hif-1;vhl-1

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Diet
OP50;NGM
Lifespan (days)
22.0
Lifespan change (compared to wild type)
-3.51%
Phenotype
Vhl-1(ok161) animals are significantly longer-lived than wild type (N2) animals; vhl-1(ok161) hif-1(ia4) double mutant animals are not longer-lived than N2.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 22.0 days, while single mutant hif-1(ia4) has a lifespan of 20.0 days, single mutant vhl-1(ok161) has a lifespan of 30.0 days and wild type has a lifespan of 22.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Mehta R et al., 2009, Proteasomal regulation of the hypoxic response modulates aging in C. elegans. Science. 324(5931):1196-8 19372390 Click here to select all mutants from this PubMed ID in the graph
Abstract
The Caenorhabditis elegans von Hippel-Lindau tumor suppressor homolog VHL-1 is a cullin E3 ubiquitin ligase that negatively regulates the hypoxic response by promoting ubiquitination and degradation of the hypoxic response transcription factor HIF-1. Here, we report that loss of VHL-1 significantly increased life span and enhanced resistance to polyglutamine and beta-amyloid toxicity. Deletion of HIF-1 was epistatic to VHL-1, indicating that HIF-1 acts downstream of VHL-1 to modulate aging and proteotoxicity. VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin-like signaling. These findings define VHL-1 and the hypoxic response as an alternative longevity and protein homeostasis pathway.

