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Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts. | LitMetric

Amyotrophic lateral sclerosis alters the metabolic aging profile in patient derived fibroblasts.

Neurobiol Aging

Department of Neuroscience, Sheffield Institute for Translational Neuroscience (SITraN), University of Sheffield, Sheffield, UK. Electronic address:

Published: September 2021

AI Article Synopsis

  • * ALS fibroblasts show an altered metabolic profile with reduced NADH metabolism linked to age, disease onset, and death, while healthy controls exhibit increased NADH metabolism as they age.
  • * Supplementing specific metabolites like inosine and α-ketoglutaric acid in ALS fibroblasts may help improve energy production and counteract age-related metabolic issues.

Article Abstract

Aging is a major risk factor for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). As metabolic alterations are a hallmark of aging and have previously been observed in ALS, it is important to examine the effect of aging in the context of ALS metabolic function. Here, using a newly established phenotypic metabolic approach, we examined the effect of aging on the metabolic profile of fibroblasts derived from ALS cases compared to controls. We found that ALS fibroblasts have an altered metabolic profile, which is influenced by age. In control cases, we found significant increases with age in NADH metabolism in the presence of several metabolites including lactic acid, trehalose, uridine and fructose, which was not recapitulated in ALS cases. Conversely, we found a reduction of NADH metabolism with age of biopsy, age of onset and age of death in the presence of glycogen in the ALS cohort. Furthermore, we found that NADH production correlated with disease progression rates in relation to a number of metabolites including inosine and α-ketoglutaric acid. Inosine or α-ketoglutaric acid supplementation in ALS fibroblasts was bioenergetically favourable. Overall, we found aging related defects in energy substrates that feed carbon into glycolysis at various points as well as the tricarboxylic acid (TCA) cycle in ALS fibroblasts, which was validated in induced neuronal progenitor cell derived iAstrocytes. Our results suggest that supplementing those pathways may protect against age related metabolic dysfunction in ALS.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8346650PMC
http://dx.doi.org/10.1016/j.neurobiolaging.2021.04.013DOI Listing

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