hif-1;vhl-1

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.