THE ROLE OF SENESCENCE-ASSOCIATED INTERFERON IN AGE-RELATED INFLAMMATION

Sep 29, 2026

Age-related inflammation is driven by inflammaging: persistent inflammation paired with heightened immune reactivity to pathogens. This study investigates how senescent monocytes promote inflammaging and tests therapies targeting senescence and related interferon signaling. An irradiation-induced senescence model in THP-1 monocytes used DIA mass spectrometry proteomics and LPS-stimulated cytokine assays. Circulating monocytes from 94 adults aged 22–89 in the GESTALT cohort linked senescence-associated proteins with IFN signatures, CRP, and aging phenotypes. Senescent monocytes showed strong interferon-related proteome remodeling and potentiated LPS cytokine responses; interventions reduced these effects.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages1

Reading Time3 min

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Abstract

Senescent monocytes and inflammaging

Experimental model and proteomic profiling

LPS response and therapeutic targeting

Clinical associations and biomarkers

Innovation in Aging, 2025, Vol. 9, No. S2 987 Abstract citation ID: igaf122.3332 THE ROLE OF SENESCENCE-ASSOCIATED INTERFERON IN AGE-RELATED INFLAMMATION Mansi Shrivastava1, Reema Banarjee2, Bradley Olinger2, Linna Cui2, Amit Dey2, Myriam Gorospe2, and Nathan Basisty2, 1. National Institute on Aging, Baltimore, Maryland, United States, 2. National Institute on Aging, Bethesda, Maryland, United States Inflammaging, age-related deterioration of immune function, features persistent inflammation alongside an exacerbated immune response to pathogens. Senescent monocytes accumulate with age and release harmful proteins, potentially driving hyperinflammation. This study explores how senescent monocytes contribute to inflammaging and evaluates therapeutic interventions targeting these cells. Using an irradiation-induced senescence model in THP-1 monocytes, we analyzed the proteomic changes via data-independent acquisition (DIA) mass spectrometry. We assessed the impact of senescence on pathogen response by measuring LPS-induced inflammatory cytokines in senescent and non-senescent cells using a Mesoscale kit. Additionally, we tested various compounds for their ability to modulate inflammation and evaluated inflammatory signatures in monocytes. Finally, we examined proteomic profiles of circulating monocytes from 94 individuals aged 22-89 in the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) study of aging to identify clinical associations between senescence and IFN signatures and aging phenotypes in vivo. Senescent THP-1 monocytes exhibited significant proteome remodeling, with increased 359 IFN-related proteins, including STAT1, OAS1, OAS2, MX1, and ISG15, while 1355 decreased proteins. Moreover, when stimulated with LPS, senescent monocytes exhibited a highly potentiated inflammatory cytokine response, including interleukins and IFN-ƴ, driving inflammaging and susceptibility. Notably, interventions targeting senescence or IFN signaling reduced these inflammatory responses. Further, the proteomic analysis of circulating monocytes in the GESTALT cohort showed that 27 senescence-associated proteins, correlated with CRP, were identified as potential biomarkers, highlighting systemic inflammation. These findings highlight senescence-associated IFN signaling as a key driver of inflammaging and suggest potential therapeutic strategies to mitigate age-related immune dysregulation.

FAQs

What role do senescent monocytes play in inflammaging?

Senescent monocytes accumulate with age and release harmful proteins, potentially driving hyperinflammation. This study shows they contribute to inflammaging via interferon-related signaling changes and stronger inflammatory cytokine responses after LPS stimulation.

How was senescence modeled and analyzed in the study?

The work used an irradiation-induced senescence model in THP-1 monocytes. Proteomic changes were measured by data-independent acquisition (DIA) mass spectrometry, and inflammatory responses were assessed using LPS-induced cytokines.

Which therapeutic targets were tested, and what was the result?

The study tested compounds and interventions targeting senescence or IFN signaling. These interventions reduced the senescent cells’ inflammatory cytokine responses, indicating a causal role for senescence-associated IFN signaling in inflammaging.

Sep 29, 2026

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