Till sidans topp

Sidansvarig: Webbredaktion
Sidan uppdaterades: 2012-09-11 15:12

Tipsa en vän

Premature ageing in mice … - Göteborgs universitet Till startsida
Till innehåll Läs mer om hur kakor används på gu.se

Premature ageing in mice expressing defective mitochondrial DNA polymerase

Artikel i vetenskaplig tidskrift
Författare A. Trifunovic
A. Wredenberg
Maria Falkenberg
J. N. Spelbrink
A. T. Rovio
C. E. Bruder
Mohammad Bohlooly-Yeganeh
S. Gidlof
Anders Oldfors
R. Wibom
J. Tornell
H. T. Jacobs
N. G. Larsson
Publicerad i Nature
Volym 429
Nummer/häfte 6990
Sidor 417-4 23
ISSN 0028-0836
Publiceringsår 2004
Publicerad vid
Sidor 417-4 23
Språk en
Ämneskategorier Medicin och Hälsovetenskap


Point mutations and deletions of mitochondrial DNA (mtDNA) accumulate in a variety of tissues during ageing in humans, monkeys and rodents. These mutations are unevenly distributed and can accumulate clonally in certain cells, causing a mosaic pattern of respiratory chain deficiency in tissues such as heart, skeletal muscle and brain. In terms of the ageing process, their possible causative effects have been intensely debated because of their low abundance and purely correlative connection with ageing. We have now addressed this question experimentally by creating homozygous knock-in mice that express a proof-reading-deficient version of PolgA, the nucleus-encoded catalytic subunit of mtDNA polymerase. Here we show that the knock-in mice develop an mtDNA mutator phenotype with a threefold to fivefold increase in the levels of point mutations, as well as increased amounts of deleted mtDNA. This increase in somatic mtDNA mutations is associated with reduced lifespan and premature onset of ageing-related phenotypes such as weight loss, reduced subcutaneous fat, alopecia (hair loss), kyphosis (curvature of the spine), osteoporosis, anaemia, reduced fertility and heart enlargement. Our results thus provide a causative link between mtDNA mutations and ageing phenotypes in mammals.

Sidansvarig: Webbredaktion|Sidan uppdaterades: 2012-09-11

På Göteborgs universitet använder vi kakor (cookies) för att webbplatsen ska fungera på ett bra sätt för dig. Genom att surfa vidare godkänner du att vi använder kakor.  Vad är kakor?