Rodrigo Mohallem | Search PubMed

PubMed2026

Urine and Serum Proteome and Lipidome Analysis of Naturally Aging Feline Species.

Aging in companion animals such as cats closely relates to human aging in environmental exposures and disease manifestation, providing a valuable model for identifying biomarkers of age-associated decline. This study provides a combined proteomic and lipidomic analysis of serum and urine from naturally aging domestic cats aged 3.8-16 years, grouped as adult, old, and senior, to identify age-related molecular changes across biofluids. Label-free quantitative proteomics identified 901 urinary and 238 serum proteins, with 75 urinary proteins significantly altered with age that are linked to kidney disease, hypertension, neurodegeneration, and metabolic disorders. In contrast, only six serum proteins differed significantly between adult and old/senior cats, including decreased Apolipoprotein A-I (APOA1) in seniors, a protein linked with cognitive function in aging. Untargeted lipidomics revealed increases in specific serum triacylglycerols, phosphatidylcholines (PCs), and sphingomyelins, while urinary lipid profiles showed limited age-related changes, with some PCs decreasing, and diacylglycerols increasing with age. These results demonstrate distinct systemic and renal molecular remodeling during feline aging and highlight the utility of integrated omics analyses of biological fluids for identifying molecular alterations relevant to both feline and human aging.

Animals↗

PubMed2024

Molecular Signatures of Neurodegenerative Diseases Identified by Proteomic and Phosphoproteomic Analyses in Aging Mouse Brain.

A central hallmark of neurodegenerative diseases is the irreversible accumulation of misfolded proteins in the brain by aberrant phosphorylation. Understanding the mechanisms underlying protein phosphorylation and its role in pathological protein aggregation within the context of aging is crucial for developing therapeutic strategies aimed at preventing or reversing such diseases. Here, we applied multi-protease digestion and quantitative mass spectrometry to compare and characterize dysregulated proteins and phosphosites in the mouse brain proteome using three different age groups: young-adult (3-4 months), middle-age (10 months), and old mice (19-21 months). Proteins associated with senescence, neurodegeneration, inflammation, cell cycle regulation, the p53 hallmark pathway, and cytokine signaling showed significant age-dependent changes in abundances and level of phosphorylation. Several proteins implicated in Alzheimer's disease (AD) and Parkinson's disease (PD) including tau (Mapt), Nefh, and Dpysl2 (also known as Crmp2) were hyperphosphorylated in old mice brain suggesting their susceptibility to the diseases. Cdk5 and Gsk3b, which are known to phosphorylate Dpysl2 at multiple specific sites, had also increased phosphorylation levels in old mice suggesting a potential crosstalk between them to contribute to AD. Hapln2, which promotes α-synuclein aggregation in patients with PD, was one of the proteins with highest abundance in old mice. CD9, which regulates senescence through the PI3K-AKT-mTOR-p53 signaling was upregulated in old mice and its regulation was correlated with the activation of phosphorylated AKT1. Overall, the findings identify a significant association between aging and the dysregulation of proteins involved in various pathways linked to neurodegenerative diseases with potential therapeutic implications.

Animals↗