The Trajectory of Successful Aging: Insights from Metagenome and Cytokine Profiling

Abstract

<b><i>Introduction:</i></b> The longevity is influenced by genetic, environmental, and lifestyle factors. The specific changes that occur in the gut microbiome during the aging process, and their relationship to longevity and immune function, have not yet been fully understood. The ongoing research of other microbiome based on longevity cohort in Kazakhstan provides preliminary information on longevity-related aging, where cytokine expression is associated with specific microbial communities and microbial functions. <b><i>Methods:</i></b> Metagenomic shotgun sequencing study of 40 long-lived individuals aged 90 years and over was carried out, who were conditionally healthy and active, able to serve themselves, without a history of serious infection and cancer, who had not taken any antimicrobials, including probiotics. Blood serum was analyzed for clinical and laboratory characteristics. The cytokine and chemokine profile in serum and stool samples was assessed using multiplex analysis. <b><i>Results:</i></b> We found a significant increase in the expression of pro-inflammatory cytokines IL-1a, IL-6, 12p70, IP-10, IFNα2, IL-15, TNFa, as well as chemokines MIP-1a/CCL3 and MIP-1b/CCL4, chemokine motif ligands MCP-3/CCL7 and MDC/CCL22(1c). Nonagenerians and centenarians demonstrated a greater diversity of core microbiota genera and showed an elevated prevalence of the genera <i>Bacteroides</i>, <i>Clostridium</i>, <i>Escherichia</i>, and <i>Alistipes</i>. Conversely, there was a decrease in the abundance of the genera <i>Ruminococcus</i>, <i>Fusicatenibacter</i>, <i>Dorea</i>, as well as the species <i>Fusicatenibacter saccharivorans</i>. Furthermore, functional analysis revealed that the microbiome in long-lived group has a high capacity for lipid metabolism, amino acid degradation, and potential signs of chronic inflammatory status. <b><i>Conclusion:</i></b> Long-lived individuals exhibit an immune system imbalance and observed changes in the composition of the gut microbiota at the genus level between to the two age-groups. Age-related changes in the gut microbiome, metabolic functions of the microbial community, and chronic inflammation all contribute to immunosenescence. In turn, the inflammatory state and microbial composition of the gut is related to nutritional status.