Aging can be conceptualized as the stochastic accumulation of damage and loss of resilience leading to organism demise. Resilience mechanisms that repair, recycle or replace damaged molecules and organelles are energy-demanding, therefore energy availability is essential to healthy aging. We propose that changes in mitochondrial and energy status regulate RNA splicing and that splicing is a resilience strategy that preserves energetic homeostasis with aging.
References
Ferrucci, L. et al. Aging Cell 19, e13080 (2020).
Kennedy, B. K. et al. Cell 159, 709–713 (2014).
Jang, J. Y., Blum, A., Liu, J. & Finkel, T. J. Clin. Invest. 128, 3662–3670 (2018).
Herzig, S. & Shaw, R. J. Nat. Rev. Mol. Cell Biol. 19, 121–135 (2018).
Wahl, M. C., Will, C. L. & Lührmann, R. Cell 136, 701–718 (2009).
Lee, Y. & Rio, D. C. Annu. Rev. Biochem. 84, 291–323 (2015).
Wang, Z. & Burge, C. B. RNA 14, 802–813 (2008).
Bhadra, M., Howell, P., Dutta, S., Heintz, C. & Mair, W. B. Hum. Genet. 139, 357–369 (2020).
Zeng, L. et al. Aging Cell 19, e13121 (2020).
Harries, L. W. et al. Aging Cell 10, 868–878 (2011).
Holly, A. C. et al. Mech. Ageing Dev. 134, 356–366 (2013).
Lee, B. P. et al. Aging Cell 15, 903–913 (2016).
Rodríguez, S. A. et al. Aging Cell 15, 267–278 (2016).
Tollervey, J. R. et al. Genome Res. 21, 1572–1582 (2011).
Mazin, P. et al. Mol. Syst. Biol. 9, 633 (2013).
Wang, K. et al. Sci. Rep. 8, 10929 (2018).
Gonzalo, S., Kreienkamp, R. & Askjaer, P. Ageing Res. Rev. 33, 18–29 (2017).
Lee, B. P. et al. Biogerontology 20, 649–663 (2019).
Ubaida-Mohien, C. et al. eLife 8, e49874 (2019).
Kourtis, N. & Tavernarakis, N. EMBO J. 30, 2520–2531 (2011).
Ubaida-Mohien, C. et al. Front. Physiol. 10, 312 (2019).
Adelnia, F. et al. Aging Cell 19, e13124 (2020).
Ruetenik, A. & Barrientos, A. Biochim. Biophys. Acta 1847, 1434–1447 (2015).
Rhoads, T. W. et al. Cell Metab. 27, 677–688 (2018).
Lee, B. P. et al. Exp. Gerontol. 128, 110736 (2019).
Heintz, C. et al. Nature 541, 102–106 (2017).
Matsumoto, E. et al. Biochem. J. 477, 2237–2248 (2020).
Kulkarni, A. S. et al. Aging 12, 19852–19866 (2020).
Salminen, A. & Kaarniranta, K. Ageing Res. Rev. 11, 230–241 (2012).
Egesipe, A. L. et al. NPJ Aging Mech. Dis. 2, 16026 (2016).
Tumasian, R. A. III et al. Nat. Commun. 12, 2014 (2021).
Maracchioni, A. et al. J. Neurochem. 100, 142–153 (2007).
Heyd, F., Carmo-Fonseca, M. & Möröy, T. J. Biol. Chem. 283, 19636–19645 (2008).
Liu, Y. et al. Sci. Rep. 7, 5754 (2017).
Christofk, H. R. et al. Nature 452, 230–233 (2008).
Salminen, A., Kauppinen, A. & Kaarniranta, K. Cell. Mol. Life Sci. 72, 3897–3914 (2015).
Farina, A. R. et al. J. Exp. Clin. Cancer Res. 39, 110 (2020).
Acknowledgements
This research was supported by the Intramural Research Program of the National Institute on Aging, NIH.
Author information
Authors and Affiliations
Contributions
L.F. conceived the axis model, and all authors participated in identifying relevant literature, refining the model and writing and editing the Comment.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Rights and permissions
About this article
Cite this article
Ferrucci, L., Wilson, D.M., Donegà, S. et al. The energy–splicing resilience axis hypothesis of aging. Nat Aging 2, 182–185 (2022). https://doi.org/10.1038/s43587-022-00189-w
Published:
Issue Date:
DOI: https://doi.org/10.1038/s43587-022-00189-w
- Springer Nature America, Inc.
This article is cited by
-
Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more?
Cellular and Molecular Life Sciences (2024)
-
Transcriptomic reprogramming for neuronal age reversal
Human Genetics (2023)