Abstract
Physiological changes associated with aging increase the risk for the development of age-related diseases. This increase is non-specific to the type of age-related disease, although each disease develops through a unique pathophysiologic mechanism. People who age at a faster rate develop age-related diseases earlier in their life. They have an older “biological age” compared to their “chronological age”. Early detection of individuals with accelerated aging would allow timely intervention to postpone the onset of age-related diseases. This would increase their life expectancy and their length of good quality life. The goal of this study was to investigate whether retinal microvascular complexity could be used as a biomarker of biological age. Retinal images of 68 participants ages ranging from 19 to 82 years were collected in an observational cross-sectional study. Twenty of the old participants had age-related diseases such as hypertension, type 2 diabetes, and/or Alzheimer’s dementia. The rest of the participants were healthy. Retinal images were captured by a hand-held, non-mydriatic fundus camera and quantification of the microvascular complexity was performed by using Sholl’s, box-counting fractal, and lacunarity analysis. In the healthy subjects, increasing chronological age was associated with lower retinal microvascular complexity measured by Sholl’s analysis. Decreased box-counting fractal dimension was present in old patients, and this decrease was 2.1 times faster in participants who had age-related diseases (p = 0.047). Retinal microvascular complexity could be a promising new biomarker of biological age. The data from this study is the first of this kind collected in Montenegro. It is freely available for use.




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Acknowledgements
The authors would like to thank to Dr. Nevena Terzić, the director of the Center for Clinical and Laboratory Diagnostics at the Clinical Center of Montenegro, and Ms. Biljana Labović, the head medical laboratory technician, for their outstanding help with the laboratory diagnostics.
Funding
This research was funded by the Ministry of Science, Montenegro (Grant ref. 01–781).
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Conceptualization: NP, MŽ and IRD; Methodology: NP; Formal analysis and investigation: NP, MŽ, IRD, BV, RL, TV, LjR, JE, MR, AAZ, TP; Writing - original draft preparation: NP, SV; Writing - review and editing: NP, MŽ, IRD; Funding acquisition: NP, MŽ, MR; Resources: MR; Supervision: MR.
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Popovic, N., Ždralević, M., Vujosevic, S. et al. Retinal microvascular complexity as a putative biomarker of biological age: a pilot study. Biogerontology 24, 971–985 (2023). https://doi.org/10.1007/s10522-023-10057-8
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DOI: https://doi.org/10.1007/s10522-023-10057-8