Alpha-ketoglutarate (AKG) is a key molecule in the Krebs cycle determining the overall rate of the citric acid cycle of the organism. It is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. AKG as a precursor of glutamate and glutamine is a central metabolic fuel for cells of the gastrointestinal tract as well. AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in the skeletal muscles and can be used in clinical applications. In addition to these health benefits, a recent study has shown that AKG can extend the lifespan of adult Caenorhabditis elegans by inhibiting ATP synthase and TOR. AKG not only extends lifespan, but also delays age-related disease. In this review, we will summarize the advances in AKG research field, in the content of its physiological functions and applications.
Uncovering genetic variation through resequencing is limited by the fact that only sequences with similarity to the reference genome are examined. Reference genomes are often incomplete and cannot represent the full range of genetic diversity as a result of geographical divergence and independent demographic events. To more comprehensively characterize genetic variation of pigs (Sus scrofa), we generated de novo assemblies of nine geographically and phenotypically representative pigs from Eurasia. By comparing them to the reference pig assembly, we uncovered a substantial number of novel SNPs and structural variants, as well as 137.02-Mb sequences harboring 1737 protein-coding genes that were absent in the reference assembly, revealing variants left by selection. Our results illustrate the power of whole-genome de novo sequencing relative to resequencing and provide valuable genetic resources that enable effective use of pigs in both agricultural production and biomedical research.
Knowledge about the impact of different geographical environments on rhesus macaque gut microbiota is limited. In this study, we compared the characteristics of gut microbiota in six different Chinese rhesus macaque populations, including Hainan, Nanning, Guizhou, Xichang, Jianchuan and Tibet. Through the composition analysis of operational taxonomic units (OTUs), we found that there were significant differences in the abundance of core overlapping OTUs in the six Chinese groups. Specifically, the Tibet population exhibited the highest gut microbial diversity and the most unique OTUs. Statistically significant differences in the composition of gut microbiota among the six groups at phylum and family level were evident. Specifically, Tibet had higher abundances of Firmicutes and lower abundances of Bacteroidetes than the other geographical groups, and the higher abundance of Firmicutes in the Tibetan group was mainly caused by a significant increase in the family Ruminococcaceae and Christensenellaceae. Phylogenetic investigation of communities by reconstruction of unobserved state analysis showed that the enrichment ratio for environmental information processing and organismal systems was the highest in the Tibet population. Additionally, our results suggested that in the adaptation process of rhesus macaques to different geographical environments, the abundance of the core common flora of the intestinal microbes had undergone varying degree of change and produced new and unique flora, both of which helped to reshape the gut microbiota of rhesus macaques. In particular, this change was more obvious for animals in the high-altitude environments.
Alpha-ketoglutarate (AKG) is a key metabolite of the tricarboxylic acid (TCA) cycle, an essential process influencing the mitochondrial oxidative respiration rate. Recent studies have shown that dietary AKG reduces mTOR pathway activation by inhibiting ATP synthase, thereby extending the lifespan of nematodes. Although AKG also extends lifespan in fruit flies, the antiaging mechanisms of AKG in these organisms remain unclear. In the present study, we explored changes in gene expression associated with the extension of
Drosophila
lifespan mediated by dietary AKG. Supplementation of the flies’ diets with 5 μM AKG extended their lifespan but reduced their reproductive performance. Dietary AKG also enhanced vertical climbing ability, but did not protect against oxidative stress or increase tolerance to starvation. AKG-reared flies were resistant to heat stress and demonstrated higher expression of heat shock protein genes (
Hsp22
and
Hsp70
) than control flies. In addition, AKG significantly upregulated mRNA expression of
cry
,
FoxO
,
HNF4
,
p300
,
Sirt1
and
AMPKα
, and downregulated expression of
HDAC4
,
PI3K
,
TORC
,
PGC
, and
SREBP
. The metabolic effects of AKG supplementation included a reduction in the ATP/ADP ratio and increased autophagy. Collectively, these observations indicate that AKG extends
Drosophila
lifespan by activating AMPK signaling and inhibiting the mTOR pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.