Yeast

The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms

The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to...

Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue

Caloric restriction has been shown to increase longevity in organisms ranging from yeast to mammals. In some organisms, this has been associated with a decreased fat mass and alterations in insulin/insulin-like growth factor 1 (IGF-1) pathw...

Mammalian sirtuins—emerging roles in physiology, aging, and calorie restriction

Sir2 is an NAD-dependent deacetylase that connects metabolism with longevity in yeast, worms and flies. Mammals contain seven homologs of yeast Sir2, SIRT1-7. Here, we review recent findings demonstrating the role of these mammalian sirtuin...

Handbook of the Biology of Aging

Lower Organisms: Identification of Longevity. Assurance Genes in Yeast. Molecular Genetic Approaches to Identifying Gerontogenes in Caenorhabditis Elegans. Genetic Approaches to Life Prolongation in Drosophila Melonogaster. Mutants Affectin...

Biodemographic Trajectories of Longevity

Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--conce...

Regulation of Longevity and Stress Resistance by Sch9 in Yeast

The protein kinase Akt/protein kinase B (PKB) is implicated in insulin signaling in mammals and functions in a pathway that regulates longevity and stress resistance in Caenorhabditis elegans. We screened for long-lived mutants in nondividi...

Nutrient sensing and TOR signaling in yeast and mammals

Selective autophagy of intracellular organelles: Recent research advances

Macroautophagy (hereafter called autophagy) is a highly conserved physiological process that degrades over-abundant or damaged organelles, large protein aggregates and invading pathogens via the lysosomal system (the vacuole in plants and y...

Molecular Determinants and Genetic Modifiers of Aggregation and Toxicity for the ALS Disease Protein FUS/TLS

TDP-43 and FUS are RNA-binding proteins that form cytoplasmic inclusions in some forms of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Moreover, mutations in TDP-43 and FUS are linked to ALS and FTLD. Ho...

Telomere-binding Protein TRF2 Binds to and Stimulates the Werner and Bloom Syndrome Helicases

Werner syndrome is a human premature aging disorder displaying cellular defects associated with telomere maintenance including genomic instability, premature senescence, and accelerated telomere erosion. The yeast homologue of the Werner pr...

The Hsp70/Hsp90 Chaperone Machinery in Neurodegenerative Diseases

TThe accumulation of misfolded proteins in the human brain is one of the critical features of many neurodegenerative diseases, including Alzheimer’s disease (AD). Assembles of beta-amyloid (Aβ) peptide – either soluble (oligomers - Aβ) or i...

Aging and Immortality: Quasi-Programmed Senescence and Its Pharmacologic Inhibition

While ruling out programmed aging, evolutionary theory predicts a quasi-program for aging, a continuation of the developmental program that is not turned off, is constantly on, becoming hyper-functional and damaging, causing diseases of agi...