Аннотация
Старение организма протекает неравномерно, затрагивая различные органы и системы, включая ткани полости рта. Органоспецифическим компонентом полости рта является ротовая жидкость (РЖ), изменение состава которой может отражать процессы стоматологического старения. Цель работы – оценить возрастные изменения биохимических параметров
РЖ практически здоровых людей и выявить потенциальные саливарные биомаркеры старения. Проведено исследование 92
практически здоровых лиц четырёх возрастных групп: детского возраста от 7 до 12 лет (n=24), молодого — от 18 до 44 лет
(n=28), зрелого — от 45 до 59 лет (n=20), пожилого — от 60 до 74 лет (n=20). Для оценки физико-химических параметров
РЖ применяли диагностические тест-полоски Multistix 10 SG (Siemens, США), отражательный фотометр Clinitek Status+
(Siemens, США), химический анализатор Mindray BC-240pro (Mindray, КНР). В работе проводилось определение 16-ти биохимических параметров РЖ и 4-х, рассчитанных на их основе, индексов. Поскольку РЖ является нестандартизованной биожидкостью, непосредственно определяемые параметры пересчитывали путём деления на концентрацию общего белка пробы. Установлено, что исследованные группы пациентов различались по следующим, непосредственно определяемым параметрам: общий белок, альбумин, щелочная фосфатаза, неорганический фосфор, общий антиоксидантный статус, мочевая
кислота, холестерин, лактатдегидрогеназа, лактатдегидрогеназа-1, креатинин, мочевина, магний. После стандартизации
результатов по концентрации общего белка установлены различия по следующим показателям: холестерин, α-амилаза общая, С-реактивный белок, креатинин, магний. Оценивались корреляционные связи между стандартизованными параметрами и хронологическим возрастом. Установлено, что с хронологическим возрастом пациентов положительно коррелировал
общий белок, альбумин, холестерин, фосфорно-кальциевое соотношение, отрицательно — α-амилаза общая, С-реактивный
белок. Возрастные изменения большинства исследованных параметров могут объясняться возрастным морфофункциональным преобразованием тканей полости рта. Некоторые показатели, в частности, креатинин, могут изменяться под влиянием системных факторов.
Annotation
The aging of organism proceeds unevenly and affects various organs and systems, including oral cavity. Mixed saliva is a useful component that can reflect the aging processes of the oral cavity. The aim of the study was to evaluate age-related changes in the mixed
saliva biochemical markers of healthy people and to identify potential aging biomarkers. The study included 92 healthy people of four
age groups: children from 7 to 12 years old (n=24), young people from 18 to 44 (n=28), mature from 45 to 59 (n=20), elderly from 60
to 74 (n=20). Reagent strips Multistix 10SG (Siemens,USA), analyzer Clinitek Status+ (Siemens,USA), chemistry analyzer Mindray
BC-240pro (Mindray,China) were used to evaluate mixed saliva physico-chemical markers. In total, 16 biochemical markers and 4
calculated indices were determined in the study. Saliva results were expressed without any correction, and corrected by total protein
concentration. It was found that studied groups differed in the following markers without correction: total protein, albumin, alkaline
phosphatase, inorganic phosphorus, total antioxidant capacity, uric acid, cholesterol, lactated dehydrogenase, lactate dehydrogenase-1, creatinine, urea, magnesium. After correction by total protein concentration, differences were found in the following indicators:
cholesterol, total α-amylase, c-reactive protein, creatinine, magnesium. Correlations between corrected markers and chronological
age were evaluated. It was found that total protein, albumin, cholesterol, phosphorus-calcium ratio, creatinine positively correlated
with chronological age, and total α-amylase, c-reactive protein – negatively. The change of mixed saliva composition with age can be
explained by age-related oral tissues morphofunctional transformation. We combine creatinine age dynamics with system processes.
Key wоrds: aging;aging biomarkers; saliva; oral health
Список литературы
1. Sprott R.L. Biomarkers of aging and disease: introduction and definitions. Exp. Gerontol. 2010; 45(1): 2-4. DOI: 10.1016/j.exger.2009.07.008.
2. Aging Biomarker Consortium. Bao H., Cao J., Chen M., Chen M., Chen W. et al. Biomarkers of aging. Sci. China Life Sci. 2023; 66(5): 893-1066. DOI: 10.1007/s11427-023-2305-0.
3. Jakovljevic D.G. Physical activity and cardiovascular aging: Physiological and molecular insights. Exp. Gerontol. 2018; 109: 67-74. DOI:10.1016/j.exger.2017.05.016.
4. Denic A., Rule A.D., Glassock R.J. Healthy and unhealthy aging on kidney structure and function: human studies. Curr. Opin Nephrol. Hypertens. 2022; 31(3): 228-34. DOI: 10.1097/
MNH.0000000000000780.
