Uridine has been identified as a pro-regenerative metabolite, presenting new avenues for metabolic intervention in tissue regeneration and ageing.
Regeneration is the reproduction or replacement of damaged, diseased, or aged tissues. Across animal species, everyone possesses a certain degree of regeneration. This regenerative capacity varies across species and unlike stem cells from regenerative tissues of axolotl limbs or deer antlers, human stem cells have a relatively limited capacity for regenerative repair that declines with age. Much remains to be known about whether molecular characteristics between these naturally-occurring regeneration processes are evolutionarily conserved across species.
Comparing the similarities and differences between species allows us to learn about regulatory mechanisms that underline vital life events like regeneration. For this to work, there needs to be comparable and enough overlapping factors across different samples, and because the structures of metabolites are largely similar across species, metabolism is an ideal area to look into evolutionarily conserved biology. However, little is known about the small molecule metabolites that could be regulating ageing and regeneration processes.
Recently, researchers from the Institute of Zoology and Beijing Institute of Genomics of the Chinese Academy of Sciences have collaborated to identify uridine as a pro-regenerative metabolite that promoted human stem cell activity and enhanced regeneration and tissue repair in multiple tissues in mammals.
Here, the team combined metabolomics and transcriptomics approaches to reveal several cross-species and cross-ages metabolic programmes associated with higher regenerative capacity.
Together with the human stem cell ageing research system, the researchers screened for natural metabolite candidates with regeneration-promoting potentials and found that uridine counteracted cellular senescence in both physiologically and pathologically senescent cells. They observed that adding uridine promoted regeneration or repair of various tissues in vivo, including skeletal, muscle, heart, liver, skin, and artificial cartilage. Particularly in the muscle injury model, uridine was seen to effectively improve muscle regeneration and repair, relieved inflammatory response, and provided uridine-treated mice with higher grip strength and locomotive activity.
Furthermore, the team found that uridine was more abundant in the plasma of young individuals than older individuals and that oral uridine treatment improved the physical activities of physiologically aged mice.
This study has demonstrated that the treatment of uridine can alleviate stem cell senescence, promote tissue regeneration and repair, and improve the physical activities of old mice. This enlightens us to previously unknown metabolism-associated regeneration principles across species and presents new avenues for metabolic intervention in tissue repair, regeneration, and ageing.
Source: Liu et al. (2022). Cross-species metabolomic analysis identifies uridine as a potent regeneration promoting factor. Cell discovery, 8(1), 1-22.