Autor según el artículo: N Kolodkin A; Sharma RP; Colangelo AM; Ignatenko A; Martorana F; Jennen D; Briedé JJ; Brady N; Barberis M; Mondeel TDGA; Papa M; Kumar V; Peters B; Skupin A; Alberghina L; Balling R; Westerhoff HV

Departamento: Enginyeria Química

Autor/es de la URV: Kumar, Vikas

Resumen: © 2020, The Author(s). How the network around ROS protects against oxidative stress and Parkinson’s disease (PD), and how processes at the minutes timescale cause disease and aging after decades, remains enigmatic. Challenging whether the ROS network is as complex as it seems, we built a fairly comprehensive version thereof which we disentangled into a hierarchy of only five simpler subnetworks each delivering one type of robustness. The comprehensive dynamic model described in vitro data sets from two independent laboratories. Notwithstanding its five-fold robustness, it exhibited a relatively sudden breakdown, after some 80 years of virtually steady performance: it predicted aging. PD-related conditions such as lack of DJ-1 protein or increased α-synuclein accelerated the collapse, while antioxidants or caffeine retarded it. Introducing a new concept (aging-time-control coefficient), we found that as many as 25 out of 57 molecular processes controlled aging. We identified new targets for “life-extending interventions”: mitochondrial synthesis, KEAP1 degradation, and p62 metabolism.

Áreas temáticas: Modeling and simulation Mathematical & computational biology General biochemistry,genetics and molecular biology Drug discovery Computer science applications Biochemistry, genetics and molecular biology (miscellaneous) Biochemistry, genetics and molecular biology (all) Applied mathematics

Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/

Direcció de correo del autor: vikas.kumar@urv.cat

Identificador del autor: 0000-0002-9795-5967

Fecha de alta del registro: 2023-02-19

Volumen de revista: 6

Versión del articulo depositado: info:eu-repo/semantics/publishedVersion

Enlace a la fuente original: https://www.nature.com/articles/s41540-020-00150-w

URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/

Referencia al articulo segun fuente origial: Npj Syst Biol Appl. 6 (1): 34-

Referencia de l'ítem segons les normes APA: N Kolodkin A; Sharma RP; Colangelo AM; Ignatenko A; Martorana F; Jennen D; Briedé JJ; Brady N; Barberis M; Mondeel TDGA; Papa M; Kumar V; Peters B; Sk (2020). ROS networks: designs, aging, Parkinson’s disease and precision therapies. Npj Syst Biol Appl, 6(1), 34-. DOI: 10.1038/s41540-020-00150-w

DOI del artículo: 10.1038/s41540-020-00150-w

Entidad: Universitat Rovira i Virgili

Año de publicación de la revista: 2020

Tipo de publicación: Journal Publications