Molecular studies of longevity-associated genes in yeast and mammalian cells

Aging is a complex process affecting diverse organisms from bacteria to humans. Despite strong evolutionary arguments against the conservation of a single mechanism of aging, a variety of conserved single gene mutations have been found to extend life span and stave off aging in several different species. The study of these mutations yields important insights into the biology of aging. In Saccharomyces cerevisiae, aging can be studied by mutations that extend the replicative potential of mother cells. With successive cell divisions, instability at the rDNA locus and extrachromosomal rDNA circle accumulation exponentially increase the likelihood of senescence and mortality. Aging can be forestalled by caloric restriction, a regimen that increases the activity of Sir2p, an NAD-dependent protein deacetylase and important regulator of aging in yeast and some metazoans. Caloric restriction activates respiration, reducing cellular NADH levels and relieving the competitive inhibition of Sir2p by this metabolite. SSD1 promotes longevity by a Sir2p-independent mechanism that affects neither ERC formation nor rDNA silencing. Ssd1p directly represses the translation of the mitochondrial and cell wall glycoprotein Uthl.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2006

Author dc:creator

• Liszt, Gregory (Gregory Birjandi)

Advisor dc:contributor.advisor

• Leonard Guarente.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/34189
• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Identifier URI

http://dspace.mit.edu/handle/1721.1/34189

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/34189