The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans.

By Javier Apfeld, G. O'Connor, Thomas McDonagh, P. Distefano, R. Curtis. Genes & Development, 2004

652 citations recorded by the source corpus.

Although limiting energy availability extends lifespan in many organisms, it is not understood how lifespan is coupled to energy levels. We find that the AMP:ATP ratio, a measure of energy levels, increases with age in Caenorhabditis elegans and can be used to predict life expectancy. The C. elegans AMP-activated protein kinase alpha subunit AAK-2 is activated by AMP and functions to extend lifespan. In addition, either an environmental stressor that increases the AMP:ATP ratio or mutations that lower insulin-like signaling extend lifespan in an aak-2-dependent manner. Thus, AAK-2 is a sensor that couples lifespan to information about energy levels and insulin-like signals.

Subfields: Aging, Endocrine and Autonomic Systems

View Paper: https://www.semanticscholar.org/paper/524db45770ea489fc2a302f852040b6bd3f14328

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Aging

1. D. Hardie
2. R. Shaw
3. A. Brunet
4. G. Lithgow
5. Rute Martins
6. W. Link
7. E. L. Greer
8. Steven P. Gygi

In Endocrine and Autonomic Systems

1. G. Lithgow
2. Rute Martins
3. W. Link
4. A. Brunet
5. E. L. Greer
6. Steven P. Gygi
7. J. Villén
8. Johan Auwerx

Citations in the corpus

• Nonequilibrium physics in biology (2019, result): “Further analysis of the ageing and rejuvenation attractors suggests that self-degradation of lifespan-limiting and longevity-promoting genes leads to an increased stability of the ageing and rejuvenation states, respectively, which is consistent with experiments (Apfeld et al., 2004; Kenyon et al., ”
• How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). (2010, background): “This kinase was previously established as a sensor of cellular energy depletion in both mammals (Hardie et al., 2006) and specifically C. elegans (Apfeld et al., 2004; Greer et al., 2007), and has been found to induce a health-promoting metabolic state particularly by inducing mitochondrial…”
• Long live FOXO: unraveling the role of FOXO proteins in aging and longevity (2015, background): “…kinase), an energy sensor for cellular AMP/ATP ratio that enables catabolic reactions for energy gain, has been shown to respond to dietary restriction by increasing stress resistance and extending longevity in C. elegans in a DAF-16/FOXO-dependent manner (Apfeld et al., 2004; Greer et al., 2007a).”
• The plasticity of aging: insights from long-lived mutants. (2005, background): “In l oaddition, the AMP kinase subunit AAK-2 is completely required for transient heat stress—which lowers energy r tlevels—to increase life span (Apfeld et al., 2004).”
• An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans. (2007, background): “reported that mutating one of the AMPK catalytic subunits, aak-2, in conjunction with mutating daf-16 decreased worm lifespan further than mutating each gene individually [15].”