Engineered yeast set a record in longevity. What are the implications for humans?

Restrict nutrient access, remove a couple of genes and one lives 5-fold longer than normal. This is not science fiction, this is the cutting edge science. But, of course, I am not talking about humans here. The research was done on a unicellular organism, yeast. In the paper published this month in Cell the authors state that they have created conditions that “causes one of the longest chronological lifespan extensions reported for any organism”.

Interestingly, the gene, called Sir2, that the scientists have removed to create the record longevity in yeast, is the same gene that was previously shown to extend longevity if its activity is INCREASED! Yes, Sir2, when overactivated, has been known to cause a longer life span in different organisms, from yeast to flies. How to reconcile these two opposite observations? It appears that Sir2 can play different roles in different cells. In the cells that are actively dividing extra Sir2 activity extends their capacity to divide. While in the cells that have stopped dividing, extra Sir2 activity appears to be harmful.

If Sir2 can have two opposite effects on life span depending on the cell state, which of the roles could be critical for human longevity? The most likely answer is “both”. Human body is made of billions of cells. Some of them are capable of dividing, the others are not, but we need them both. Therefore, provided that the human Sir2 similarly has dual function like its counterpart from yeast, simply turning Sir2 on or off may not be enough to extend our life span. If too much Sir2 is not good for dividing cells, while too little is not good for the post-mitotic ones, could it be that we have just the right amount?

Cell. 2005 Nov 18;123(4):655-67.
Sir2 blocks extreme life-span extension.

Fabrizio P, Gattazzo C, Battistella L, Wei M, Cheng C, McGrew K, Longo VD.Andrus Gerontology Center and Department of Biological Sciences, University of Southern California, 3715 McClintock Avenue, Los Angeles, California 90089.

Sir2 is a conserved deacetylase that modulates life span in yeast, worms, and flies and stress response in mammals. In yeast, Sir2 is required for maintaining replicative life span, and increasing Sir2 dosage can delay replicative aging. We address the role of Sir2 in regulating chronological life span in yeast. Lack of Sir2 along with calorie restriction and/or mutations in the yeast AKT homolog, Sch9, or Ras pathways causes a dramatic chronological life-span extension. Inactivation of Sir2 causes uptake and catabolism of ethanol and upregulation of many stress-resistance and sporulation genes. These changes while sufficient to extend chronological life span in wild-type yeast require severe calorie restriction or additional mutations to extend life span of sir2Delta mutants. Our results demonstrate that effects of SIR2 on chronological life span are opposite to replicatve life span and suggest that the relevant activities of Sir2-like deacetylases may also be complex in higher eukaryotes.

Time Magazine: Cloned Dog – the most amazing invention of 2005. Is the world running low on inventions?

Or is Time Magazine running low on brain power?

“NEW YORK (Reuters) - Snuppy, the first cloned dog, is the most amazing invention of 2005, Time magazine said on Sunday.” Surely, this cute little puppy makes a wonderful cover. But is it the most amazing invention of 2005? Really?

I understand why many would consider cloning of the first large mammal Dolly the sheep in 1997 as an important invention. But during the last 8 years we have seen much progress in the area of cloning. Many large mammals have been cloned since then: cows, pigs, rabbits, horses, and even such valuable pet as cat. These days anything but cloning human being can’t really be considered a huge break-through. So, where does the importance of dog cloning come from? Are dogs more important pets than cats? Or is it simply because a cute puppy picture is so more valuable to Time Magazine than anything more substantive?

Voluntary disclaimer: Health Filbert does not own any dogs or cats.

11/13/05 by Health Filbert

Herceptin may not be the "cure" for breast cancer

The Lancet questions if herceptin is indeed the "cure" for breast cancer: << ...As Victor Montori and colleagues advised in last week's JAMA, such analyses may “show implausibly large treatment effects”. They recommend that “clinicians should view the results of such trials with scepticism”. The two NEJM reports use different dosing regimens, making comparisons and conclusions additionally more difficult. It is especially hard to tease apart the results because one of the papers combines results from two trials sponsored by Genentech. Although the “joint analysis was developed and analysed” by both trial teams, it is not made clear whether this synthesis was planned in advance of the start of both trials...>>

Also not enough evidence has been presented in Lancet Editor's opinion about cardiovascular side effects: <<...Comparisons are further hampered by the omission of crucial overall and disease-free survival data, as well as information on cardiotoxicity. However, it is clear that Herceptin can precipitate severe heart failure in some patients. The best that can be said about Herceptin's efficacy and safety for the treatment of early breast cancer is that the available evidence is insufficient to make reliable judgments...>>
(The Lancet 2005; 366:1673 DOI:10.1016/S0140-6736(05)67670-2)