Another longevity-related biochemical pathway

Another cross-species pathway has been discovered that allows interventions to lengthen life in primitive organisms, C. elegans nematode worms in this case.  The pathway is related to the hypoxic response, how cells respond to protect themselves when there is insufficient oxygen.  It turns out that if the hypoxic response can be turned on when normal oxygen is present, nematodes live significantly longer.  A recent research report indicates that this was experimentally accomplished by breeding nematodes that could not produce the protein VHL-1which destroys another protein called HIF which keeps the hypoxic response turned off when oxygen is present.  Also, it appears that the cells in such long-lived nematodes are relatively free of lipofuscin and toxic age-related protein aggregations such as seen in Alzheimer’s, Huntington’s and other age-related diseases(ref).  So, as is the case for dietary restriction the increase appears to be not only in lifespan but also in healthspan.  The hypoxic response pathway is different than that which is involved in calorie restriction.  “VHL-1 and HIF-1 control longevity by a mechanism distinct from both dietary restriction and insulin/IGF-1-like signaling.”  As of yet, however, just how HIF works downstream to extend longevity is still unclear.  The hypoxic response appears to operate in higher animals as well, including humans.  However, Dr. Matt Kaeberlein, University of Washington assistant professor of pathology and the senior author on the study is reported to caution that “mutation of VHL-1 is associated with a variety of tumors, and any therapies targeted toward activation of HIF would most likely need to be specific for cells that are not rapidly dividing, such as brain cells or muscle cells.”  It is too early to know if a practical human anti-aging intervention can be tied to the hypoxic response but the possibility is intriguing.