmed GmbH, a company involved in Se status assessment; no other relationships or activities that could appear to have influenced the submitted work are indicated. Other authors: none.

This work was supported by grants of the Deutsche Forschungsgemeinschaft (grant number 460683900 to ID and LB, and CRC/TR 296 "LocoTact" to LS), the ERC (as part of the "Lifebrain" project to LB), and the Cure Alzheimer's Fund (as part of the "CIR-CUITS" consortium to LB), the German Federal Ministry of Education and Research as part of the National Research Initiative 'Mass Spectrometry in Systems Medicine' (MSCoreSys), under grant agreement number 01EP2201 (to MR) and 16LW0239K (to MM), the Berlin University Alliance (BUA Link Lab, 501_Massenspektrometrie, 501_Linklab), as well as the German Cancer Consortium (DKTK) under grant BE01 1020000483 (to MR). C.M.L. was supported by the Heisenberg program of the German Research Foundation (DFG; LI 2654/4-1). This article uses data from the Berlin Aging Study II (BASE-II). BASE-II was supported by the German Federal Ministry of Education and Research under grant numbers #01UW0808; #16SV5536K, #16SV5537, #16SV5538, #16SV5837, #01GL1716A, and #01GL1716B.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Ethics Committee of the Charite - Universitaetsmedizin Berlin gave ethical approval for tis work (approval numbers EA2/029/09 and EA2/144/16).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Due to concerns for participant privacy, data are available only upon reasonable request. Please contact Ludmila Mueller, scientific coordinator, at lmueller@mpib-berlin.mpg.de, for additional information.