Perspectives on biomarkers of reproductive aging for fertility and beyond

Abstract

Reproductive aging, spanning an age-related functional decline in the female and male reproductive systems, compromises fertility and leads to a range of health complications. In this Perspective, we first introduce a comprehensive framework for biomarkers applicable in clinical settings and discuss the existing repertoire of biomarkers used in practice. These encompass functional, imaging-based and biofluid-based biomarkers, all of which reflect the physiological characteristics of reproductive aging and help to determine the reproductive biological age. Next, we delve into the molecular alterations associated with aging in the reproductive system, highlighting the gap between these changes and their potential as biomarkers. Finally, to enhance the precision and practicality of assessing reproductive aging, we suggest adopting cutting-edge technologies for identifying new biomarkers and conducting thorough validations in population studies before clinical applications. These advancements will foster improved comprehension, prognosis and treatment of subfertility, thereby increasing chances of preserving reproductive health and resilience in populations of advanced age. Measuring reproductive aging in humans remains challenging. In this Perspective, Wang et al. summarize biomarkers for reproductive aging in clinical use, discuss age-linked molecular changes related to reproductive aging that could potentially serve as future biomarkers and highlight unresolved challenges and upcoming opportunities in the field.