MedicalResearch.com Interview with:
Jerry W. Shay PhD
Department of Cell Biology,
UT Southwestern Medical Center
MedicalResearch.com: What did you find?
Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population.
MedicalResearch.com: Why is it important?
Response: Previously it was thought aging was caused by a DNA damage signal from a too short telomere. This work demonstrates that certain aspects of normal human aging can be regulated by progressively shortened telomeres not requiring a DNA damage signal. This has great value in understanding how we measure changes over decades. The progressively telomere shortening is a counting mechanism and we believe at various stages of human aging that different genes become activated or silenced via this mechanism.
MedicalResearch.com: What are the implications of your findings for the disease(s)?
Response: There are certain telomere genetic diseases where patients such as idiopathic pulmonary fibrosis are born with greatly shortened telomeres limiting stem cell renewal. Some of these patients are diagnosed before disease onset. It is possible in the future that we might transiently elongate telomeres in the lung and prevent disease progression or increase the time until disease onset.
MedicalResearch.com: How does/will this help patients?
Response: Our studies show that preventing telomeres from becoming too short may prevent or delay diseases such as pulmonary fibrosis, dyskeratosis congenita, and cancer.
MedicalResearch.com: How does/will this help other researchers/physicians in the field?
Response: This study opens up the possibility to treat certain patients where today there are no treatments.
MedicalResearch.com: What cautions should be considered in interpreting the results?
Response: These studies were done in cells outside the body (in cell culture) so extrapolation to humans is uncertain at present.
MedicalResearch.com: Does this build on earlier research? If so, please explain.
Response: We term the findings in this study, telomere position effect over long distance (or TPE-OLD). We previously found a gene that is involved in a type of muscular dystrophy, FSHD, that is also regulated by TPE.
Nature, Structural and Molecular Biology, 20 (6): 671-678, 2013.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Regulation of the Human Telomerase Gene TERT by Telomere Position Effect—Over Long Distances (TPE-OLD): Implications for Aging and Cancer
Wanil Kim ,Andrew T. Ludlow ,Jaewon Min,Jerome D. Robin,Guido Stadler,Ilgen Mender,Tsung-Po Lai,Ning Zhang,Woodring E. Wright,Jerry W. Shay
PLOS Biology Published: December 15, 2016
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