The Biogerontology Research Foundation
Mammals must finely balance stimulation and suppression of cell division: over-permissive cellular proliferation promotes cancer, whereas over-restrictive cell division promotes degeneration. This is especially true in tissues with a high cell turnover, such as the blood. Genetic manipulation of the machinery that maintains the ends of our chromosomes, combined with cell therapy, is potentially a very powerful way to alleviate this problem. However, such an approach is highly complex; as a result, researchers have been reluctant to investigate its components. In this new project, the blood will be used as an example to demonstrate the feasibility of such a manipulation.
Recent data suggest that impaired function of adult stem cells could contribute to the ageing process and decline of organ maintenance and function and there is mounting evidence that accumulation of DNA damage can limit stem cell function by triggering stem cell intrinsic checkpoints. Telomere shortening represents a cell intrinsic mechanism that leads to an accumulation of DNA damage in ageing cells. First noted as a mitotic clock for cellular ageing, telomere shortening has now been documented in most organs and tissues of ageing humans.
“This project will be the first ever test of whether intrinsically mortal stem cells can maintain a proliferating tissue indefinitely if periodically replenished. If the answer is yes, this will motivate exploring such treatments as part of an exceptionally robust cancer-prevention therapy", said Aubrey de Grey, Chief Scientific Officer of the SENS Foundation, an American charity that works to develop new therapies to treat diseases of the elderly.
Previous experimental evidence in late generation telomerase knockout mice indicates that telomere dysfunction limits the hematopoietic stem cell (HSC) function and maintenance during ageing. To test the hypothesis that transplanting HSC with long telomeres can improve survival and organ homeostasis, the BGRF and the IBA will support the work of the international research team led by Zhenyu Ju, MD, PhD* together with Leonard Rudolph, MD**. Over the three year period the group will conduct series of experiments transplanting the HSCs from the wild-type mice into telomere dysfunctional mice.
In addition, the research team will also investigate whether telomerase has a role in HSC function independent of its role in regulating telomere length. The group will test whether HSCs from the early- generation telomerase knockout mice can repopulate and rescue the ageing of hematopoietic system in late-generation telomerase knockout mice.
* Zhenyu Ju, M.D. and Ph.D., Principal Investigator, Max-Planck-Partner-
** K. Lenhard Rudolph, M.D., Chairman, Department of Molecular Medicine and Max-Planck-Research Group on Stem Cell Aging, Ulm, Germany
About the Biogerontology Research Foundation:
The Biogerontology Research Foundation is a registered UK charity # 1124054. The BGRF seeks to fill a gap within the research community, whereby the current scientific understanding of the ageing process is not yet being sufficiently exploited to produce effective medical interventions. The BGRF will fund research which, building on the body of knowledge about how ageing happens, will develop biotechnological interventions to remediate the molecular and cellular deficits which accumulate with age and which underlie the ill-health of old age. Addressing ageing damage at this most fundamental level will provide an important opportunity to produce effective treatments for the diseases of ageing. The goal is to improve quality of life in the elderly. The BGRF seeks to use modern biotechnology to attack the changes that take place in ageing, and to address the fundamental mechanisms of those diseases.
About the Institute of Biology of Aging:
The IBA is a non-profit research organization established to identify, stimulate and support aging research. The IBA has supported research projects in China, Germany, Russia, UK and US. The organization offers research fellowships to outstanding scientists at top academic institutions and helps academic investigators and prospective start up companies acquire initial capital to commercialize aging research.
