Open Research Projects, Research

Ultra-sensitive systemic inflammatory signatures of age-related multimorbidity in naturally aged mice

Prinicipal Investigator

Prof. Dr. Eicke Latz

Scientific interest within the context of the graduate college

This project addresses a central aim of the EKFS Graduate School: to identify systemic signals that precede, accompany, and potentially predict age-related disease. Rather than studying one organ in isolation, the unbiased ageing-health project asks whether a measurable low-grade inflammatory state in blood marks broader multimorbidity in ageing. By linking ultra-sensitive circulating inflammatory profiles to visible, metabolic, neoplastic, ocular, and microbiome-associated ageing phenotypes in mice, the study fits the prevention focus of EKFS and can nominate biomarker signatures relevant to early risk stratification in humans.

Project description

Chronic low-grade inflammation (“inflammaging”) is increasingly viewed as a shared upstream process across many late-life disorders, yet it remains unclear whether one measurable systemic inflammatory state tracks the breadth of spontaneous age-related pathology within an individual. Naturally aged C57BL/6J mice provide a useful discovery model because genetically identical animals nevertheless develop heterogeneous phenotypes including neoplasia, metabolic dysfunction and hepatic steatosis, coat deterioration with alopecia and hair greying, cataract, and marked shifts in the gut microbiome. This EKFS proposal defines a smaller and more feasible student subproject from a large unbiased murine ageing study run in the Latz lab centered on one tractable question: are ultra-sensitive blood inflammatory signatures linked to these age-related phenotypes? Using the Alamar Biosciences NULISAseq Mouse Panel 120, a murine multiplex assay with 120+ protein targets, attomolar sensitivity, and low-input workflows, the student will analyze archived serum or plasma from an existing aged mouse cohort and integrate these data with available pathology and microbiome readouts. The overall goal is to derive a simple systemic inflammaging score and test whether it identifies mice with a higher burden of spontaneous age-related disease.

Aim 1 / WP1: Generate ultra-sensitive systemic inflammatory profiles in naturally aged mice. Archived serum or plasma from naturally aged C57BL/6J mice will be analyzed using the Alamar Biosciences NULISAseq Mouse Panel 120. This work package is intentionally focused and technically feasible for a medical student because it relies on existing samples and an established multiplex platform rather than de novo animal experimentation. After standard quality control and normalization, the student will quantify circulating cytokines, chemokines, and related inflammatory mediators and construct a compact inflammaging score based on the most reproducible markers. In addition to describing the overall inflammatory landscape of the cohort, the analysis will identify individual proteins or small marker combinations that segregate mice with low versus high age-related disease burden.

Aim 2 / WP2: Test whether systemic inflammatory signatures are linked to age-related pathologies and microbiome states. The inflammatory profiles generated in Aim 1 will be integrated with existing phenotypic readouts from the same animals. Priority phenotypes will include neoplastic lesions, metabolic syndrome-like traits (for example body weight, glucose dysregulation and/or steatosis where available), coat changes such as alopecia and hair greying, cataract, and microbiome features derived from fecal profiling. The student will establish a multimorbidity index and determine whether the systemic inflammaging score, or selected individual proteins, associates with single phenotypes and with cumulative disease burden across organs. This analysis will provide an experimentally manageable first step toward identifying blood-based markers that report organismal ageing trajectories and will nominate high-priority biomarker-pathology links for subsequent mechanistic follow-up in the larger parent project.

Application details

References

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  5. Schaum N, Lehallier B, Hahn O, Pálovics R, Hosseinzadeh S, Lee SE, Sit R, Lee DP, Losada PM, Zardeneta ME, Fehlmann T, Webber JT, McGeever A, Calcuttawala K, Zhang H, Berdnik D, Mathur V, Tan W, Zee A, Tan M; Tabula Muris Consortium; Pisco AO, Karkanias J, Neff NF, Keller A, Darmanis S, Quake SR, Wyss-Coray T. Ageing hallmarks exhibit organ-specific temporal signatures. Nature. 2020; 583(7817): 596-602.