A naturally occurring polyacetylene isolated from carrots promotes health and delays signatures of aging

Carolin Thomas, Reto Erni, Jia Yee Wu, Fabian Fischer, Greta Lamers, Giovanna Grigolon, Sarah J. Mitchell, Kim Zarse, Erick M. Carreira () and Michael Ristow ()
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Carolin Thomas: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16
Reto Erni: Swiss Federal Institute (ETH) Zurich, Vladimir-Prelog-Weg 1-5/10
Jia Yee Wu: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16
Fabian Fischer: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16
Greta Lamers: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16
Giovanna Grigolon: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16
Sarah J. Mitchell: Princeton University
Kim Zarse: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16
Erick M. Carreira: Swiss Federal Institute (ETH) Zurich, Vladimir-Prelog-Weg 1-5/10
Michael Ristow: Swiss Federal Institute (ETH) Zurich, Schorenstrasse 16

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract To ameliorate or even prevent signatures of aging in ultimately humans, we here report the identification of a previously undescribed polyacetylene contained in the root of carrots (Daucus carota), hereafter named isofalcarintriol, which we reveal as potent promoter of longevity in the nematode C. elegans. We assign the absolute configuration of the compound as (3 S,8 R,9 R,E)-heptadeca-10-en-4,6-diyne-3,8,9-triol, and develop a modular asymmetric synthesis route for all E-isofalcarintriol stereoisomers. At the molecular level, isofalcarintriol affects cellular respiration in mammalian cells, C. elegans, and mice, and interacts with the α-subunit of the mitochondrial ATP synthase to promote mitochondrial biogenesis. Phenotypically, this also results in decreased mammalian cancer cell growth, as well as improved motility and stress resistance in C. elegans, paralleled by reduced protein accumulation in nematodal models of neurodegeneration. In addition, isofalcarintriol supplementation to both wild-type C57BL/6NRj mice on high-fat diet, and aged mice on chow diet results in improved glucose metabolism, increased exercise endurance, and attenuated parameters of frailty at an advanced age. Given these diverse effects on health parameters in both nematodes and mice, isofalcarintriol might become a promising mitohormesis-inducing compound to delay, ameliorate, or prevent aging-associated diseases in humans.

Date: 2023
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DOI: 10.1038/s41467-023-43672-7

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