Abstract
Inflammaging refers to chronic, low-grade inflammation during aging, which contributes to the pathogenesis of age-related diseases. Studies have shown that probiotic intervention in the aging stage could delay aging-related disorders. However, whether the application of probiotics in early life could have antiaging effects on offspring was unknown. Here, we investigated the effects of Lactobacillus rhamnosus GG (LGG) colonization in early life on inflammaging of offspring. Pregnant mice with the same conception time were given LGG live bacteria (LC group) or LGG fixed bacteria (NC group) from the 18th day after pregnancy until natural birth. The progeny mice were treated with 107 cfu of live or fixed LGG for 0-5 days after birth, respectively. LGG colonization could be detected in the feces of 3-week offspring. The 16S rRNA sequencing analysis of 3-week-old offspring showed that colonization of LGG in early life could alter the composition and diversity of gut microbiota. Interestingly, the beneficial effects of LGG colonization in early life on the microbiota lasted to 8 months old. The abundance of longevity-related bacteria (Lactobacillus, Bifidobacterium, and Akkermansia muciniphila) increased significantly in the LGG colonization group. In addition, LGG colonization increased the abundance of short-chain fatty acid- (SCFA-) producing bacteria and the production of cecal SCFAs. LGG colonization in early life protected the intestinal barrier, enhanced antioxidant defense, attenuated epithelial cell DNA damage, and inhibited intestinal low-grade inflammation in 8-month-old progeny mice. Mechanically, LGG could upregulate Sirtuin1 (SIRT1)/Adenosine 5′-monophosphate-activated protein kinase (AMPK)/Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) pathway and repress activation of nuclear factor-kappa B (NF-κB), while the protective effect of LGG was blunted after SIRT1 gene silencing. Together, LGG colonization in early life could ameliorate inflammaging of offspring, which would provide a new strategy for the prevention of age-related diseases.
Highlights
Aging is a complex process characterized by a continuous and progressive decline in physiological function and adaptive capacity, which increases the incidence of cancer and many chronic diseases [1, 2]
polymerase chain reaction (PCR) analysis was performed to detect the colonization of Lactobacillus rhamnosus GG (LGG), and we found that the specific bands of LGG were revealed by the migration spectrum of PCR products from fecal bacterial cultures of 3-week-old mice treated with live LGG (Figure 1(b))
These results indicated that LGG colonization in early life promoted the intestinal development of the offspring
Summary
Aging is a complex process characterized by a continuous and progressive decline in physiological function and adaptive capacity, which increases the incidence of cancer and many chronic diseases [1, 2]. It is commonly believed that healthy aging and longevity are modulated by complex interactions between genetic and nongenetic (e.g., lifestyle, sociodemographics, and living situation) factors [3, 4], both of which are closely related to the gut microbiota. The stability of gut microbiota may fluctuate with aging-related factors such as physiologic, lifestyle, and health status [8]. The microbiota diversity of the elderly is reduced, and the composition of the microbiota varies greatly among individuals [9]. These findings emphasize the crucial role of the microbial community in early life on regulating health status and lifespan
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