Abstract
This study aimed to examine the biological effects of blood plasma exchange in liver tissues of aged and young rats using machine learning methods and spectrochemical and histopathological approaches. Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) were the machine learning algorithms employed. Young plasma was given to old male rats (24 months), while old plasma was given to young male rats (5 weeks) for thirty days. LDA (95.83–100%) and SVM (87.5–91.67%) detected significant qualitative changes in liver biomolecules. In old rats, young plasma infusion increased the length of fatty acids, triglyceride, lipid carbonyl, and glycogen levels. Nucleic acid concentration, phosphorylation, and carbonylation rates of proteins were also increased, whereas a decrease in protein concentration was measured. Aged plasma decreased protein carbonylation, triglyceride, and lipid carbonyl levels. Young plasma infusion improved hepatic fibrosis and cellular degeneration and reduced hepatic microvesicular steatosis in aged rats. Otherwise, old plasma infusion in young rats caused disrupted cellular organization, steatosis, and increased fibrosis. Young plasma administration increased liver glycogen accumulation and serum albumin levels. Aged plasma infusion raised serum ALT levels while diminished ALP concentrations in young rats, suggesting possible liver dysfunction. Young plasma increased serum albumin levels in old rats. The study concluded that young plasma infusion might be associated with declined liver damage and fibrosis in aged rats, while aged plasma infusion negatively impacted liver health in young rats. These results imply that young blood plasma holds potential as a rejuvenation therapy for liver health and function.
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All data generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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There is not any custom computer code or algorithm used to generate the results reported in the manuscript.
References
Aksoy C, Severcan F (2012) Role of vibrational spectroscopy in stem cell research. Spectroscopy 27:167–184. https://doi.org/10.1155/2012/513286
Aksoy C, Severcan F (2019) Infrared spectroscopy and imaging in stem cells and aging research. Methods Mol Biol 2045:201–215. https://doi.org/10.1007/7651_2018_119
Andziak B, O’Connor TP, Qi W et al (2006) High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell 5:463–471. https://doi.org/10.1111/j.1474-9726.2006.00237.x
Ardahanlı İ, Özkan Hİ, Özel F et al (2022) Infrared spectrochemical findings on intermittent fasting-associated gross molecular modifications in rat myocardium. Biophys Chem 289:106873. https://doi.org/10.1016/j.bpc.2022.106873
Baker MJ, Trevisan J, Bassan P et al (2014) Using fourier transform IR spectroscopy to analyze biological materials. Nat Protoc 9:1771–1791. https://doi.org/10.1038/nprot.2014.110
Ballweg S, Sezgin E, Doktorova M et al (2020) Regulation of lipid saturation without sensing membrane fluidity. Nat Commun 11:756. https://doi.org/10.1038/s41467-020-14528-1
Bompard J, Rosso A, Brizuela L et al (2020) Membrane fluidity as a new means to selectively target cancer cells with fusogenic lipid carriers. Langmuir 36:5134–5144. https://doi.org/10.1021/acs.langmuir.0c00262
Castellano JM (2019) Blood-based therapies to combat aging. Gerontology 65:84–89. https://doi.org/10.1159/000492573
Ceylani T, Teker HT (2022) The effect of young blood plasma administration on gut microbiota in middle-aged rats. Arch Microbiol 204:541. https://doi.org/10.1007/s00203-022-03154-8
Ceylani T, Taner H, Samgane G, Gurbanov R (2022) Intermittent fasting-induced biomolecular modifications in rat tissues detected by ATR-FTIR spectroscopy and machine learning algorithms. Anal Biochem 654:114825. https://doi.org/10.1016/j.ab.2022.114825