5. Bartlett D., O’Toole S. Tooth wear and aging. Aust. Dent. J. 2019; Suppl.1: 59-62. DOI: 10.1111/adj.12681.
6. Lamster I.B., Asadourian L., Del Carmen T., Friedman P.K. The aging mouth: differentiating normal aging from disease. Periodontol. 2000. 2016; 72(1): 96-107. DOI: 10.1111/prd.12131.
7. Bazarnyi V.V. Salivary biomarkers of age-dependent processes (review). Laboratornaya sluzhba. 2022; 11(3): 28‑33. DOI: 10.17116/labs20221103128. (in Russian)
8. Thompson L.A., Chen H. Physiology of aging of older adults. Dental Clinics of North America. 2021; 65(2): 275-84. DOI: 10.1016/j.cden.2020.11.002.
9. Xu F., Laguna L., Sarkar A. Aging-related changes in quantity and quality of saliva: Where do we stand in our understanding? J. Texture Stud. 2019; 50(1): 27-35. DOI: 10.1111/jtxs.12356.
10. González‐Moles M.A., Warnakulasuriya S., Gonzalez‐Ruiz I., Gonzalez‐Ruiz L., Ayen A., Lenouvel D. et al. Worldwide prevalence of oral lichen planus: a systematic review and meta‐analysis. Oral Diseases. 2021; 27(4): 813-28. DOI:10.1111/odi.13323.
11. Maciejczyk M., Zalewska A., Ładny J.R. Salivary antioxidant barrier, redox status, and oxidative damage to proteins and lipids in healthy children, adults, and the elderly. Oxid. Med. Cell Longev. 2019; 2019: 4393460. DOI: 10.1155/2019/4393460.
12. Selezneva I.A., Gilmiyarova F.N., Tlustenko V.S., Domenjuk D.A., Gusyakova O.A., Kolotyeva N.A. et al. Hematosalivarian barrier: structure, functions, study methods (review of literature). Klinicheskaya Laboratornaya Diagnostika. 2022; 67(6): 334-8. DOI: 10.51620/0869-2084-2022-67-6-334-338. (in Russian)
13. Bel’skaya L.V., Sarf E.A., Kosenok V.K. Correlation interrelations between the composition of saliva and blood plasmain norm. Klinicheskaya Laboratornaya Diagnostika. 2018; 63(8): 477-82. DOI: 10.18821/0869-2084-2018-63-8-477-482. (in Russian)
14. Ghallab N.A. Diagnostic potential and future directions of biomarkers in gingival crevicular fluid and saliva of periodontal diseases: review of the current evidence. Archives of oral biology. 2018; 87: 115-24. DOI: 10.1016/j.archoralbio.2017.12.022.
15. Ide M., Karimova M., Setterfield J. Oral health, antimicrobials and care for patients with chronic oral diseases – a review of knowledge and treatment strategies. Front. Oral Health. 2022; 3: 866695. DOI: 10.3389/froh.2022.866695.
16. Engelfriet P.M., Jansen E.H., Picavet H.S., Dollé M.E. Biochemical markers of aging for longitudinal studies in humans. Epidemiol. Rev. 2013; 35(1): 132-51. DOI: 10.1093/epirev/mxs011.
17. Dodig S., Čepelak I., Pavić I. Hallmarks of senescence and aging. Biochem. Med. (Zagreb). 2019; 29(3): 030501. DOI: 10.11613/ BM.2019.030501.
18. Marcinkowska-Gapińska A., Siemieniak I., Kawałkiewicz W., Stieler O., Hojan-Jezierska D., Kubisz L. Interdependence of rheological and biochemical parameters of blood in a group of patients with clinically silent multifocal vascular cerebral lesions. Biomedicines. 2023; 11(7): 2063. DOI: 10.3390/biomedicines11072063.
19. González-Hernández J.M., Franco L., Colomer-Poveda D., Martinez-Subiela S., Cugat R., Cerón J.J. et al. Influence of sampling conditions, salivary flow, and total protein content in uric acid measurements in saliva. Antioxidants (Basel). 2019; 8(9): 389. DOI: 10.3390/
antiox8090389.
20. Kang J.H., Kho H.S. Blood contamination in salivary diagnostics: current methods and their limitations. Clin. Chem. Lab. Med. 2019; 57(8): 1115-24. DOI: 10.1515/cclm-2018-0739.
21. Dawes C., Wong D.T.W. Role of saliva and salivary diagnostics in the advancement of oral health. J. Dent. Res. 2019; 98(2): 133-41. DOI: 10.1177/0022034518816961.
22. Kejriwal S., Bhandary R., Thomas B., Kumari S. Estimation of levels of salivary mucin, amylase and total protein in gingivitis and chronic periodontitis patients. J. Clin. Diagn. Res. 2014; 8(10): 56-60. DOI:10.7860/JCDR/2014/8239.5042.
