A new biochemical principle involving the interplay between oxidative stress and phosphorylation uncovered in aging

Ageing plays a crucial role in the development of several important human diseases, including cardiovascular, cancer, and neurodegenerative diseases. Understanding the ageing process is key to the early diagnosis and treatment of these diseases. A new research led from Lleida (Spain) has uncovered a new biochemical principle that interferes with ageing-related pathology-a promising finding for future clinical applications.

"Until now we knew that at the molecular level, ageing affects protein regulation and leads to degenerative modifications on certain proteins, such as aberrant serine phosphorylation (p-Ser), which is a direct cause of toxic protein accumulation within the brain in Alzheimer's disease; and trioxidized cysteine (t-Cysteine), which is a product of increased oxidative stress, but an underlying molecular mechanism linking these two factors in ageing diseases was unknown," explained Xavier Gallart, professor at the University of Lleida and researcher at the Institute for Research in Biomedicine of Lleida (IRBLleida). "This study establishes, for the first time, a connection at the molecular level between oxidative stress and aberrant phosphorylation of proteins in the proteome, two fundamental mechanisms that interfere, and now we know better how, in pathologies in which ageing is a key factor," said Aida Serra, professor at the University of Lleida and researcher at IRBLleida.

The research, led by the leaders of the +Pec Proteomics research group, Xavier Gallart-Palau and Aida Serra, in collaboration with Professor Newman Sze of Brock University in Canada, has been published in the journal Aging Cell. This two-year study analyzed the proteome of aging mice using advanced proteomics techniques-a branch of systems biology that globally analyzes all the proteins of a cell, tissue, or organism in specific and defined conditions-and bioinformatics.

"The research opens up new avenues of investigation into the role of these protein modifications in various chronic human diseases associated with aging," explained the first author of the article, José Antonio Sánchez Milán, PhD student of the research group +Pec Proteomics. "Similarly, it provides a new biochemical marker with potential clinical applications for assessing the risk of developing certain diseases associated with aging," added Newman Sze.

Funding Information

Instituto de Salud Carlos III, Grant/Award Number: PI22/00443 and CP21/00096; Agencia Estatal de Investigación, Grant/Award Number: PID2020-114885RB-C21, PR2021-097934 and RYC2021-030946-I; Ministerio de Ciencia, Innovación y Universidades (Spain) - Generalitat de Catalunya (Catalonia, Spain) - European Comission NextGeneration EU - Institute for Bioengineering of Catalonia (IBEC), Grant/Award Number: EVBRAINTARGET- Y7340-ACPPCCOL007 and PRTR-C17.I1; Diputació de Lleida, Grant/Award Number: PIRS22/03 and PIRS23/02; Agència de Gestió d'Ajuts Universitaris i de Recerca, Grant/Award Number: 2023 FI- 1 00054; Basque Government - IKUR Neurobiosciences and CERCA Program Generalitat de Catalunya; Canadian Institutes of Health Research, Grant/Award Number: CRC-2020- 00263 and PJT- 186091; Ontario Research Fund and Start- up grant from Brock University; Research Council of Canada and Canada Foundation for Innovation, Grant/Award Number: RGPIN-2023- 04304, 41454 and 44115; Singapore National Medical Research Council, Grant/Award Number: NMRC/OFIRG/0003/2016

Article: Sánchez Milán JA, Fernández-Rhodes M, Guo X, Mulet M, Ngan SC, Iyappan R, Katoueezadeh M, Sze SK, Serra A, Gallart-Palau X. Trioxidized cysteine in the aging proteome mimics the structural dynamics and interactome of phosphorylated serine. Aging Cell. 2023 Dec 18:e14062. doi: 10.1111/acel.14062. Epub ahead of print. PMID: 38111315.