Skin Rejuvenation in Aged Mice by Fecal Microbiota Transplantation from Young Mice Feces

Skin aging is an increasingly prominent topic in the context of healthy aging.During the aging process,the skin’s barrier function diminishes,its water content decreases,wrinkles begin to form,and changes occur in the gut microbiota composition.However,the relationship between gut microbiota and skin aging remains unclear.In this study,we explored skin rejuvenation in aged mice through fecal microbiota trans-plantation(FMT)using feces from young mice.The results demonstrated enhanced water retention,thick-ened stratum corneum,increased collagen content,and improved epithelial cell differentiation in aged mice following FMT.Notably,FMT particularly increased the abundance of Lactobacillus and Lactococcus in aged mice,which were nearly undetectable in untreated aged mice.Non-targeted and targeted meta-bolomics analyses indicated that FMT significantly elevated levels of tryptophan(Trp)and its microbiota metabolites(e.g.,indole-3-lactic acid(ILA))in the feces and serum of aged mice.Both Trp and ILA appeared to rejuvenate aged skin by activating the aryl hydrocarbon receptor(AhR)to promote epidermal cell dif-ferentiation.In conclusion,FMT from young mice rejuvenated aged skin via Trp-metabolizing bacteria(Lactobacillus and Lactococcus)and Trp-derived metabolites,suggesting that interventions targeting Trp metabolites may effectively improve skin aging.

PAI-1 Derived from Alveolar Type 2 Cells Drives Aging-Associated Pulmonary Fibrosis

Pulmonary fibrosis(PF)is a lethal lung disease that predominantly affects older adults;however,whether and how aging triggers fibrosis remains unclear.To pinpoint the predominant initiating factors of PF,we first analyzed single-cell RNA sequencing(scRNA-seq)data from the lung tissues of 45 normal donors and 51 PF patients and found that aging might serve as the primary catalyst for PF development.To further investigate the influence of aging on PF formation,we conducted a comprehensive and thorough study employing a natural aging mouse model.We found that dynamic alterations in the quantity and types of collagen fibers during aging-induced PF progression,especially in collagenous(Col)I,emerged as the predominant driver of PF.We then investigated the regulation of Col I synthesis during aging using primary alveolar type 2(AT2)cells and A549 cells line through conditioned media and Transwell cocul-ture,and found that secretions—particularly plasminogen activator inhibitor(PAI)-1—from aged AT2 cells promoted fibrosis and enhanced collagen type I alpha 1(Col1al)production via the transforming growth factor(TGF)-b/small mother against decapentaplegic(Smad)2/3 pathway.Furthermore,scRNA-seq and a histological analysis of human lung tissue demonstrated a significant upregulation of SERPINE1(the gene encoding PAI-1)and PAI-1 expression in both aging lung tissue and AT2 cells,which was consistent with our findings from animal experiments,providing additional evidence for the pivotal role of PAI-1 during aging and the development of PF.Our research demonstrates that PAI-1,a crucial factor secreted by aging AT2 cells,exerts a pivotal role in promoting the synthesis of Col1a1 in fibroblasts,subsequently leading to Col I deposition,and in driving the progression of PF by mediating the TGF-b/Smad2/3 pathway.Our find-ings offer critical evidence for the involvement of epithelial dysfunction in age-related PF and provides potential novel therapeutic targets for clinical intervention.