Alternative Mitochondrial Fuel Extends Life Span

Departments of Pathology and Genetics, Yale University School of Medicine, New Haven, CT 06520-8023, USA.
Cell metabolism (Impact Factor: 17.57). 04/2012; 15(4):417-8. DOI: 10.1016/j.cmet.2012.03.011
Source: PubMed


In this issue of Cell Metabolism, Ristow and colleagues (Zarse et al., 2012) elucidate a conserved mechanism through which reduced insulin-IGF1 signaling activates an AMP-kinase-driven metabolic shift toward oxidative proline metabolism. This, in turn, produces an adaptive mitochondrial ROS signal that extends worm life span. These findings further bolster the concept of mitohormesis as a critical component of conserved aging and longevity pathways.

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Available from: Elizabeth A Schroeder, Jun 08, 2015
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    • "As mentioned above, ROS have been associated with cellular damage. However, diverse studies have challenged the concept of ROS as simply detrimental; instead, they have been proposed as second messengers that trigger a program of transcriptional and metabolic shifts that initiate an adaptive ROS signaling response to attenuate the adverse effects of oxidative stress [92, 93]. Positive effects of ROS have been detected in both humans and C. elegans. "
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    ABSTRACT: Recent research suggests that chromatin-modifying enzymes are metabolic sensors regulating gene expression. Epigenetics is linked to metabolomics in response to the cellular microenvironment. Specific metabolites involved in this sensing mechanism include S-adenosylmethionine, acetyl-CoA, alphaketoglutarate and NAD (+) . Although the core metabolic pathways involving glucose have been emphasized as the source of these metabolites, the reprogramming of pathways involving non-essential amino acids may also play an important role, especially in cancer. Examples include metabolic pathways for glutamine, serine and glycine. The coupling of these pathways to the intermediates affecting epigenetic regulation occurs by "parametabolic" mechanisms. The metabolism of proline may play a special role in this parametabolic linkage between metabolism and epigenetics. Both proline degradation and biosynthesis are robustly affected by oncogenes or suppressor genes, and they can modulate intermediates involved in epigenetic regulation. A number of mechanisms in a variety of animal species have been described by our laboratory and by others. The challenge we now face is to identify the specific chromatin-modifying enzymes involved in coupling of proline metabolism to altered reprogramming of gene expression.
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