Cellular and molecular functions of long noncoding RNAs in testis, aging and diseases.

Abstract

Reproductive aging is an emerging global health concern, projected to become the third most significant health issue in the near future, according to the World Health Organization. This complex process is driven by molecular and cellular changes, including alterations in DNA, RNA, and protein expression. Among non-coding RNAs (ncRNAs), long non-coding RNAs (lncRNAs) have been increasingly recognized for their regulatory roles in spermatogenesis and their potential contributions to aging and testicular diseases. This review examines the functions of lncRNAs in testicular biology, focusing on their gene-regulatory roles, isoform diversity, subcellular localization, and interactions with key molecular components. While research has historically prioritized protein-coding genes, the extensive ncRNA landscape suggests a broader regulatory network influencing reproductive health. Many testis-specific lncRNAs exhibit conserved sequences, modular structures, and repeat-rich elements, which contribute to their functional significance. Dysregulation of these lncRNAs has been implicated in pathological conditions such as testicular cancer, highlighting their potential as biomarkers and therapeutic targets. Understanding the dynamic roles of lncRNAs in testicular function, aging, and disease is essential for advancing reproductive medicine. This study provides insights into the complex interplay between lncRNAs and reproductive aging, emphasizing their significance in testis-specific processes and associated disorders.