Author, as appears in the article.: 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

Department: Enginyeria Química

URV's Author/s: Kumar, Vikas

Abstract: © 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.

Thematic Areas: 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

licence for use: https://creativecommons.org/licenses/by/3.0/es/

Author's mail: vikas.kumar@urv.cat

Author identifier: 0000-0002-9795-5967

Record's date: 2023-02-19

Journal volume: 6

Papper version: info:eu-repo/semantics/publishedVersion

Link to the original source: https://www.nature.com/articles/s41540-020-00150-w

Licence document URL: http://repositori.urv.cat/ca/proteccio-de-dades/

Papper original source: Npj Syst Biol Appl. 6 (1): 34-

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

Article's DOI: 10.1038/s41540-020-00150-w

Entity: Universitat Rovira i Virgili

Journal publication year: 2020

Publication Type: Journal Publications