{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T10:36:15Z","timestamp":1769250975473,"version":"3.49.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T00:00:00Z","timestamp":1672358400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bulgarian National Science Fund","award":["K\u041f-06-H31\/8"],"award-info":[{"award-number":["K\u041f-06-H31\/8"]}]},{"name":"Italian CNR","award":["K\u041f-06-H31\/8"],"award-info":[{"award-number":["K\u041f-06-H31\/8"]}]},{"name":"Bulgarian Academy of Sciences","award":["K\u041f-06-H31\/8"],"award-info":[{"award-number":["K\u041f-06-H31\/8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Favism uniquely arises from a genetic defect of the Glucose-6 Phosphate Dehydrogenase (G6PD) enzyme and results in a severe reduction of erythrocytes\u2019 (RBCs) reducing power that impairs the cells\u2019 ability to respond to oxidative stresses. After exposure to fava beans or a few other drugs, the patients experience acute hemolytic anemia due to RBCs\u2019 lysis both intra and extra-vascularly. In the present paper, we compared selected biochemical, biophysical, and ultra-morphological properties of normal RBCs and cells from favism patients measured along cellular aging. Along the aging path, the cells\u2019 characteristics change, and their structural and functional properties degrade for both samples, but with different patterns and effectors that have been characterized in biophysical and biochemical terms. In particular, the analysis revealed distinct metabolic regulation in G6DP-deficient cells that determines important peculiarities in the cell properties during aging. Remarkably, the initial higher fragility and occurrence of structural\/morphological alterations of favism cells develop, with longer aging times, into a stronger resistance to external stresses and higher general resilience. This surprisingly higher endurance against cell aging has been related to a special mechanism of metabolic regulation that permits lower energy consumption in environmental stress conditions. Our results provided a direct and coherent link between the RBCs\u2019 metabolic regulation and the cell properties that would not have been possible to establish without an investigation performed during aging. The consequences of this new knowledge, in particular, can be discussed in a more general context, such as understanding the role of the present findings in determining the characteristics of the favism pathology as a whole.<\/jats:p>","DOI":"10.3390\/ijms24010637","type":"journal-article","created":{"date-parts":[[2022,12,30]],"date-time":"2022-12-30T03:31:17Z","timestamp":1672371077000},"page":"637","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Surprising Structural and Functional Properties of Favism Erythrocytes Are Linked to Special Metabolic Regulation: A Cell Aging Study"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9172-4973","authenticated-orcid":false,"given":"Simone","family":"Dinarelli","sequence":"first","affiliation":[{"name":"Italian National Research Council (CNR), Institute for the Structure of the Matter (ISM), Via fosso del Cavaliere 100, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-2155","authenticated-orcid":false,"given":"Giovanni","family":"Longo","sequence":"additional","affiliation":[{"name":"Italian National Research Council (CNR), Institute for the Structure of the Matter (ISM), Via fosso del Cavaliere 100, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefka","family":"Germanova-Taneva","sequence":"additional","affiliation":[{"name":"Bulgarian Academy of Sciences (BAS), Institute of Biophysics and Biomedical Engineering, G. Bonchev Str. 21, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7108-051X","authenticated-orcid":false,"given":"Svetla","family":"Todinova","sequence":"additional","affiliation":[{"name":"Bulgarian Academy of Sciences (BAS), Institute of Biophysics and Biomedical Engineering, G. Bonchev Str. 21, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7412-8398","authenticated-orcid":false,"given":"Sashka","family":"Krumova","sequence":"additional","affiliation":[{"name":"Bulgarian Academy of Sciences (BAS), Institute of Biophysics and Biomedical Engineering, G. Bonchev Str. 21, 1113 Sofia, Bulgaria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6146-2979","authenticated-orcid":false,"given":"Marco","family":"Girasole","sequence":"additional","affiliation":[{"name":"Italian National Research Council (CNR), Institute for the Structure of the Matter (ISM), Via fosso del Cavaliere 100, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.bcmd.2008.12.005","article-title":"The global prevalence of glucose-6- phosphate dehydrogenase deficiency: A systematic review and meta-analysis","volume":"42","author":"Nkhoma","year":"2009","journal-title":"Blood Cells Mol. 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