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Combinatorial interventions in aging

Nature Aging volume 3, pages 1187–1200 (2023)Cite this article

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Abstract

Insight on the underlying mechanisms of aging will advance our ability to extend healthspan, treat age-related pathology and improve quality of life. Multiple genetic and pharmacological manipulations extend longevity in different species, yet monotherapy may be relatively inefficient, and we have limited data on the effect of combined interventions. Here we summarize interactions between age-related pathways and discuss strategies to simultaneously retard these in different organisms. In some cases, combined manipulations additively increase their impact on common hallmarks of aging and lifespan, suggesting they quantitatively participate within the same pathway. In other cases, interactions affect different hallmarks, suggesting their joint manipulation may independently maximize their effects on lifespan and healthy aging. While most interaction studies have been conducted with invertebrates and show varying levels of translatability, the conservation of pro-longevity pathways offers an opportunity to identify ‘druggable’ targets relevant to multiple human age-associated pathologies.

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Fig. 1: Hierarchical frameworks for aging interaction analysis.
Fig. 2: Select interactions between mechanisms or hallmarks of aging.
Fig. 3: An example of interactions within a hallmark: mitochondria-related mechanisms.
Fig. 4: Overview of interactions between different processes (hallmarks) of aging.

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Acknowledgements

This work was supported by the National Institute of General Medical Sciences R35 GM146869 (to A.A.P.), NIA R00 AG057792 (to A.A.P.), NIA R03 AG075651 (to A.A.P.), NIA P30 AG024827 pilot grant (to A.A.P.), Richard King Mellon Foundation award (to A.A.P.), NIA R01 AG059563 (to M.T.) and NIA R01 AG069639 (to M.T.).

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Authors and Affiliations

  1. Aging Institute of UPMC and the University of Pittsburgh, Pittsburgh, PA, USA

    Andrey A. Parkhitko

  2. Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA

    Elizabeth Filine

  3. Department of Ecology, Evolution and Organismal Biology, Brown University, Providence, RI, USA

    Marc Tatar

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  1. Andrey A. Parkhitko
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  2. Elizabeth Filine
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A.A.P., E.F. and M.T. wrote the manuscript and prepared the figures.

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Correspondence to Andrey A. Parkhitko or Marc Tatar.

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Parkhitko, A.A., Filine, E. & Tatar, M. Combinatorial interventions in aging. Nat Aging 3, 1187–1200 (2023). https://doi.org/10.1038/s43587-023-00489-9

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