Apr. 15, 2011 Eight genes which control levels of the main steroid produced by the adrenal gland, believed to play a role in aging and longevity, have been uncovered by an international consortium of scientists, co-led by King's College London.
Crucially, some of these eight genetic regions are also associated with important diseases of aging, including type 2 diabetes and lymphoma. Researchers say that these findings, published in the journal PLoS Genetics on April 14, provide the first genetic evidence for the aging role of the steroid, and therefore highlights it as a marker of biological aging.
It was already known that the concentration of the steroid dehydroepiandrosterone sulphate (DHEAS), declines rapidly with age -- it diminishes by 95 per cent by the age of 85. This has led to speculation that a relative DHEAS deficiency may contribute to common age-related diseases or diminished longevity.
To explore the mechanisms behind declining levels of the steroid, the researchers carried out an analysis of DHEAS levels and 2.5 million genetic variants in 14,846 people from Europe and USA. They found eight common genes that control the blood concentration of DHEAS, and importantly some of these genes are associated with aging and common age-related diseases such as type 2 diabetes and lymphoma.
Lead author, Dr Guangju Zhai from King's College London, said: 'This is the first large-scale study to unlock the mystery that has always surrounded DHEAS. We have identified specific genes that control its concentration levels, and shown that some of these are also involved in the aging process and age-related diseases.
'The findings provide us with the basis for future studies to look into potential mechanisms of exactly how the DHEAS is involved in aging. The next important question to try and answer is whether sustained high levels of DHEAS can in fact delay the aging process and prevent age-related diseases.'
'Professor Tim Spector, senior co-author from King's, said: 'This study shows the power of collaborative genetic studies to uncover mechanisms of how the body works. For 50 years we have observed the most abundant circulating steroid in the body, DHEAS, with no clue as to its role. Now its genes have shown us its importance in many parts of the aging process.'
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- Guangju Zhai, Alexander Teumer, Lisette Stolk, John R. B. Perry, Liesbeth Vandenput, Andrea D. Coviello, Annemarie Koster, Jordana T. Bell, Shalender Bhasin, Joel Eriksson, Anna Eriksson, Florian Ernst, Luigi Ferrucci, Timothy M. Frayling, Daniel Glass, Elin Grundberg, Robin Haring, Åsa K. Hedman, Albert Hofman, Douglas P. Kiel, Heyo K. Kroemer, Yongmei Liu, Kathryn L. Lunetta, Marcello Maggio, Mattias Lorentzon, Massimo Mangino, David Melzer, Iva Miljkovic, Alexandra Nica, Brenda W. J. H. Penninx, Ramachandran S. Vasan, Fernando Rivadeneira, Kerrin S. Small, Nicole Soranzo, André G. Uitterlinden, Henry Völzke, Scott G. Wilson, Li Xi, Wei Vivian Zhuang, Tamara B. Harris, Joanne M. Murabito, Claes Ohlsson, Anna Murray, Frank H. de Jong, Tim D. Spector, Henri Wallaschofski. Eight Common Genetic Variants Associated with Serum DHEAS Levels Suggest a Key Role in Ageing Mechanisms. PLoS Genetics, 2011; 7 (4): e1002025 DOI: 10.1371/journal.pgen.1002025
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