Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging

Area of Science:

• Neuroscience
• Proteomics
• Aging Research

Background:

• The orbitofrontal cortex (OFC) is susceptible to aging processes, both normal and pathological.
• Large-scale proteomic studies with layer resolution are lacking for age-related changes in the OFC.

Purpose of the Study:

• To perform a large-scale proteomic analysis of human OFC layer 2/3 to identify age-related protein alterations.
• To investigate the functional implications of identified differentially expressed proteins in the context of aging hallmarks and neurological disorders.

Main Methods:

• High-throughput mass spectrometry-based proteomic analysis was conducted on OFC layer 2/3 samples.
• Samples were obtained from two age groups: 'young' (15-43 years) and 'old' (62-88 years) human males.
• Statistical analysis identified differentially expressed proteins (DEPs) based on p-value and effect size.

Main Results:

• A total of 4193 proteins were detected, with 127 identified as differentially expressed between young and old subjects.
• Key altered biological processes included cell-cell communication (54%), deregulated nutrient sensing (39%), and loss of proteostasis (35%).
• DEPs were significantly associated with neurological disorders such as Alzheimer's disease and schizophrenia.
• Protein co-expression modules remained largely conserved across age groups, indicating functional homeostasis.

Conclusions:

• This study provides a comprehensive proteomic profile of aging in the human OFC layer 2/3.
• Age-related changes in the OFC involve critical cellular functions and are linked to neurological disease.
• The conservation of protein co-expression modules suggests underlying homeostatic mechanisms that maintain brain function during aging.