HKU Bulletin April 2006 (Vol. 7 No. 2)

7 T he fantasy may have always been beyond reach but scientists believe they are now closer than ever to unlocking the secrets of ageing. Recent studies have suggested that ageing can be regulated under certain environmental conditions, such as extreme calorie restriction or through genetic manipulation. And biochemists at the University are hoping that by studying the connection between two age-controlling genes they can uncover the mystery of what makes us grow old. Associate Professor Zhou Zhongjun, of the Department of Biochemistry, said he and his team are collaborating with scientists from the University of Washington to uncover the connection between SIR2 and Lamin A. The SIR2 gene is an important factor in metabolism and is known to be involved in the normal ageing process. Scientists have been aware, for several years, that adding an extra copy of SIR2 can promote longevity in yeast, worms and fruit flies. But, a counterproductive experiment by scientists at the University of Southern California, last year, in which SIR2 was deleted completely, resulted in the longest lifespan ever recorded in any organism — up to six times the normal lifespan of yeast, worms and fruit flies. The Lamin A gene, on the other hand, is known to cause devastating effects on cellular structure and function in children wi th Hutchinson-Gi l ford Proger ia Syndrome, a condi t ion characterized by accelerated ageing. Zhou and his team are testing Sirt1, the human homologue of yeast ageing genes SIR2 to discover its role in regulating other genes. He said: “The ageing process is very complex but there is a link between the factors that cause it. We are trying to understand the link between SIR2 and Lamin A. We’re trying to discover the connection between these two pathways to see if it leads to an abnormal or accelerated ageing process. “At the moment, because we are still in the process of trying to understand the link we can’t draw any conclusions. We are investigating how mutations in Lamin A affect the Sirt1-mediated ageing process and whether there are common downstream targets that regulate the normal and abnormal ageing processes.” He said the ultimate goal of the research was to understand how normal people age. “We do that by studying how people age abnormally because the models for normal ageing are not very good. If we can find out what causes accelerated ageing then we will have a clearer idea of what happens in the normal ageing process.” Unlocking the Secrets of Ageing 6 COVER STORY