Age-Associated Molecular Changes in Human Hippocampus Subfields as Determined by Quantitative Proteomics.

Area of Science:

• Neuroscience
• Proteomics
• Aging Research

Background:

• The hippocampus undergoes age-related functional and neuronal alterations.
• Significant knowledge gaps exist regarding age-associated proteomic changes in hippocampal subfields.

Purpose of the Study:

• To investigate age-associated proteomic alterations in human hippocampus subfields.
• To identify molecular differences across distinct age groups in the hippocampus.

Main Methods:

• Quantitative proteomics using tandem mass tag (TMT)-based high-resolution mass spectrometry.
• Analysis of formalin-fixed paraffin-embedded hippocampal tissue from 12 healthy individuals across four age groups (1-10, 21-30, 31-40, 81-90 years).

Main Results:

• Lysosome and oxidative phosphorylation pathways were enriched in the 81-90 year group.
• Nervous system development, synaptic plasticity, mRNA splicing, and ETC complex-I activity were enriched in younger age groups.
• Age-related alterations in adult neurogenesis proteins (dentate gyrus) and immune response proteins (cornu ammonis) were observed.

Conclusions:

• This study provides insights into the molecular basis of age-associated proteomic changes in human hippocampal subfields.
• Findings contribute to understanding healthy aging and inform future research on neurodegenerative disorders.