Sunday, May 22, 2011

Anti-aging research developments in rapamycin, sirtuins, and stem cells

The Third Bay Area Aging meeting was held at Berkeley on May 8, 2010.

One highlight was the emperor’s new clothes statement “Maybe C. Elegans (e.g.; worm) is not the correct model organism for human aging!

A variety of research was presented, with four themes amongst the most interesting:

1. Role of rapamycin in preventing inflammation
Rapamycin (more technically known as the mammalian target of rapamycin (mTOR)), has long been examined in aging since it is a protein that regulates a range of cellular behavior including growth, proliferation, motility, and survival. Initially hoped to be useful in treating cancer, rapamycin later turned out not to kill tumors due to systems biology; when mTOR is given and the TOR pathway is knocked out, the ERK pathway is upregulated instead.

However new research presented by Remi-Martin Laberge (Buck) shows that there is hope for rapamycin in the context of inflammation prevention. The normal process is that DNA damage response leads to NF-kB (a protein controlling DNA transcription) activation which leads to IL-6/8 (inflammation-related proteins) buildup, but with an mTOR introduction of rapamycin, instead IL-1a (an immune-response regulator) is obtained which prevents inflammation.

The prevention of inflammation is thought to be critical in anti-aging as many aging pathologies start with inflammation which later escalates to waste-build up and tissue break-down. This work is part of ongoing SASP (senescence-associated secretory phenotype) research by the Campisi lab (recent papers on p53 and p38MAPK).

2. Role of recently discovered SIRT7 in oncogenesis
Matt Barber (Stanford) presented work regarding a recently discovered SIRT (Silent Information Regulator) protein. SIRT7 is a chromatin-associated protein and site-specific histone H3 K18 deacetylase. There is a potential connection with SIRT7 and oncogenesis in that SIRT7 interacts with ELK4 (a pathway upregulated in cancer) to suppress a tumor suppressive gene expression network and helps stabilize aggressive cancer phenotypes.

3. Enhanced stem cell therapies
Randy Ashton (Berkeley) showed research regarding the increased ability to dopaminergiacally pattern hESCs to facilitate regenerative therapies for Parkinson’s disease. This was accomplished by making a protein important in neural development, sonic hedgehog, more sensitive through polyvalency.

4. Protein homeostasis and proteasome activity necessary for long lifespan
Brett Robison (Buck) presented work suggesting that normal proteasome function is required for full lifespan in yeast. The proteasome is an important location for waste degradation in cells. Aging cells showed impaired protein homeostasis and decreased proteasome function but it is unclear if this is cause or effect. Theodore Peters (Buck) also showed that maintaining protein homeostasis is important for healthy aging.

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