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SUMMARY:The role of mitochondria in health and disease
DTSTART:20150504T133000
DTEND:20150504T143000
DTSTAMP:20260916T220423Z
UID:3b066baab2bbf9c12e9ba79b19906e6b47d0f5dc0a69e187a19c9a2e
CATEGORIES:Conferences - Seminars
DESCRIPTION:Riekelt Houtkooper - Academic Medical Center (AMC)\, Amsterdam
 \, Netherlands\nAging is a complex process that is coordinated by overlapp
 ing and partially independent processes often involving changes in metabol
 ic networks. Anabolic caloric excess pathways—such as those involving in
 sulin/IGF1 and mTOR—decrease lifespan\, whereas the catabolic caloric re
 striction pathways—for instance those involving AMPK and sirtuin—incre
 ase lifespan. We used a genetic cross of mice (the BXD lines) and quantita
 tive trait locus mapping to identify mitochondrial ribosomal protein S5 (M
 rps5)\, and other members of the mitochondrial ribosomal protein (MRP) fam
 ily as candidate metabolic and longevity regulators. A 50% variation in na
 tural expression corresponds to approximately 250 days difference in lifes
 pan. Using loss-of-function experiments in C. elegans\, we validated the r
 ole of homologous MRPs in longevity via mechanisms that trigger a reductio
 n in mitochondrial respiration and activation of the mitochondrial unfolde
 d protein response (UPRmt). Importantly\, the level of UPRmt activation co
 rrelated directly with lifespan extension. These effects were further conf
 irmed by treatment with specific antibiotics that target bacterial and mit
 ochondrial protein translation—for instance doxycycline and chlorampheni
 col. Despite the beneficial effects of antibiotics on lifespan\, we also o
 bserved that the worms developed more slowly and stayed small. We demonstr
 ated that these adverse effects are not restricted to worms\, but also app
 ly to commonly used cell lines\, flies\, mice\, and plants. Collectively\,
  these data expose the MRP proteins as a treatment target against age-rela
 ted disease\, but also call for caution with respect to antibiotic use in 
 experimental systems (Tet-on/Tet-off) and the environment\, for instance i
 n livestock.
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STATUS:CONFIRMED
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