recent aging discoveries a&s300-002 jim lund. regulation of yeast replicative life span by tor...
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![Page 1: Recent aging discoveries A&S300-002 Jim Lund. Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients. (Kaeberlein et al.,](https://reader035.vdocuments.us/reader035/viewer/2022062804/5697bf931a28abf838c8fc40/html5/thumbnails/1.jpg)
Recent aging discoveries
A&S300-002 Jim Lund
![Page 2: Recent aging discoveries A&S300-002 Jim Lund. Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients. (Kaeberlein et al.,](https://reader035.vdocuments.us/reader035/viewer/2022062804/5697bf931a28abf838c8fc40/html5/thumbnails/2.jpg)
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients. (Kaeberlein et al., 2005)
HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction.
(Lamming et al., 2005)
Yeast aging and CR
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Yeast aging and CR
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Wild type mice with short telomeres have germ cell
defects
HG heterozygote telomerase RNA mutants.WT wild type offspring of the hets.KO -/- knock-out offspring of the hets.
Hao et al., 2005
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Regulation of Lifespan in Drosophila by Modulation of Genes in the TOR Signaling Pathway.
(Kapahi et al., 2004)
TOR=Target Of Rapamycin
(rapamycin is a product of the bacterium Streptomyces hygroscopicus found in a soil sample from the island Rapa Nui, better known as Easter Island!)
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Mutations in fly TOR extend lifespan
![Page 7: Recent aging discoveries A&S300-002 Jim Lund. Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients. (Kaeberlein et al.,](https://reader035.vdocuments.us/reader035/viewer/2022062804/5697bf931a28abf838c8fc40/html5/thumbnails/7.jpg)
A Conserved MST-FOXO Signaling Pathway Mediates Oxidative-Stress Responses and Extends Life Span
•Protein kinases in the Ste20(yeast)/MST (mammals)/hippo(flies)/CST(worms) regulate cellular responses to oxidative stress.
•FOXO3(mammals)/daf-16(worms) is activated by the MST kinases in response to oxidative stress.
(Lehtinen et al., 2006)
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Overexpression of cst-1 in worms extends lifespan
cst-1 overexpression
cst-1 is a STET-20-like kinase (a signaling pathway gene)-This is the first study on cst-1, nothing else is known about it.
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MST/cst-1 signals (in part) through FOXO/daf-16
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Caenorhabditis elegans HCF-1 Functions in Longevity Maintenance as a DAF-16 RegulatorJi Li, Atsushi Ebata, Yuqing Dong,¤ Gizem Rizki, Terri Iwata, and Siu Sylvia Lee (Cornell Univ)
hcf-1 worms are long-lived.HCF-1 is nuclear localized and physically associated with DAF-16, and prevents DAF-16 from binding to promoters of genes.
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Growing evidence of the role of inflammation in aging
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Transgenic Mice with a Reduced Core Body Temperature Have an Increased
Life Span
Expressed uncoupling protein UCP2 in the lateral hypothalamus.
(Conti et al., 2006)
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Reduced body temperature extends lifespan in mice
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Resveratrol improves health and survival of mice on a high-calorie diet
(Baur et al., 2006)
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Organ pathology improved on resveratrol
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Discoveries in the insulin-like signaling pathway
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SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging.Oberdoerffer et al., 2008 (Sinclair lab)
A. Survival of irradiated p53+/ mice fed normal or resveratrol-supplemented chow.
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SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging.Oberdoerffer et al., 2008 (Sinclair lab)
D. q-RT-PCR analysis of SIRT1-bound genes (left) and non-SIRT1-bound genes (right) including housekeeping genes (rps16, hprt) and genes upregulated in 30-month-old mice by microarray.
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High cognitive function elderly have low tangle levels
Resistant to tangle formationTangles main component is tau protein.
Changiz Geula (Northwestern University)
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