longevità

Sakiko Honjo

Young Life Scientist GE Prize 2010.

Assegnati i premi sponsorizzati da Science e sostenuti da GE Healthcare, l'azienda leader in prodotti di biologia moelcolare, e assegnati a Stoccolma il mese scorso, a 4 giovani ricercatori per l'Europa, (lo svizzero Ataman Sendoel per uno studio su proliferazione delle cellule, apoptosi e ipossia) Nord America (Mark Bates, studio su STochastic Optical Reconstruction Microscopy), Giappone  (Sakiko Honjo) e resto del mondo (Melissa Follwood, Singapore, già premio L'Oreal per le donne nella scienza, Genome-Wide Chromatin Loops Regulate Transcription).

"Is Aging Necessary?" 

 Nel suo studio sull'invecchiamento a sulla longevità, la Dr.ssa Honjo ha dimostrato una via di segnale più efficace di quella chiamata "restrizione calorica", ossia una dieta ferrea che simula la dieta nelle alimentazioni frugali delle comunità autosostenute.

• In the 1980s, a "longevity mutant" was discovered in the nematode Caenorhabditis elegans. The discovery that this mutant lives longer than the wild-type organism when the functioning of a certain gene is reduced means that the functioning of this gene shortens life span. The gene is known as the age-1 gene and encodes PI3K, a component in insulin-like signaling. It has also been discovered that life span is prolonged in Drosophila and rodents when insulin-like signaling is reduced.

Questa seconda via di segnale viene attivata attraverso il digiuno intermittente, ossia l'alternanza di  alimentazione a volontà e periodi di "scarsezza di cibo". 

La scoperta che in  nematodi il digiuno estende la longevità del 60%, è traferibile, nei meccanismi molecolari anche ai mammiferi ed all'uomo (presenza di proteine omologhe) e coinvolge un network proteico che va da Rheb (una proteina G, o GTPasi), insulina, FoxA passando per Target of Rapamycin (TOR).

• A. An image of worms cultured on an agar plate. A dotted circle indicates a region covered with E. coli, the standard laboratory food of worms (left). Schematic representations of dietary restriction regimens used in our study (right). B. Graphic summary of our study. Survival curves show that both of two dietary restriction regimens, intermittent fasting (red) and calorie restriction (light blue) extend worm’s life span. The evolutionarily conserved nutrient sensing pathway, Rheb/TOR pathway plays critical roles in both dietary restriction regimens.

• I  elucidated the role of evolutionarily conserved Rheb, a low molecular weight guanosine triphosphatase, in regulating life span. It was previously known that Rheb is activated by adenosine triphosphate (ATP) and amino acid nutrients. C. elegans’ life span is extended when Rheb expression is suppressed under conditions of abundant food. Thus, Rheb appears to promote aging under conditions of abundant nutrition. On the other hand, suppressing the expression of Rheb during intermittent fasting almost completely suppresses the life-span–extending effect of intermittent fasting. In other words, Rheb is essential for suppressing aging with intermittent fasting. These results suggest that the Rheb signal transmission pathway supports the two opposing functions of extending life span and restricting life span. Further genetic analysis revealed the presence of at least two pathways that regulate life span downstream from Rheb. One is the insulin-like signaling pathway, which functions to shorten life span, and the other is the pha-4 (FoxA C. elegans homolog) pathway, which functions to extend life span. Rheb appears to play the extremely important role of determining the ultimate aging rate and life span by regulating the balance of these multiple life-span–restricting pathways.