Aging and nuclear organization: lamins and progeria.
The discoveries of at least eight human diseases arising from mutations in LMNA, which encodes the nuclear A-type lamins, have revealed the nuclear envelope as an organelle associated with a variety of fundamental cellular processes. The most recently discovered diseases associated with LMNA mutations are the premature aging disorders Hutchinson-Gilford progeria syndrome (HGPS) and atypical Werner's syndrome. The phenotypes of both HGPS patients and a mouse model of progeria suggest diverse compromised tissue functions leading to defects reminiscent of aging. Aspects of the diseases associated with disrupted nuclear envelope/lamin functions may be explained by decreased cellular proliferation, loss of tissue repair capability and a decline in the ability to maintain a differentiated state.
Mounkes
Leslie C
LC
Cancer and Developmental Biology Laboratory, National Cancer Institute at Frederick, National Institutes of Health, PO Box B, Frederick, Maryland 21702, USA.
Stewart
Colin L
CL
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D034882:Lamins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism; D011371:Progeria / Q000378:metabolism* / Q000473:pathology; D014898:Werner Syndrome / Q000378:metabolism* / Q000473:pathology
D034882:Lamins