Thanks again to Res for suggesting the lead which led to this post.
Adding to the list of rare genetic disorders affecting longevity recently discussed in this Blog, there is Wolfram Syndrome. This is a disease long known to be associated with mitochondrial dysfunction that leads to a complex of symptoms including Type 1 diabetes and problems with eyesight and hearing. Wolfram Syndrome 1 is caused by mutations in the WFS1 gene. Recently reported research points to a novel gene CISD2, whose deficiency leads to Wolfram Syndrome 2 (WFS2). The gene is located on chromosome 4q which is known to be a candidate region for human longevity genes(ref). The new research using CISD2 knockout mice shows “ — that CISD2 is involved in mammalian life-span control. Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, and these events precede the two earliest manifestations of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging(ref).’ the authors of the study suggest “that mutation of CISD2 causes the mitochondria-mediated disorder WFS2 in humans.”
I have previously discussed so-called longevity genes, mTOR in particular. It seems more concise to describe genes that accelerate aging when they are dysfunctional as “shortevity genes.” So, also harkening back to earlier posts we have:
· WFS1 and CISD2 are shortevity genes associated with Wolfram Syndrome
· Certain of the sheltrin-producing genes are shortevity genes associated with Hoyeraal-Hreidarsson Syndrome(ref)
· WRN is a shortevity gene associated with Werner Syndrome(ref)
· LMNA is a shortevity gene associated with Hutchinson-Gilford progeria syndrome(ref)
Whether any of the shorevity genes have anything to do with possible extraordinary longevity is a very interesting open question.
