Age-Associated Metabolomic Changes in Human Spermatozoa.

A total of 380 metabolites were identified in human spermatozoa, of which 164 showed significant differences across age groups.

• Study included healthy fertile Arab men across three age groups: young adult (21-30 years, n = 6), late adult (31-40 years, n = 7), and advanced age (41-51 years, n = 5)
• Metabolomics was performed using LC-MS/MS
• Statistical threshold for significance was p < 0.05
• Analyses were performed using MetaboAnalyst-Pro

Principal component analysis, PLS-DA, and sparse PLS-DA consistently demonstrated distinct metabolomic clustering between young adult and advanced age groups.

• Three separate multivariate statistical methods were used: PCA, PLS-DA, and sparse PLS-DA
• All three methods consistently showed distinct clustering
• The clearest separation was observed between young adult (21-30 years) and advanced age (41-51 years) groups
• The late adult group (31-40 years) represented an intermediate profile

L-homocysteine was undetectable in advanced-age spermatozoa, while methyloctadecanoyl-CoA was uniquely abundant in this group.

• L-homocysteine was present in younger age groups but completely absent in the advanced age group (41-51 years)
• Methyloctadecanoyl-CoA was uniquely and abundantly present only in advanced-age spermatozoa
• These metabolites represent the most notable qualitative differences between age groups
• L-homocysteine is involved in oxidative-stress regulation and methylation pathways relevant to sperm function

Biomarker analysis identified 137 potential aging-sperm biomarkers with perfect discriminatory power (AUC = 1).

• All 137 biomarkers achieved AUC = 1, indicating perfect discrimination between age groups
• Upregulated biomarkers in advanced age included pentadecanoyl-CoA, (3S)-3-hydroxylinoleoyl-CoA, CDP-DG(LTE4/20:4(8Z,11Z,14Z,17Z)), and uracil
• Downregulated biomarkers in advanced age included (S)-hydroxyoctanoyl-CoA, DG(22:6/18:4), L-homocysteine, and N-myristoyl serine
• Biomarkers participated in key sperm functional domains including motility, energy metabolism, membrane remodeling, oxidative-stress regulation, and fertilization

Age-related metabolomic changes in spermatozoa affect multiple key functional pathways critical to sperm health.

• Affected pathways included sperm motility, energy metabolism, membrane remodeling, oxidative-stress regulation, and fertilization
• Changes in acyl-CoA species (e.g., pentadecanoyl-CoA, (3S)-3-hydroxylinoleoyl-CoA, methyloctadecanoyl-CoA) suggest disruption of fatty acid metabolism with age
• Loss of L-homocysteine implies disruption of one-carbon metabolism and methylation with advancing age
• Changes in diacylglycerol species (e.g., DG(22:6/18:4)) suggest membrane remodeling alterations
• The authors describe these collective changes as disruption of sperm 'metabolostasis'

The study characterized age-associated sperm metabolomic decline specifically in healthy fertile Arab men, establishing a population-specific baseline.

• All participants were described as healthy and fertile, controlling for confounding pathological infertility
• The study population was specifically Arab men, which the authors note as a defined ethnic cohort
• Total sample size was 18 men (n = 6 young adult, n = 7 late adult, n = 5 advanced age)
• Age range spanned from 21 to 51 years across the three groups