Sirtuin 2

Publication Title: 
The EMBO journal

The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation.

Author(s): 
Langley, Emma
Pearson, Mark
Faretta, Mario
Bauer, Uta-Maria
Frye, Roy A.
Minucci, Saverio
Pelicci, Pier Giuseppe
Kouzarides, Tony
Publication Title: 
Bioscience, Biotechnology, and Biochemistry

The anti-aging effects of phloridzin on the yeast Saccharomyces cerevisiae were investigated by employing a replicative lifespan assay of the K6001 yeast strain. After administrating phloridzin at doses of 3, 10, and 30 µM, the lifespan of the yeast was significantly prolonged in comparison with the untreated group (p<0.01, p<0.001). To determine the mechanism of action, anti-oxidative experiments and ROS assay were performed.

Author(s): 
Xiang, Lan
Sun, Kaiyue
Lu, Jun
Weng, Yufang
Taoka, Akiko
Sakagami, Youji
Qi, Jianhua
Publication Title: 
PLoS genetics

Aging is characterized by the accumulation of damaged cellular macromolecules caused by declining repair and elimination pathways. An integral component employed by cells to counter toxic protein aggregates is the conserved ubiquitin/proteasome system (UPS). Previous studies have described an age-dependent decline of proteasomal function and increased longevity correlates with sustained proteasome capacity in centenarians and in naked mole rats, a long-lived rodent. Proof for a direct impact of enhanced proteasome function on longevity, however, is still lacking.

Author(s): 
Kruegel, Undine
Robison, Brett
Dange, Thomas
Kahlert, G¸nther
Delaney, Joe R.
Kotireddy, Soumya
Tsuchiya, Mitsuhiro
Tsuchiyama, Scott
Murakami, Christopher J.
Schleit, Jennifer
Sutphin, George
Carr, Daniel
Tar, Krisztina
Dittmar, Gunnar
Kaeberlein, Matt
Kennedy, Brian K.
Schmidt, Marion
Publication Title: 
EMBO molecular medicine

Sirtuins are NAD-dependent protein deacetylases known to have protective effects against age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7), which display diversity in subcellular localization and function. While SIRT1 has been extensively investigated due to its initial connection with lifespan extension and involvement in calorie restriction, important biological and therapeutic roles of other sirtuins have only recently been recognized.

Author(s): 
Donmez, Gizem
Outeiro, Tiago F.
Publication Title: 
Nature Reviews. Genetics
Author(s): 
Alfred, J.
Publication Title: 
Mechanisms of Ageing and Development

The phenomenon that caloric restriction increases life span in a variety of species from yeast to mice has been the focus of much interest. Recent observations suggest that a protein important for heterochromatin formation, Sir2, is central for caloric restriction-induced longevity in lower organisms.

Author(s): 
Hasty, P.
Publication Title: 
Nature
Author(s): 
Lee, Siu Sylvia
Ruvkun, Gary
Publication Title: 
Science (New York, N.Y.)
Author(s): 
Strauss, Evelyn
Publication Title: 
Nature

In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases. Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan, and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor.

Author(s): 
Howitz, Konrad T.
Bitterman, Kevin J.
Cohen, Haim Y.
Lamming, Dudley W.
Lavu, Siva
Wood, Jason G.
Zipkin, Robert E.
Chung, Phuong
Kisielewski, Anne
Zhang, Li-Li
Scherer, Brandy
Sinclair, David A.
Publication Title: 
Science (New York, N.Y.)
Author(s): 
Hall, Stephen S.

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