Proteomic Signatures of Aging Across Human and Animal Tissues: Large-Scale Data Analysis of Protein Modifications and Functional Outcomes

David Aphkhazava; Archil Chirakadze; Levan Gulua; Nodar Sulashvili; Lolita Shengelia; Hanshika Verma; Tamar Okropiridze

Authors

David Aphkhazava PhD, Full Professor of Biochemistry at Alte university, Tbilisi, Georgia; Invited Lecturer (Professor) of Biochemistry, University of Georgia, Tbilisi Georgia, Full professor of Biochemistry Georgian National University SEU, Tbilisi Georgia , Invited Lecturer (Professor) of Biophysics and Microbiology, Georgian Technical University, Tbilisi, Georgia. Orcid: https://orcid.org/0000-0001-6216-6477
Archil Chirakadze PhD, Georgian Techical University, Ivane Javakhishvili Tbilisi State University
Levan Gulua PhD, Professor, Head of bachelor program of Biomedicine at University of Georgia, Tbilisi, Georgia.
Nodar Sulashvili MD, PhD, Doctor of Pharmaceutical and Pharmacological Sciences In Medicine, Invited Lecturer (Professor) of Scientific Research-Skills Center at Tbilisi State Medical University; Professor of Medical and Clinical Pharmacology of International School of Medicine at Alte University; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU, Associate Affiliated Professor of Medical Pharmacology of Faculty of Medicine at Sulkhan-Saba Orbeliani University; Associate Professor of Medical Pharmacology at School of Medicine at David Aghmashenebeli University of Georgia; Associate Professor of Biochemistry and Pharmacology Direction of School of Health Sciences at the University of Georgia. Associate Professor of Pharmacology of Faculty of Dentistry and Pharmacy at Tbilisi Humanitarian Teaching University; Tbilisi, Georgia; Orcid: https://orcid.org/0000-0002-9005-8577.
Lolita Shengelia PhD, Invited lecturer of Georgian National University, Tbilisi, Georgia; Invited lecturer of Georgian American University, Tbilisi, Georgia
Hanshika Verma University of Georgia, Tbilisi, Georgia
Tamar Okropiridze Doctor of Medical Sciences, Professor at Alte University, Tbilisi, Georgia

Keywords:

Aging, Proteomics, Post-translational modifications, Cross-species analysis, Protein aggregation, Mitochondrial dysfunction, Neurodegeneration, Comparative biology

Abstract

Aging is a universal biological process characterized by progressive functional decline and increased susceptibility to disease. While genomic and transcriptomic changes have been extensively studied, proteomic alterations — including abundance shifts, misfolding, aggregation, and post-translational modifications (PTMs) — provide a more direct reflection of cellular function and dysfunction during aging. In this study, we conducted a large-scale comparative proteomic analysis across human and animal tissues, including brain, liver, skeletal muscle, and kidney, to identify conserved and tissue-specific protein signatures of aging. Our analysis revealed that proteins involved in proteostasis, mitochondrial metabolism, and synaptic transmission undergo age-dependent abundance changes and PTMs such as oxidation, glycation, and ubiquitination. Statistical evaluation with robust sample sizes demonstrated significant differences (p < 0.01) in protein stability and modification patterns between young and aged tissues, supported by error-bar–based confidence intervals. Comparative cross-species analysis highlighted conserved proteomic shifts in energy metabolism and cytoskeletal proteins, while human-specific changes were enriched in proteins related to neurodegeneration and immune response. These findings provide an integrative framework for understanding how proteomic aging signatures manifest across tissues and species, and they underscore the role of protein modifications in the onset of age-related functional decline.

Proteomic Signatures of Aging Across Human and Animal Tissues: Large-Scale Data Analysis of Protein Modifications and Functional Outcomes

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