A recent study published in the journal Nature Aging examined the impact of gut microbiota-derived phenylacetylglutamine (PAGln) on cellular senescence and aging. Conducted by a team from China, the research revealed that age-related changes in gut microbiota elevate PAGln levels, which are linked to mitochondrial dysfunction and DNA damage.
The study found a J-shaped correlation between PAGln levels and age, with significant increases noted in individuals over 60. Researchers analyzed plasma and fecal samples from 22 to 104-year-olds, employing in vitro, in vivo, and analytical methods to investigate PAGln's role in cellular senescence.
In vitro studies showed that treating human cells with PAGln resulted in increased cellular senescence markers. In vivo experiments using murine models demonstrated that chronic exposure to PAGln led to cellular senescence in kidney and lung tissues.
Moreover, the study identified bacterial species such as Clostridium scindens and Gordonibacter pamelaeae as key contributors to phenylacetic acid production, a precursor to PAGln. Pharmacological interventions targeting adrenoreceptor signaling effectively reduced PAGln-induced senescence.
In conclusion, the findings indicate that PAGln significantly contributes to cellular senescence and aging, presenting potential therapeutic targets to mitigate age-related decline.