Features of the expression of genes of antimicrobial peptides and the microbiome at the level of the mucous membrane of the upper respiratory tract during aging

Today, the proportion of elderly and senile people is steadily growing throughout the world. The most important factors in the first line of immune defense of the mucous membranes of the upper respiratory tract are β-defensins, which are a group of secretory proteins with antimicrobial activity. The aim of this study was to study the expression of genes for antimicrobial peptides β-defensins and the composition of the microbiome of the mucous membranes of the upper respiratory tract in elderly people and long-livers with various aging phenotypes.

The main study group included 67 centenarians and 49 elderly people, who were further divided into two subgroups depending on the course of aging (pathological and successful aging). Nucleic acids were isolated from nasopharyngeal scrapings and the expression levels of the DEFB1 and DEFB4 genes were determined using real-time polymerase chain reaction. The composition of the microbiota in nasopharyngeal swabs was determined by MALDI-TOF mass spectrometry.

In analyzing the expression of the DEFB1 gene in elderly people and centenarians with successful and pathological aging phenotypes, no difference was revealed between the groups. Expression of the DEFB4 gene was increased in centenarians with pathological aging compared to centenarians with successful aging and in the elderly group. Excessive production of antimicrobial peptides is dual in nature; on the one hand, they provide the first line of defense against microorganisms, and on the other, they are cytotoxic to their own cells. An increase in the expression of the DEFB4 gene during aging may be due to an increase in the number of pathogen-associated molecular patterns, which can be one’s own microbiota and/or components of microbial metabolism. Analysis of the microbiota composition showed an increase in biodiversity in individuals with a successful aging phenotype compared to a pathological phenotype. Particular attention is paid to Staphylococcus spp., the species composition of which depends on the aging phenotype. In the pathological aging group, the frequency of St. aureus colonization is significantly higher than in the successful aging group.

Thus, overexpression of the DEFB4 gene and changes in the composition of the microbiota of the mucous membranes of the upper respiratory tract may be one of the mechanisms explaining the increased susceptibility to infections in various aging phenotypes.

1. Rebrikov D.V., Trofimov D.Yu. Real-time PCR: a review of approaches to data analysis. Prikladnaya biokhimiya i mikrobiologiya = Applied Biochemistry and Microbiology, 2006, Vol. 42, no. 5, pp. 455-463. (In Russ.)

2. Shamova O.V., Zharkova M.S., Chernov A.N., Vladimirova E.V., Sukhareva M.S., Komlev A.S., Kochenda O.L., Orlov D.S. Antimicrobial peptides of innate immunity as prototypes of new agents to fight antibiotic-resistant bacteria. Rossiyskiy zhurnal personalizirovannoy meditsiny = Russian Journal for Personalized Medicine, 2021, Vol. 1, no. 1, pp. 146-172. (In Russ.)

3. Alan P. Baptist, Sharmilee Nyenhuis. Rhinitis in the elderly. Immunol. Allergy Clin. North Am., 2016, Vol. 36, no. 2, pp. 343-357.

4. Arevalo-Rodriguez I., Smailagic N., Roqué-Figuls M., Ciapponi A., Sanchez-Perez E., Giannakou A., Pedraza O.L., Cosp X.B., Cullum S. Mini-Mental State Examination (MMSE) for the early detection of dementia in people with mild cognitive impairment (MCI). Cochrane Database Syst Rev., 2021, Vol. 7, no. 7, pp. 345-367.

5. Bright J., Claydon M., Soufian M., Gordon D. Rapid typing of bacteria using matrix-assisted laser desorption ionisation time-of-flight mass spectrometry and pattern recognition software. J. Microbiol. Methods, 2002, Vol. 48, no. 2-3, pp. 127-138.

6. Castañeda-Delgado J.E., Frausto-Lujan I., González-Curiel I., Montoya-Rosales A., Serrano C.J., Torres-Juarez F., Enciso-Moreno J.A., Rivas-Santiago B. Differences in cytokine production during aging and its relationship with antimicrobial peptides production. Immunol. Investig., 2017, Vol. 46, no. 1, pp. 48-58.

7. Charlson M., Carrozzino D., Guidi J., Chiara Patierno C. Charlson comorbidity index: a critical review of clinimetric properties. Psychother. Psychosom., 2022, Vol. 91, no. 1, pp. 8-35.

8. Hertz C.J., Wu Q., Porter E.M., Zhang Y.J., Weismüller K., Godowski P.J., Ganz T., Randell S.H., Modlin R.L. Activation of Toll-like receptor 2 on human tracheobronchial epithelial cells induces the antimicrobial peptide human β defensin-2. J. Immunol., 2003, Vol. 171, no. 12, pp. 6820-6826.

9. Ji S., Shin J.E., Kim Y.S., Oh J.E., Min B.M., Choi Y. Toll-like receptor 2 and NALP2 mediate induction of human beta-defensins by fusobacterium nucleatum in gingival epithelial cells. Infect. Immun., 2009, Vol. 77, no. 3, pp. 1044-1052.

10. Kohtaro F., Hiroshi K. Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol., 2009, Vol. 30, no. 7, pp. 334-343.

11. Kumar A., Zhang J., Yu F.S. Toll-like receptor 2-mediated expression of beta-defensin-2 in human corneal epithelial cells. Microbes Infect., 2006, Vol. 8, no. 2, pp. 380-389.

12. Ramírez-Vélez R., de Asteasu M.L.S., Morley J., Cano-Gutierrez C., Izquierdo M. Performance of the short physical performance battery in identifying the frailty phenotype and predicting geriatric syndromes in community-dwelling elderly. J. Nutr. Health Aging, 2020, Vol. 25, no. 2, pp. 209-217.

13. Takiishi T., Fenero C.I.M., Câmara N.O.S. Intestinal barrier and gut microbiota: Shaping our immune responses throughout life. Tissue Barriers, 2017, Vol. 5, no. 4, pp. 234-245.