Ceylani T, Allahverdi H, Teker HT (2023) Role of age-related plasma in the diversity of gut bacteria. Arch Gerontol Geriatr 111:105003. https://doi.org/10.1016/j.archger.2023.105003
Cloos PAC, Christgau S (2004) Post-translational modifications of proteins: implications for aging, antigen recognition, and autoimmunity. Biogerontology 5:139–158. https://doi.org/10.1023/B:BGEN.0000031152.31352.8b
Dicko A, Bourque H, Pézolet M (1998) Study by infrared spectroscopy of the conformation of dipalmitoylphosphatidylglycerol monolayers at the air-water interface and transferred on solid substrates. Chem Phys Lipids 96:125–139. https://doi.org/10.1016/S0009-3084(98)00084-X
Doble BW, Woodgett JR (2003) GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci 116:1175–1186. https://doi.org/10.1242/jcs.00384
Dogan A, Gurbanov R, Severcan M, Severcan F (2021) CoronaVac (Sinovac) COVID-19 vaccine-induced molecular changes in healthy human serum by infrared spectroscopy coupled with chemometrics. Turk J Biol 45:549–558. https://doi.org/10.3906/biy-2105-65
Dreier LB, Bonn M, Backus EHG (2019) Hydration and orientation of carbonyl groups in oppositely charged lipid monolayers on water. J Phys Chem B 123:1085–1089. https://doi.org/10.1021/acs.jpcb.8b12297
Erdogan K, Ceylani T, Teker HT et al (2023) Young plasma transfer recovers decreased sperm counts and restores epigenetics in aged testis. Exp Gerontol 172:112042. https://doi.org/10.1016/j.exger.2022.112042
Finch CE, Crimmins EM (2016) Constant molecular aging rates vs. the exponential acceleration of mortality. Proc Natl Acad Sci USA 113:1121–1123
Goh GB-B, Pagadala MR, Dasarathy J et al (2015) Age impacts ability of aspartate-alanine aminotransferase ratio to predict advanced fibrosis in nonalcoholic fatty liver disease. Dig Dis Sci 60:1825–1831. https://doi.org/10.1007/s10620-015-3529-8
Gong Y, Fan Z, Luo G et al (2019) The role of necroptosis in cancer biology and therapy. Mol Cancer 18:100. https://doi.org/10.1186/s12943-019-1029-8
Gurbanov R, Yıldız F (2017) Molecular profile of oral probiotic bacteria to be used with functional foods. J Food Health Sci 12:117–131. https://doi.org/10.3153/jfhs17015
Gurbanov R, Karadağ H, Karaçam S, Samgane G (2021) Tapioca starch modulates cellular events in oral probiotic streptococcus salivarius strains. Probiotics Antimicrob Proteins 13:195–207. https://doi.org/10.1007/s12602-020-09678-z
Heydari AR, Butler JA, Waggoner SM, Richardson A (1989) Age-related changes in protein phosphorylation by rat hepatocytes. Mech Ageing Dev 50:227–248. https://doi.org/10.1016/0047-6374(89)90102-4
Huang Q, Ning Y, Liu D et al (2018) A Young blood environment decreases aging of senile mice kidneys. J Gerontol A Biol Sci Med Sci 73:421–428. https://doi.org/10.1093/gerona/glx183
Jin J, Wang G-L, Shi X et al (2009) The age-associated decline of glycogen synthase kinase 3beta plays a critical role in the inhibition of liver regeneration. Mol Cell Biol 29:3867–3880. https://doi.org/10.1128/MCB.00456-09
Kazarian SG, Chan KLA (2006) Applications of ATR-FTIR spectroscopic imaging to biomedical samples. Biochimica et Biophysica Acta (BBA)—Biomembr. https://doi.org/10.1016/j.bbamem.2006.02.011
Kennedy BK, Berger SL, Brunet A et al (2014) Geroscience: linking aging to chronic disease. Cell 159:709–713
Keskin S, Acikgoz E, Ertürk FY, Ragbetli MC (2022) Histopathological changes in liver and heart tissue associated with experimental ultraviolet radiation a and b exposure on wistar albino rats. Photochem Photobiol. https://doi.org/10.1111/php.13664
Krisko A, Radman M (2019) Protein damage, ageing and age-related diseases. Open Biol. https://doi.org/10.1098/rsob.180249
Liu A, Guo E, Yang J et al (2018) Young plasma reverses age-dependent alterations in hepatic function through the restoration of autophagy. Aging Cell. https://doi.org/10.1111/acel.12708
Liu J-F, Wu Y, Yang Y-H et al (2022) Phosphoproteome profiling of mouse liver during normal aging. Proteome Sci 20:12. https://doi.org/10.1186/s12953-022-00194-2
