Late-onset hypogonadism (LOH) is an age-related disease affecting 2–6% of men >40 years old. LOH is a result of reduced testosterone production by the testes and can lead to fatigue, sexual dysfunction and increased susceptibility to metabolic and degenerative diseases. A new study in Nature Aging investigated the mechanisms underlying LOH by assessing the structure and microenvironment of testes on a single-cell level.

Sequencing of primary Sertoli cell lines from two healthy young donors (SCY) and from two individuals with LOH (SCLOH) revealed downregulation of genes for lysosomal acidification in SCLOH compared with SCY, and imaging with pH-sensitive dyes confirmed that SCLOH had substantial deficiencies in lysosomal acidity. Sertoli cells with these deficiencies were named phago/auto-lysosomal dysregulated (PALD) Sertoli cells. “This analysis revealed that abnormal lysosomal acidification in Sertoli cells, leading to lipid droplet accumulation and secretion of pro-inflammatory factors, is a key characteristic of testicular ageing,” says Zhou.