23. Karjalainen S., Sewón L., Söderling E., Larsson B., Johansson I., Simell O. et al. Salivary cholesterol of healthy adults in relation to
serum cholesterol concentration and oral health. J. Dent. Res. 1997; 76(10): 1637-43. DOI: 10.1177/00220345970760100401.
24. Kensche A., Reich M., Kümmerer K., Hannig M., Hannig C. Lipids in preventive dentistry. Clin. Oral Investig. 2013; 17(3): 669-85. DOI:10.1007/s00784-012-0835-9.
25. Tvarijonaviciute A., Aznar-Cayuela C., Rubio C.P., Ceron J.J., LópezJornet P. Evaluation of salivary oxidate stress biomarkers, nitric oxide and C-reactive protein in patients with oral lichen planus and burning mouth syndrome. Journal of Oral Pathology and Medicine. 2016; 46(5): 387-92. DOI: 10.1111/jop.12522.
26. Ersin Kalkan R., Öngöz Dede F., Gökmenoğlu C., Kara C. Salivary fetuin-A, S100A12, and high-sensitivity C-reactive protein levels in periodontal diseases. Oral Dis. 2018; 24(8): 1554-61. DOI: 10.1111/odi.12927.
27. Plank A.C., Maschke J., Rohleder N., Fasching P.A., Beckmann M.W., Kornhuber J. et al. Comparison of С-reactive protein in dried blood spots and saliva of healthy adolescents. Front. Immunol. 2021;
12: 795580. DOI: 10.3389/fimmu.2021.795580. 28. Clark D., Radaic A., Kapila Y. Cellular mechanisms of inflammaging and periodontal disease. Front Dent. Med. 2022; 3: 844865. DOI:
10.3389/fdmed.2022.844865.
29. Jazaeri M., Malekzadeh H., Abdolsamadi H., Rezaei-Soufi L., Samami M. Relationship between salivary alkaline phosphatase enzyme activity and the concentrations of salivary calcium and phosphate ions. Cell J. 2015; 17(1): 159-62. DOI: 10.22074/cellj.2015.523.
30. Tsepov L.M., Tsepova E.L., Tsepov A.L. Comorbidity: inflammatory periodontal diseases, osteoporosis, vitamin D deficiency (review of the literature). Parodontologiya. 2016; 21(4): 4-9. (in Russian)
31. Nassar M., Hiraishi N., Islam S., Otsuki M., Tagami J. Age-related changes in salivary biomarkers. Journal of Dental Sciences. 2014, 9(1): 85-90. DOI: 10.1016/j.jds.2013.11.002.
32. Nagler R.M., Hershkovich O. Relationships between age, drugs, oral sensorial complaints and salivary profile. Archives of Oral Biology. 2005; 50(1): 7-16. DOI: 10.1016/j.archoralbio.2004.07.
33. Bilancio G., Cavallo P., Lombardi C., Guarino E., Cozza V., Giordano F. et al. Saliva for assessing creatinine, uric acid, and potassium in nephropathic patients. BMC Nephrol. 2019; 20(1): 242. DOI: 10.1186/s12882-019-1437-4.
34. Yajamanam N., Vinapamula K.S., Sivakumar V., Bitla A.R., Rao P.V. Utility of saliva as a sample to assess renal function and estimated glomerular filtration rate. Saudi J. Kidney Dis. Transpl. 2016; 27(2): 312-9. DOI:10.4103/1319-2442.178549.
35. Gaál Kovalčíková A., Pančíková A., Konečná B., Klamárová T., Novák B., Kovaľová E. et al. Urea and creatinine levels in saliva of patients with and without periodontitis. Eur. J. Oral Sci. 2019; 127(5): 417-24. DOI: 10.1111/eos.12642.
36. Hartmann A., Hartmann C., Secci R., Hermann A., Fuellen G., Walter M. Ranking biomarkers of aging by citation profiling and effort scoring. Front Genet. 2021; 12: 686320. DOI: 10.3389/fgene.2021.686320.
37. Boeniger M.F., Lowry L.K., Rosenberg J. Interpretation of urine results used to assess chemical exposure with emphasis on creatinine adjustments: a review. American Industrial Hygiene Association Journal. 1993; 54(10): 615–27. DOI: 10.1080/15298669391355134.
38. Walsh N.P., Montague J.C., Callow N., Rowlands A.V. Saliva flow rate, total protein concentration and osmolality as potential markers of whole body hydration status during progressive acute dehydration in humans. Arch. Oral. Biol. 2004; 49(2): 149-54. DOI: 10.1016/j. archoralbio.2003.08.001.
39. Martínez-Subiela S., Franco-Martínez L., Rubio C.P., Muñoz-Prieto A., Torres-Cantero A., Tecles F. et al. Measurement of anti SARSCoV-2 RBD IgG in saliva: validation of a highly sensitive assay andeffects of the sampling collection method and correction by protein. Clin. Chem. Lab. Med. 2022; 60(10): 1683-9. DOI: 10.1515/cclm-2022-0418.