| |
 |
|
|
Science Forum Index » Life Extension Forum » Premature aging in mice activates a systemic metabolic...
Page 1 of 1
|
| Author |
Message |
| ... |
 Posted: Fri May 09, 2008 2:02 pm |
|
|
|
Guest
|
hmmmmmmm...............
Hum Mol Genet. 2008 Apr 28 [Epub ahead of print] Links
Premature aging in mice activates a systemic metabolic response
involving autophagy induction.Mariño G, Ugalde AP, Salvador-Montoliu
N, Varela I, Quirós PM, Cadiñanos J, van der Pluijm I, Freije JM,
López-Otín C.
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina,
Instituto Universitario de Oncología, Universidad de Oviedo, 33006-
Oviedo, Spain.
Autophagy is a highly regulated intracellular process involved in the
turnover of most cellular constituents and in the maintenance of
cellular homeostasis. It is well-established that the basal autophagic
activity of living cells decreases with age, thus contributing to the
accumulation of damaged macromolecules during aging. Conversely, the
activity of this catabolic pathway is required for lifespan extension
in animal models such as Caenorhabditis elegans and Drosophila
melanogaster. In this work, we describe the unexpected finding that
Zmpste24-null mice, which show accelerated aging and are a reliable
model of human Hutchinson-Gilford progeria, exhibit an extensive basal
activation of autophagy instead of the characteristic decline in this
process occurring during normal aging. We also show that this
autophagic increase is associated with a series of changes in lipid
and glucose metabolic pathways, which resemble those occurring in
diverse situations reported to prolong lifespan. These Zmpste24(-/-)
mice metabolic alterations are also linked to substantial changes in
circulating blood parameters, such as leptin, glucose, insulin or
adiponectin which in turn lead to peripheral LKB1-AMPK activation and
mTOR inhibition. On the basis of these results, we propose that
nuclear abnormalities causing premature aging in Zmpste24(-/-) mice
trigger a metabolic response involving the activation of autophagy.
However, the chronic activation of this catabolic pathway may turn an
originally intended pro-survival strategy into a pro-aging mechanism
and could contribute to the systemic degeneration and weakening
observed in these progeroid mice.
PMID: 18443001 [PubMed - as supplied by publisher] |
|
|
| Back to top |
|
| |
|
Page 1 of 1
All times are GMT - 5 Hours
The time now is Fri Dec 05, 2008 7:32 am
|
|