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

• Published in: Nature communications 2023-12, Vol.14 (1), p.8142-8142, Article 8142
• Main Authors: Thomas, Carolin, Erni, Reto, Wu, Jia Yee, Fischer, Fabian, Lamers, Greta, Grigolon, Giovanna, Mitchell, Sarah J., Zarse, Kim, Carreira, Erick M., Ristow, Michael
• Format: Article
• Language: English
• Subjects: 631/154/1435; 631/154/555; 631/443/7; 631/92/349/977; 64/11; 64/60; 692/699/317; Absolute configuration; Aging; Aging (natural); Animals; Asymmetric synthesis; ATP synthase; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Carrots; Daucus carota; Diet; Glucose; Glucose metabolism; High fat diet; Humanities and Social Sciences; Humans; Life span; Longevity; Mammalian cells; Mammals; Metabolism; Mice; Mice, Inbred C57BL; Mitochondria - metabolism; multidisciplinary; Neurodegeneration; Oxidative stress; Parameters; Polyacetylene; Polyynes - metabolism; Science; Science (multidisciplinary); Signatures; Stereoisomerism; Stereoisomers
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43672-7

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. Ameliorating or preventing signatures of aging in humans using natural compounds is an exciting area of research. Here the authors isolate a previously unknown phytochemical from carrots which activates defence mechanisms against oxidative stress and extends lifespan in worms, and improves glucose metabolism, promotes exercise capacity, and protects from frailty at higher age in mice.