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A gene-expression-based neural code for food abundance that modulates lifespan.

Entchev EV, Patel DS, Zhan M, Steele AJ, Lu H, Ch'ng Q - Elife (2015)

Bottom Line: These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses.This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan.Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

ABSTRACT
How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGFβ and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

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Effects of DR initiation time, temperature and egg-5(RNAi) on the lifespan response.(A) Survival curves for worms transferred from the baseline, abundant level of food (2 × 109 cells/ml) to a more limited food condition (2 × 105 cells/ml) at different days of adulthood. Different days of DR initiation result in substantial differences in survival trajectories. (B) The mean lifespan response of these worms shows lifespan extension for animals transferred on day 2 or later but a negative effect on lifespan for animals subjected to DR from day 1 of adulthood, possibly due to developmental effects. (C) Wildtype worms show a similar lifespan response to exposed different food levels in the absence of egg-5(RNAi). (D) The pattern of lifespan modulation by food abundance is maintained across the range of standard C. elegans culture temperatures. (E) Increased temperature consistently lowers mean lifespans across all food levels. (F) Increased temperature also consistently lowers the range of lifespan modulation achieved by alterations in food.DOI:http://dx.doi.org/10.7554/eLife.06259.007
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fig1s1: Effects of DR initiation time, temperature and egg-5(RNAi) on the lifespan response.(A) Survival curves for worms transferred from the baseline, abundant level of food (2 × 109 cells/ml) to a more limited food condition (2 × 105 cells/ml) at different days of adulthood. Different days of DR initiation result in substantial differences in survival trajectories. (B) The mean lifespan response of these worms shows lifespan extension for animals transferred on day 2 or later but a negative effect on lifespan for animals subjected to DR from day 1 of adulthood, possibly due to developmental effects. (C) Wildtype worms show a similar lifespan response to exposed different food levels in the absence of egg-5(RNAi). (D) The pattern of lifespan modulation by food abundance is maintained across the range of standard C. elegans culture temperatures. (E) Increased temperature consistently lowers mean lifespans across all food levels. (F) Increased temperature also consistently lowers the range of lifespan modulation achieved by alterations in food.DOI:http://dx.doi.org/10.7554/eLife.06259.007

Mentions: During DR, lifespan increases as food levels are decreased from ad libitum conditions until reaching a maximum, beyond which further food reduction lowers lifespan (Bishop and Guarente, 2007; Mair and Dillin, 2008; Fontana et al., 2010; Alic and Partridge, 2011). To fully understand the response to food levels that C. elegans might encounter in the wild (Felix and Duveau, 2012), we modified a well-established DR protocol (Greer et al., 2007) (Figure 1A) to measure the lifespans of wildtype animals shifted as day 2 adults to 19 concentrations of the Escherichia coli food source across ∼11 orders of magnitude (Figure 1B, Figure 1—figure supplement 1 and Figure 1—source data 1). We inhibited progeny production with egg-5(RNAi) (Figure 1A) to prevent matricide due to internal hatching at low food levels. This treatment does not affect the lifespan response to food; similar responses were observed in wildtype animals without egg-5(RNAi) (Figure 1—figure supplement 1), and are found in the literature where similar subsets of food ranges were tested using other DR protocols (below).10.7554/eLife.06259.003Figure 1.Two neuronal genes, daf-7 and tph-1, shape a complex, multiphasic relationship between lifespan and food availability.


A gene-expression-based neural code for food abundance that modulates lifespan.

