Age-associated Akkermansia muciniphila decline links to brown adipose tissue aging: AKK supplementation improves BAT...

Aging is associated with metabolic decline, brown adipose tissue (BAT) dysfunction, and remodelling of the gut microbiota. Akkermansia muciniphila (AKK) has been implicated in metabolic regulation; however, its relationship with BAT aging remains unclear. This study aims to investigate whether age-associated AKK depletion is linked to BAT aging and whether AKK supplementation attenuates aging phenotypes in BAT. Male mice aged 7 weeks, 7 months, and 11 months were analysed to characterise age-related changes in gut microbiota and BAT. 16S rRNA sequencing was performed to assess microbial composition. BAT morphology, thermogenic gene expression, and senescence markers were evaluated by histology, immunofluorescence, western blotting, and quantitative PCR. In a separate experiment, 11-month-old mice received live AKK supplementation for 30 days. Analysis of covariance was conducted to adjust for body weight where appropriate. Aging was accompanied by reduced microbial diversity and progressive depletion of AKK. BAT from older mice exhibited increased expression of senescence-associated genes, enlarged lipid droplets, and reduced thermogenic markers. AKK abundance was negatively correlated with BAT senescence markers. Supplementation with live AKK in middle-aged mice was associated with reduced Cdkn1a expression and increased thermogenic gene expression in BAT. These associations remained significant after adjustment for body weight. Aging in mice is accompanied by gut microbiota remodelling characterised by AKK decline and concurrent BAT aging phenotypes. AKK supplementation is associated with partial attenuation of BAT aging markers. These findings support a link between age-related microbial shifts and adipose tissue aging.