title: Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches.
abstract: Adult stem cells have been identified in most mammalian tissues of the adult body and are known to support the continuous repair and regeneration of tissues. A generalized decline in tissue regenerative responses associated with age is believed to result from a depletion and/or a loss of function of adult stem cells, which itself may be a driving cause of many age-related disease pathologies. Here we review the striking similarities between tissue phenotypes seen in many degenerative conditions associated with old age and those reported in age-related nuclear envelope disorders caused by mutations in the LMNA gene. The concept is beginning to emerge that nuclear filament proteins, A-type lamins, may act as signalling receptors in the nucleus required for receiving and/or transducing upstream cytosolic signals in a number of pathways central to adult stem cell maintenance as well as adaptive responses to stress. We propose that during ageing and in diseases caused by lamin A mutations, dysfunction of the A-type lamin stress-resistant signalling network in adult stem cells, their progenitors and/or stem cell niches leads to a loss of protection against growth-related stress. This in turn triggers an inappropriate activation or a complete failure of self-renewal pathways with the consequent initiation of stress-induced senescence. As such, A-type lamins should be regarded as intrinsic modulators of ageing within adult stem cells and their niches that are essential for survival to old age.
authors.affiliation: School of Biological and Biomedical Science, Integrated Cell Biology Laboratories, Durham University, South Road, Durham DH1 3LE, UK. vanja.pekovic@durham.ac.uk
authors.forename: Vanja
authors.initials: V
authors.lastname: Pekovic
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hutchison
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000502:physiology*; D000368:Aged; D016922:Cellular Senescence / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D034904:Lamin Type A / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D034904:Lamin Type A