Entchev EV, Patel DS, Zhan M, Steele AJ, Lu H, Ch'ng Q - Elife (2015)

Effects of DR initiation time, temperature and egg-5(RNAi) on the lifespan response.(A) Survival curves for worms transferred from the baseline, abundant level of food (2 × 109 cells/ml) to a more limited food condition (2 × 105 cells/ml) at different days of adulthood. Different days of DR initiation result in substantial differences in survival trajectories. (B) The mean lifespan response of these worms shows lifespan extension for animals transferred on day 2 or later but a negative effect on lifespan for animals subjected to DR from day 1 of adulthood, possibly due to developmental effects. (C) Wildtype worms show a similar lifespan response to exposed different food levels in the absence of egg-5(RNAi). (D) The pattern of lifespan modulation by food abundance is maintained across the range of standard C. elegans culture temperatures. (E) Increased temperature consistently lowers mean lifespans across all food levels. (F) Increased temperature also consistently lowers the range of lifespan modulation achieved by alterations in food.DOI:http://dx.doi.org/10.7554/eLife.06259.007
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4417936&req=5

fig1s1: Effects of DR initiation time, temperature and egg-5(RNAi) on the lifespan response.(A) Survival curves for worms transferred from the baseline, abundant level of food (2 × 109 cells/ml) to a more limited food condition (2 × 105 cells/ml) at different days of adulthood. Different days of DR initiation result in substantial differences in survival trajectories. (B) The mean lifespan response of these worms shows lifespan extension for animals transferred on day 2 or later but a negative effect on lifespan for animals subjected to DR from day 1 of adulthood, possibly due to developmental effects. (C) Wildtype worms show a similar lifespan response to exposed different food levels in the absence of egg-5(RNAi). (D) The pattern of lifespan modulation by food abundance is maintained across the range of standard C. elegans culture temperatures. (E) Increased temperature consistently lowers mean lifespans across all food levels. (F) Increased temperature also consistently lowers the range of lifespan modulation achieved by alterations in food.DOI:http://dx.doi.org/10.7554/eLife.06259.007
Mentions: During DR, lifespan increases as food levels are decreased from ad libitum conditions until reaching a maximum, beyond which further food reduction lowers lifespan (Bishop and Guarente, 2007; Mair and Dillin, 2008; Fontana et al., 2010; Alic and Partridge, 2011). To fully understand the response to food levels that C. elegans might encounter in the wild (Felix and Duveau, 2012), we modified a well-established DR protocol (Greer et al., 2007) (Figure 1A) to measure the lifespans of wildtype animals shifted as day 2 adults to 19 concentrations of the Escherichia coli food source across ∼11 orders of magnitude (Figure 1B, Figure 1—figure supplement 1 and Figure 1—source data 1). We inhibited progeny production with egg-5(RNAi) (Figure 1A) to prevent matricide due to internal hatching at low food levels. This treatment does not affect the lifespan response to food; similar responses were observed in wildtype animals without egg-5(RNAi) (Figure 1—figure supplement 1), and are found in the literature where similar subsets of food ranges were tested using other DR protocols (below).10.7554/eLife.06259.003Figure 1.Two neuronal genes, daf-7 and tph-1, shape a complex, multiphasic relationship between lifespan and food availability.

Bottom Line: These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses.This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan.Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

View Article: PubMed Central - PubMed

Affiliation: MRC Centre for Developmental Neurobiology, King's College London, London, United Kingdom.

ABSTRACT
How the nervous system internally represents environmental food availability is poorly understood. Here, we show that quantitative information about food abundance is encoded by combinatorial neuron-specific gene-expression of conserved TGFβ and serotonin pathway components in Caenorhabditis elegans. Crosstalk and auto-regulation between these pathways alters the shape, dynamic range, and population variance of the gene-expression responses of daf-7 (TGFβ) and tph-1 (tryptophan hydroxylase) to food availability. These intricate regulatory features provide distinct mechanisms for TGFβ and serotonin signaling to tune the accuracy of this multi-neuron code: daf-7 primarily regulates gene-expression variability, while tph-1 primarily regulates the dynamic range of gene-expression responses. This code is functional because daf-7 and tph-1 mutations bidirectionally attenuate food level-dependent changes in lifespan. Our results reveal a neural code for food abundance and demonstrate that gene expression serves as an additional layer of information processing in the nervous system to control long-term physiology.

Show MeSH
Related in: MedlinePlus