Proteomic analysis of plasma from 229 subjects revealed a chronic inflammatory state, complement activation, impaired coagulation regulation, and immunosenescence in elderly individuals, with a 25-protein upregulated signature whose expression varied with life-experience and correlated inversely with physical and cognitive condition.
Key Findings
Results
A chronic inflammatory state was identified in the elderly population through proteomic analysis of plasma.
Plasma samples from 229 subjects were analyzed using mass spectrometry-based proteomics.
Three age groups were compared: prepubertal, healthy young adult, and individuals over 75 years old.
The inflammatory condition was confirmed by a parallel Milliplex Luminex assay showing elevated levels of classical pro-inflammatory cytokines in elderly plasma.
Complement activation and impaired regulation of blood coagulation were also identified in the elderly group.
Results
A plasma proteomic signature of aging consisting of 25 upregulated proteins was identified in the elderly group.
The 25 upregulated proteins were identified in the older group (individuals over 75 years old).
The elevated abundance of these proteins, combined with acquired immune aging, was described as constituting 'a plasma proteomic signature of aging.'
The degree of upregulation of these signature proteins varied among elderly subgroups with different life-experiences.
Results
Good physical condition and/or cognitive function in elderly individuals correlated with lower expression of the aging-related proteomic profile.
Three different life-experience subgroups were examined within the cohort of individuals over 75 years old.
A good physical condition and/or cognitive function correlated with a lower expression of the aging-related proteomic profile.
This suggests that lifestyle and functional status may modulate the degree of inflammaging-associated protein upregulation.
Results
The elderly group showed reduced production of antibody light chains, suggesting immunosenescence.
Reduced antibody light chain production was identified through mass spectrometry-based proteomic analysis.
This finding was described as suggesting 'concurrent immunosenescence' in the elderly population.
Immunosenescence features were identified as one of the primary protein variation categories associated with aging.
Results
Several sex-specific differences were identified in the plasma profiles of young donors, but few major differences were observed among elderly individuals.
Sex-specific differences in plasma protein profiles were identified primarily in young donors.
Among elderly individuals, no major sex-based differences were observed.
An exception was an increased level of Pregnancy Zone Protein (PZP) in elderly females compared to elderly males.
Background
Human plasma from older subjects is significantly less effective than plasma from younger individuals when used as a supplement in cell culture media.
This finding is consistent with the heterochronic parabiosis model, in which blood from elderly animals exhibits markedly reduced rejuvenating effects compared to that of young organisms.
This prior evidence motivated the proteomic characterization of plasma across age groups in the current study.
Methods
The study cohort comprised 229 subjects divided into three age groups, including an elderly cohort with three distinct life-experience subgroups.
Total cohort size was 229 subjects.
Age groups included a prepubertal group, a healthy young adult group, and a cohort of individuals over 75 years old.
The over-75 cohort was further subdivided into three subgroups based on different life-experiences.
Both mass spectrometry-based proteomics and Milliplex Luminex assay were used as parallel analytical methods.
Bartolucci M, Utyro O, Muraglia A, Repetto A, Agostini V, Pizzonia M, et al.. (2026). Exploring the impact of age, sex and life experiences on plasma inflammatory profiles through comparative proteomics.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2025.1695213