Metabolome and proteome changes with aging in Caenorhabditis elegans

Abstract

To expand the understanding of aging in the model organism Caenorhabditis elegans, global quantification of metabolite and protein levels in young and aged nematodes was performed using mass spectrometry. With age there was a decreased abundance of proteins functioning in transcription termination, mRNA degradation, mRNA stability, protein synthesis, and proteasomal function. Furthermore there was altered S-adenosyl methionine metabolism as well as a decreased abundance of the S-adenosyl methionine synthetase (SAMS-1) protein. Other aging-related changes included alterations in free fatty acid levels and composition, decreased levels of ribosomal proteins, decreased levels of NADP-dependent isocitrate dehydrogenase (IDH1), a shift in the cellular redox state, an increase in sorbitol content, alterations in free amino acid levels, and indications of altered muscle function and sarcoplasmic reticulum Ca2+ homeostasis. There were also decreases in pyrimidine and purine metabolite levels, most markedly nitrogenous bases. Supplementing the culture medium with cytidine (a pyrimidine nucleoside) or hypoxanthine (a purine base) increased lifespan slightly, suggesting that aging-induced alterations in ribonucleotide metabolism affect lifespan. An age-related increase in body size, lipotoxicity from ectopic yolk lipoprotein accumulation, a decline in NAD+ levels, and mitochondrial electron transport chain dysfunction may explain many of these changes. In addition, dietary restriction in aged worms resulting from sarcopenia of the pharyngeal pump likely decreases the abundance of SAMS-1, possibly leading to decreased phosphatidylcholine levels, larger lipid droplets, and ER and mitochondrial stress. The complementary use of proteomics and metabolomics yielded unique insights into the molecular processes altered with age in C. elegans.

Age‐dependent changes and biomarkers of aging in Caenorhabditis elegans

“…During aging, proteins that likely function in nucleosome assembly, ER‐nuclear signaling, and the response to unfolded proteins increase, whereas the abundance of proteins involved in metabolism such as fatty acid, carbohydrate, and amino acid metabolism decreases (Narayan et al, ). A similar observation has been reported showing that overall levels of fatty acid metabolic proteins decrease (Copes et al, ). Because altering fat metabolism has huge impacts on aging and lifespan (Lee et al, ; Lemieux & Ashrafi, ), the proper maintenance of fat metabolism in old age will be beneficial for longevity.…”

Aging Skeletal Muscle Proteomics Finds Changes in Spliceosome, Immune factors, Proteostasis and Mitochondria

“…Of 22 proteins quantified for TCA cycle, only malate dehydrogenase (MDH1), isocitrate dehydrogenase (IDH1), fumarate hydratase (FH) and succinate--CoA ligase (SUCLG1) ( Figure S3C) were significantly lower at older ages. The decreasing levels of IDH-1 with age is unsurprising, as previous studies have shown a decrease in abundance of IDH-1 in older C.elegans 38 . IDH1 converts isocitrate to α-ketoglutarate by reducing NADP to NADPH in the process.…”

Proteomic pipeline to identify age-related compositional and structural changes of the human dentin extracellular matrix

“…3A), indicating a higher variability in samples of intermediate solubility.We found that extracts obtained from older individuals showed a total number of ECM proteins of 158 in E-extracts, 127 in G-extracts, and 156 in D-extracts. A greater variability was seen in D-extracts (84), when compared to E-(72) and G-extracts(58) (Fig. 3B).…”