Chronic inflammation is increasingly considered as the most important component of vascular aging, contributing to the progression of age‐related cardiovascular diseases. To delay the process of vascular aging, anti‐inflammation may be an effective measure. The anti‐inflammatory factor annexin A1 (ANXA1) is shown to participate in several age‐related diseases; however, its function during vascular aging remains unclear. Here, an ANXA1 knockout (ANXA1 ^−/− ) and an endothelial cell‐specific ANXA1 deletion mouse (ANXA1 ^△EC ) model are used to investigate the role of ANXA1 in vascular aging. ANXA1 depletion exacerbates vascular remodeling and dysfunction while upregulates age‐ and inflammation‐related protein expression. Conversely, Ac2‐26 (a mimetic peptide of ANXA1) supplementation reverses this phenomenon. Furthermore, long‐term tumor necrosis factor‐alpha (TNF‐α) induction of human umbilical vein endothelial cells (HUVECs) increases cell senescence. Finally, the senescence‐associated secretory phenotype and senescence‐related protein expression, rates of senescence‐β‐galactosidase positivity, cell cycle arrest, cell migration, and tube formation ability are observed in both ANXA1‐knockdown HUVECs and overexpressed ANXA1‐TNF‐α induced senescent HUVECs. They also explore the impact of formyl peptide receptor 2 (a receptor of ANXA1) in an ANXA1 overexpression inflammatory model. These data provide compelling evidence that age‐related inflammation in arteries contributes to senescent endothelial cells that promote vascular aging.

Elderly patients with sepsis have higher morbidity, mortality, and susceptibility than adults. Young-donor faecal microbiota transplantation (FMT) can remodel and improve intestinal dysbiosis to alleviate age-related diseases via microbiota-derived acetic acid and may be a treatment option for elderly sepsis. This study aimed to elucidate the influence of remodelling of the elderly gut microbiota on sepsis via acetic acid and explore the underlying mechanism. We analyzed the gut microbiota and plasma acetic acid in elderly patients with sepsis, performed young-donor FMT, and acetic acid supplementation in a caecum ligation and puncture-induced aged septic model mice, and assessed the effects of acetic acid on the septic myocardium by examining NLRP3 inflammasome in FFAR2 knockdown mice. Elderly sepsis had higher mortality, reduced gut microbiota diversity, increased Escherichia-Shigella abundance, and reduced plasma acetic acid levels. Young-donor FMT improved the gut microbiota, increased the abundance of the probiotic genus Akkermansia and faecal acetic acid levels in the gut, and improved colon barrier function and outcomes. Intestinal acetic acid intervention improved age-related intestinal dysbiosis, organ dysfunction, and adverse effects in aged septic mice. These beneficial effects on the myocardium were mediated by activation of the FFAR2/NLRP3 axis, as evidenced by the finding that FFAR2 knockdown abrogated the amelioration of acetic acid. The elderly gut microbiota is fragile, which is related to the severity and poor prognosis of elderly sepsis. Gut microbiota remodelling improves elderly sepsis via acetic acid, which can inhibit inflammatory reactions to alleviate myocardial damage by FFAR2/NLRP3 inflammasome inactivation.

The gut microbiota plays a crucial role in maintaining host health, and its composition is significantly influenced by aging. The SAMP8 mouse model, known for its accelerated aging process, is widely used to study age-related changes. However, comprehensive longitudinal studies on gut microbiota dynamics in SAMP8 mice remain limited. We analyzed microbiota profiles of SAMP8 mice at 1, 3, 7, and 10 months ( n = 6) using 16S rRNA sequencing. Alpha diversity (Shannon index) decreased significantly with age, while beta diversity revealed distinct clustering between young (1 and 3 months) and aged (7 and 10 months) SAMP8 mice. Firmicutes , Actinobacteria , and Deferribacteres declined significantly with age, whereas Proteobacteria and Bacteroidetes increased. At the genus level, Allobaculum and unclassified_f_Lachnospiraceae decreased significantly, whereas Ruminiclostridium_5 and Akkermansia increased significantly in older mice. Microbiota trajectory analysis identified four aging-related patterns. For biomarker discovery, the young (1 and 3 months, n = 12) and aged (7 and 10 months, n = 12) groups were compared using Random Forest analysis, which identified 11 key taxa, with Peptococcus exhibiting the highest diagnostic accuracy (area under the curve = 0.78). These findings highlight the dynamic microbiota shifts during aging and identify Peptococcus as a potential biomarker for aging, offering insights into microbiota-aging interactions and potential translational targets. IMPORTANCE: Aging is associated with profound changes in microbial composition, yet the precise trajectories and key microbial signatures of aging remain incompletely understood. This study provides a comprehensive analysis of gut microbiota dynamics in aging SAMP8 mice. By identifying significant shifts in microbial diversity, composition, and aging-related trajectories, our findings highlight the progressive restructuring of gut microbiota with age. Understanding these changes is critical for uncovering potential microbial biomarkers of aging, which could serve as diagnostic tools or therapeutic targets to promote healthy aging. Notably, we demonstrate that some key taxa, such as Peptococcus , can differentiate young and aged microbiomes with high accuracy, offering insights into the potential role of gut microbiota in aging-related health decline. These findings provide a foundation for future research aimed at microbiota-targeted interventions, such as probiotics or dietary modifications, to mitigate age-associated diseases and improve lifespan and health span.