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Toward precision interventions and metrics of inflammaging

Nature Aging volume 5, pages 1441–1454 (2025)Cite this article

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Abstract

Inflammaging describes a chronic, systemic, low-grade inflammatory state that is recognized as a major risk factor for age-related diseases (ARDs) and a pivotal convergence point of multiple biological mechanisms involved in aging. Here, we discuss the heterogeneity of inflammaging, proposing that it emerges as a consequence of each individual’s lifelong exposures to inflammatory stimuli, shaped by a unique combination of genetics, lifestyle, socioeconomic conditions and environmental factors such as infections and pollution. Through this lens, we then discuss measuring inflammaging, describing the development of inflammatory clocks that quantify inflammatory age and show strong associations with ARD incidence as well as how other aging clocks intersect with inflammaging. Finally, we consider interventions that may counteract inflammaging, including nutritional interventions, physical activity and gerotherapies such as senolytics. We propose that deepening our knowledge of the individual nature of inflammaging stands to enhance our understanding of personalized aging trajectories and inform precision interventions.

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Fig. 1: Main sources and mechanisms underlying personalized inflammaging.
Fig. 2: Local explainability of AI-based SImAge clock illustrated by waterfall plots.
Fig. 3: Personalized anti-inflammaging treatments.
Fig. 4: Personalized explainable inflammaging clocks.

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Acknowledgements

This work was supported by funding from the Italian Ministry of Health ‘Ricerca Corrente’ to IRCCS INRCA and by Next Generation EU, in the context of the National Recovery and Resilience Plan, Investment PE8, Project Age-It: ‘Ageing Well in an Ageing Society’ to F.O. The views and opinions expressed are only those of the authors and do not necessarily reflect those of the European Union or the European Commission. Neither the European Union nor the European Commission can be held responsible for them. This work was also supported by the Ministry of Economic Development of the Russian Federation (grant no. 139-15-2025-004 dated 17 April 2025, agreement identifier 000000С313925P3X0002) to M.I. We thank M. Marzio (IRCCS INRCA, Ancona, Italy) for drawing Figs. 1, 3 and 4; I. Yusipov and A. Kalyakulina (Lobachevsky University, Nizhny Novgorod, Russia) for preparing Fig. 2 and L.S. Jurado-Medina (University of Bologna, Bologna, Italy) for checking the text and preparing the reference list.

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Authors and Affiliations

  1. Institute of Biogerontology, Lobachevsky University, Nizhny Novgorod, Russia

    Claudio Franceschi & Mikhail Ivanchenko

  2. Research Center in Artificial Intelligence, Lobachevsky University, Nizhny Novgorod, Russia

    Claudio Franceschi & Mikhail Ivanchenko

  3. Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy

    Fabiola Olivieri

  4. Advanced Technology Center for Aging Research, IRCCS INRCA, Ancona, Italy

    Fabiola Olivieri

  5. Longevity Institute of Russian Research Surgery Center, Moscow, Russia

    Alexey Moskalev

  6. Department of Medical and Surgical Sciences (DIMEC), University of Bologna, Bologna, Italy

    Aurelia Santoro

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  1. Claudio Franceschi
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Contributions

C.F. and A.S. conceived the Review and wrote the first draft of the manuscript. F.O., A.M. and M.I. provided constructive input and wrote additional sections in subsequent revisions of the manuscript. All authors approved the final version of the Review and its tables, box and figures.

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Correspondence to Fabiola Olivieri or Aurelia Santoro.

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Franceschi, C., Olivieri, F., Moskalev, A. et al. Toward precision interventions and metrics of inflammaging. Nat Aging 5, 1441–1454 (2025). https://doi.org/10.1038/s43587-025-00938-7

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