Progeria of stem cells: stem cell exhaustion in Hutchinson-Gilford progeria syndrome.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal genetic disorder that is characterized by segmental accelerated aging. The major causal mutation associated with HGPS triggers abnormal messenger RNA splicing of the lamin A gene leading to changes in the nuclear architecture. To date, two models have been proposed to explain how mutations in the lamin A gene could lead to HGPS, structural fragility and altered gene expression. We favor a compatible model that links HGPS to stem cell-driven tissue regeneration. In this model, nuclear fragility of lamin A-deficient cells increases apoptotic cell death to levels that exhaust tissues' ability for stem cell-driven regeneration. Tissue-specific differences in cell death or regenerative potential, or both, result in the tissue-specific segmental aging pattern seen in HGPS. We propose that the pattern of aging-related conditions present or absent in HGPS can provide insight into the genetic and environmental factors that contribute to normal aging.
Halaschek-Wiener
Julius
J
Canada's Michael Smith Genome Sciences Centre, BC Cancer Agency, BC Cnacer Research centre, Vancouver, Canada. juliushw@bcgsc.ca
Brooks-Wilson
Angela
A
D000375:Aging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006801:Humans; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011371:Progeria / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D012038:Regeneration; D013234:Stem Cells / Q000502:physiology*
D034904:Lamin Type A; D012333:RNA, Messenger