A bile acid could explain how calorie restriction slows ageing

Sinclair, David A.

doi:10.1038/d41586-024-04062-1

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18 December 2024

A bile acid could explain how calorie restriction slows ageing

Could lithocholic acid, a compound produced when gut bacteria process bile, be the missing link between a low-calorie diet and its age-defying effects? Experiments in mice, flies and nematode worms provide clues.

David A. Sinclair ORCID: http://orcid.org/0000-0002-9936-436X⁰

David A. Sinclair
1. David A. Sinclair is in the Department of Genetics, Paul F. Glenn Center for Biology of Aging Research, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
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Across the ancient world, physicians from Greece to China touted the health benefits of bile and fasting. Today, the focus is on regular meals and exercise, but perhaps those ancient doctors were onto something. In two papers in Nature, Qu and colleagues¹^,² make a compelling case that a component of bile called lithocholic acid (LCA) triggers many of the age-defying and potentially lifespan-extending health benefits of low-calorie diets.

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doi: https://doi.org/10.1038/d41586-024-04062-1

References

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Competing Interests

D.A.S. is a co-founder, consultant, board member and equity owner of Galilei Biosciences and MetroBiotech, companies working to treat diseases with SIRT6 activators and NAD boosters, respectively. He is also an equity owner of Tally Health, a DNA biomarker company. Other activities are listed at sinclair.hms.harvard.edu

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[1] Qu, Q. et al. Nature https://doi.org/10.1038/s41586-024-08329-5 (2024).
Article Google Scholar

[2] Qu, Q. et al. Nature https://doi.org/10.1038/s41586-024-08348-2 (2024).
Article Google Scholar

[3] McCay, C. M., Crowell, M. F. & Maynard, L. A. J. Nutrition 10, 63–79 (1935).
Article Google Scholar

[4] Liao, C.-Y., Rikke, B. A., Johnson, T. E., Diaz, V. & Nelson, J. F. Aging Cell 9, 92–95 (2010).
Article PubMed Google Scholar

[5] Mattison, J. A. et al. Nature Commun. 8, 14063 (2017).
Article PubMed Google Scholar

[6] Kimura, K. D., Tissenbaum, H. A., Liu, Y. & Ruvkun, G. Science 277, 942–946 (1997).
Article PubMed Google Scholar

[7] Lin, S.-J., Defossez, P.-A. & Guarente, L. Science 289, 2126–2128 (2000).
Article PubMed Google Scholar

[8] Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O. & Sinclair, D. A. Nature 423, 181–185 (2003).
Article PubMed Google Scholar

[9] Gerisch, B. et al. Proc. Natl Acad. Sci. USA 104, 5014–5019 (2007).
Article PubMed Google Scholar

[10] Staats, S. et al. Mol. Nutr. Food Res. 62, e1800424 (2018).
Article PubMed Google Scholar

[11] Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J. & Schoonjans, K. Nature Rev. Drug Discov. 7, 678–693 (2008).
Article PubMed Google Scholar

[12] Bárcena, C. et al. Nature Med. 25, 1234–1242 (2019).
Article PubMed Google Scholar

[13] Chen, D. & Guarente, L. Trends Mol. Med. 13, 64–71 (2007).
Article PubMed Google Scholar

[14] Martin-Montalvo, A. et al. Nature Commun. 4, 2192 (2013).
Article PubMed Google Scholar

[15] Howitz, K. T. et al. Nature 425, 191–196 (2003).
Article PubMed Google Scholar

[16] Mercken, E. M. et al. Aging Cell 13, 787–796 (2014).
Article PubMed Google Scholar

[17] Krueger, J. G. et al. PLoS ONE 10, e0142081 (2015).
Article PubMed Google Scholar

[18] Najt, C. P. et al. Mol. Cell 77, 810–824 (2020).
Article PubMed Google Scholar

[19] Song, M. et al. Anim. Nutr. 7, 365–375 (2021).
Article PubMed Google Scholar

[20] Kawasumi, H. et al. Oncology 45, 192–196 (1988).
Article PubMed Google Scholar

A bile acid could explain how calorie restriction slows ageing

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Head of Rare Circulating Cells Core Facility

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Jobs

Nanjing Forestry University Recruits Metasequoia Scholars and Metasequoia Talents Worldwide

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