Temperature °C
25
Diet
NGM
Lifespan (days)
21.5
Lifespan change (compared to wild type)
19.18%
Phenotype
The hif-1(ia4) animals lived significantly longer than N2 animals at 25°C. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 25°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 25°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 21.5 days, while single mutant vhl-1(ok161) has a lifespan of 25.53 days, single mutant hif-1(ia4) has a lifespan of 21.03 days and wild type has a lifespan of 18.04 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
25
Diet
NGM
Lifespan (days)
21.64
Lifespan change (compared to wild type)
28.20%
Phenotype
The hif-1(ia4) animals lived significantly longer than N2 animals at 25°C. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 25°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 25°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 21.64 days, while single mutant vhl-1(ok161) has a lifespan of 22.83 days, single mutant hif-1(ia4) has a lifespan of 19.53 days and wild type has a lifespan of 16.88 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
25
Diet
NGM
Lifespan (days)
21.51
Lifespan change (compared to wild type)
15.21%
Phenotype
The hif-1(ia4) animals lived significantly longer than N2 animals at 25°C. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 25°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 25°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 21.51 days, while single mutant vhl-1(ok161) has a lifespan of 25.94 days, single mutant hif-1(ia4) has a lifespan of 21.61 days and wild type has a lifespan of 18.67 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
25
Diet
NGM
Lifespan (days)
21.21
Lifespan change (compared to wild type)
5.37%
Phenotype
The hif-1(ia4) animals lived significantly longer than N2 animals at 25°C. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 25°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 25°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 21.21 days, while single mutant vhl-1(ok161) has a lifespan of 22.98 days, single mutant hif-1(ia4) has a lifespan of 21.85 days and wild type has a lifespan of 20.13 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
25
Diet
NGM
Lifespan (days)
21.53
Lifespan change (compared to wild type)
19.68%
Phenotype
The hif-1(ia4) animals lived significantly longer than N2 animals at 25°C. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 25°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 25°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 21.53 days, while single mutant vhl-1(ok161) has a lifespan of 24.28 days, single mutant hif-1(ia4) has a lifespan of 20.8 days and wild type has a lifespan of 17.99 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
25.93
Lifespan change (compared to wild type)
15.45%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 25.93 days, while single mutant vhl-1(ok161) has a lifespan of 31.51 days, single mutant hif-1(ia4) has a lifespan of 23.03 days and wild type has a lifespan of 22.46 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
25.6
Lifespan change (compared to wild type)
4.70%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 25.6 days, while single mutant vhl-1(ok161) has a lifespan of 32.81 days, single mutant hif-1(ia4) has a lifespan of 24.2 days and wild type has a lifespan of 24.45 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
23.9
Lifespan change (compared to wild type)
6.74%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 23.9 days, while single mutant vhl-1(ok161) has a lifespan of 27.43 days, single mutant hif-1(ia4) has a lifespan of 20.92 days and wild type has a lifespan of 22.39 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
25.06
Lifespan change (compared to wild type)
18.26%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 25.06 days, while single mutant vhl-1(ok161) has a lifespan of 26.38 days, single mutant hif-1(ia4) has a lifespan of 25.16 days and wild type has a lifespan of 21.19 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
25.49
Lifespan change (compared to wild type)
-1.96%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 25.49 days, while single mutant vhl-1(ok161) has a lifespan of 28.77 days, single mutant hif-1(ia4) has a lifespan of 21.56 days and wild type has a lifespan of 26.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
23.48
Lifespan change (compared to wild type)
3.57%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 23.48 days, while single mutant vhl-1(ok161) has a lifespan of 27.5 days, single mutant hif-1(ia4) has a lifespan of 21.89 days and wild type has a lifespan of 22.67 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
20
Diet
NGM
Lifespan (days)
25.25
Lifespan change (compared to wild type)
8.28%
Phenotype
At 20°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived 20°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals. The hif-1(ia4);vhl-1(ok161) animals were slightly longer-lived than hif-1(ia4) animals at 20°C.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 25.25 days, while single mutant vhl-1(ok161) has a lifespan of 30.31 days, single mutant hif-1(ia4) has a lifespan of 22.82 days and wild type has a lifespan of 23.32 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
15
Diet
NGM
Lifespan (days)
32.6
Lifespan change (compared to wild type)
4.92%
Phenotype
At 15°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 15°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 32.6 days, while single mutant vhl-1(ok161) has a lifespan of 45.45 days, single mutant hif-1(ia4) has a lifespan of 33.32 days and wild type has a lifespan of 31.07 days.
Type of interaction
See methods
Antagonistic (positive)
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
15
Diet
NGM
Lifespan (days)
35.17
Lifespan change (compared to wild type)
2.00%
Phenotype
At 15°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 15°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 35.17 days, while single mutant vhl-1(ok161) has a lifespan of 49.7 days, single mutant hif-1(ia4) has a lifespan of 34.9 days and wild type has a lifespan of 34.48 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
15
Diet
NGM
Lifespan (days)
30.74
Lifespan change (compared to wild type)
7.15%
Phenotype
At 15°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 15°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 30.74 days, while single mutant vhl-1(ok161) has a lifespan of 47.5 days, single mutant hif-1(ia4) has a lifespan of 28.47 days and wild type has a lifespan of 28.69 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
15
Diet
NGM
Lifespan (days)
37.04
Lifespan change (compared to wild type)
11.30%
Phenotype
At 15°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 15°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 37.04 days, while single mutant vhl-1(ok161) has a lifespan of 51.79 days, single mutant hif-1(ia4) has a lifespan of 31.56 days and wild type has a lifespan of 33.28 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Temperature °C
15
Diet
NGM
Lifespan (days)
33.36
Lifespan change (compared to wild type)
4.32%
Phenotype
At 15°C, the life span of hif-1(ia4) animals was not significantly different from N2 animals. In contrast to hif-1(ia4) animals, vhl-1(ok161) animals were long-lived at 15°C, relative to N2. At this temperature, vhl-1(ok161) animals were also significantly longer lived than hif-1(ia4) animals.
Lifespan comparisons
Double mutant hif-1(ia4);vhl-1(ok161) has a lifespan of 33.36 days, while single mutant vhl-1(ok161) has a lifespan of 48.51 days, single mutant hif-1(ia4) has a lifespan of 31.95 days and wild type has a lifespan of 31.98 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Leiser SF et al., 2011, HIF-1 modulates longevity and healthspan in a temperature-dependent manner. Aging Cell. 10(2):318-26 21241450 Click here to select all mutants from this PubMed ID in the graph
Abstract
The hypoxia-inducible factor HIF-1 has recently been identified as an important modifier of longevity in the roundworm Caenorhabditis elegans. Studies have reported that HIF-1 can function as both a positive and negative regulator of life span, and several disparate models have been proposed for the role of HIF in aging. Here, we resolve many of the apparent discrepancies between these studies. We find that stabilization of HIF-1 increases life span robustly under all conditions tested; however, deletion of hif-1 increases life span in a temperature-dependent manner. Animals lacking HIF-1 are long lived at 25°C but not at 15°C. We further report that deletion or RNAi knockdown of hif-1 impairs healthspan at lower temperatures because of an age-dependent loss of vulval integrity. Deletion of hif-1 extends life span modestly at 20°C when animals displaying the vulval integrity defect are censored from the experimental data, but fails to extend life span if these animals are included. Knockdown of hif-1 results in nuclear relocalization of the FOXO transcription factor DAF-16, and DAF-16 is required for life span extension from deletion of hif-1 at all temperatures regardless of censoring.

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Clk;Vhl
Mus musculus	Vhl;Clk

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Clk
Mus musculus	Epas1
Mus musculus	Hif3a
Mus musculus	Hif1a

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Vhl

hif-1;vhl-1

Genetic mutants with hif-1, vhl-1 alterations