9. De la Déesse Clotho qui file la trame de vie à la découverte d’une protéine de jouvence

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Cette 9ème chronique démarre avec 3 déesses de la mythologie grecque appelées les Moires et qui déterminent la destinée des hommes. Parmi ces 3 divinités, Clotho est la Moire qui tisse le fil de la vie des hommes. Cette chronique se poursuit par une surprenante découverte faite par des chercheurs japonais qui identifient en 1997 un gène dont la destruction dans une cellule œuf de souris provoque une forme spectaculaire de vieillissement prématuré. Et ces chercheurs vont donner à ce gène le nom de klotho. Depuis la découverte du gène klotho, de nombreuses études vont permettre de préciser les effets et le mode d’action de la protéine codée par ce gène. Klotho s’avère être non seulement une protéine de longévité, mais elle peut aussi favoriser le fonctionnement cérébral, retarder le développement des symptômes de maladies neurodégénératives et permettre de lutter contre certains cancers.

Auteur : Yves Muller – Professeur Agrégé de classe exceptionnelle - Docteur en Neurosciences - Université de Montpellier

9. Biological Chronicles - From the Goddess Clotho who spins the web of life, to the discovery of a protein of youth.

Our chronicle begins with 3 goddesses from Greek mythology called the Moirai, the Fates, who decide the destiny of men. Among these 3 divinities, Clotho is the Fate who weaves the thread of life. This chronicle continues with a surprising discovery made by Japanese researchers in 1997 who identified a gene whose destruction in the cell of a mouse egg caused a spectacular form of premature ageing. They gave the gene the name of klotho. Since the discovery of the klotho gene, numerous studies have been able to specify the effects and the mode of action of the protein encoded by this gene. Klotho has been shown to be not only a longevity protein, but it can also promote brain function, delay the development of symptoms of neurodegenerative diseases and help fight certain cancers.

Author : Yves Muller – Associate Professor at Montpellier University

Références :

- Jean Claude Ameisen - La sculpture du vivant – Le suicide cellulaire ou la mort créatrice – Editions du Seuil, 1999.

- Leon J, Moreno AJ, Garay BI, et coll. Peripheral elevation of a Klotho fragment enhances brain function and resilience in young, aging, and α-synuclein transgenic mice. Cell Reports 2017 Aug. 8, 20:1360-1371.

- Dubal DB, Zhu L, Sanchez PE, et coll. Life extension factor klotho prevents mortality and enhances cognition in hAPP transgenic mice. The Journal of Neuroscience 2015, 35:2358-71.

- Dubal DB, Yokoyama JS, Zhu L, et coll. Life extension factor klotho enhances cognition. Cell Reports 2014, 7:1065-76.

- Zeldich E, Chen CD, Colvin TA, et coll. The neuroprotective effect of Klotho is mediated via regulation of members of the redox system. The Journal of Biological Chemistry 2014, 289:24700-15.

- Kurosu H, Yamamoto M, Clark JD, et coll. Suppression of aging in mice by the hormone Klotho. Science 2005, 309:1829-33.

- Nagai T, Yamada K, Kim HC, et coll. Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress. The FASEB Journal 2003, 17:50-2.

- Kuro-o M, Matsumura Y, Aizawa H, et coll. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997, 390:45-51.

- Ella Zeldich, Ci-Di Chen, Emma Boden, et coll. Klotho Is Neuroprotective in the Superoxide Dismutase (SOD1G93A) Mouse Model of ALS. J Mol Neurosci 2019; 69 (2): 264-285.

- Jean Claude Ameisen, Clotho et le fil de vie, émission sur France Inter, Sur les épaules de Darwin (2017).

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