Loffredo FS, Steinhauser ML, Jay SM et al (2013) Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell 153:828–839. https://doi.org/10.1016/j.cell.2013.04.015
Mohamad M, Mitchell SJ, Wu LE et al (2016) Ultrastructure of the liver microcirculation influences hepatic and systemic insulin activity and provides a mechanism for age-related insulin resistance. Aging Cell 15:706–715. https://doi.org/10.1111/acel.12481
Morsiani C, Bacalini MG, Santoro A et al (2019) The peculiar aging of human liver: a geroscience perspective within transplant context. Ageing Res Rev 51:24–34. https://doi.org/10.1016/j.arr.2019.02.002
Ohto T, Backus EHG, Hsieh C-S et al (2015) Lipid carbonyl groups terminate the hydrogen bond network of membrane-bound water. J Phys Chem Lett 6:4499–4503. https://doi.org/10.1021/acs.jpclett.5b02141
Paraboni MLR, Kalinoski J, Braciak BG et al (2022) Protein carbonyl products, malondialdehyde, glutathione and vitamins C/E of breast cancer patients subjected to chemotherapy. Braz J Oncol 18:1–8. https://doi.org/10.5935/2526-8732.20220302
Severcan F, Haris PI (2012) Vibrational spectroscopy in diagnosis and screening. IOS Press, Amsterdam
Singh P, Goode T, Dean A et al (2011) Elevated interferon gamma signaling contributes to impaired regeneration in the aged liver. J Gerontol A Biol Sci Med Sci 66:944–956. https://doi.org/10.1093/gerona/glr094
Ticinesi A, Nouvenne A, Cerundolo N et al (2019) Gut microbiota, muscle mass and function in aging: a focus on physical frailty and sarcopenia. Nutrients. https://doi.org/10.3390/nu11071633
Timchenko NA (2009) Aging and liver regeneration. Trends Endocrinol Metab 20:171–176. https://doi.org/10.1016/j.tem.2009.01.005
Tripathi SS, Kumar R, Arya JK, Rizvi SI (2021) Plasma from young rats injected into old rats induce anti-aging effects. Rejuvenation Res 24:206–212. https://doi.org/10.1089/rej.2020.2354
Villeda SA, Plambeck KE, Middeldorp J et al (2014) Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Nat Med 20:659–663. https://doi.org/10.1038/nm.3569
Wang L, Li J, Dijun L (2022) Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases. Med Res Rev 42:946–982
Acknowledgements
The authors are grateful to the Department of Chemistry at Bilecik Şeyh Edebali University for providing an FTIR spectrometer and to Adem Kurtcuoğlu for his contributions.
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HTT: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Software, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. TC: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Resources, Software, Supervision, Validation, Visualization, Writing—original draft, Writing—review & editing. SK: Histopathological analysis, Biochemical and Histopathological interpretation, Visualization, Writing–original draft, Writing—review & editing. GS: Investigation, Methodology, Resources, Software, Supervision, Validation, Visualization. SM: Investigation, Methodology, Resources, Software, Supervision, Validation, Visualization. BB: Resources, Funding acquisition, Supervision, Visualization. HA: Resources, Funding acquisition, Supervision, Visualization. EA: Histopathological and Biochemical interpretation, Visualization, Writing—original draft, Writing—review & editing. Rafig Gurbanov: Investigation, Methodology, Resources, Software, Supervision, Validation, Writing—review & editing, Visualization.
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Teker, H.T., Ceylani, T., Keskin, S. et al. Age-related differences in response to plasma exchange in male rat liver tissues: insights from histopathological and machine-learning assisted spectrochemical analyses. Biogerontology 24, 563–580 (2023). https://doi.org/10.1007/s10522-023-10032-3
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DOI: https://doi.org/10.1007/s10522-023-10032-3