Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
PZ HTL SA

DNA Replication Difficulty May Be Key to Immune System Aging

By BiotechDaily International staff writers
Posted on 13 Aug 2014
Image: Molecular tags of DNA damage are highlighted in green in blood-forming stem cells (Photo courtesy of UCSF – University of California, San Francicsco).
Image: Molecular tags of DNA damage are highlighted in green in blood-forming stem cells (Photo courtesy of UCSF – University of California, San Francicsco).
People over 60 are not donor candidates for bone marrow transplantation; the immune system ages and weakens with time, making the elderly predisposed to life-threatening infection and other disorders. US researchers have now have found a reason.

“We have found the cellular mechanism responsible for the inability of blood-forming cells to maintain blood production over time in an old organism, and have identified molecular defects that could be restored for rejuvenation therapies,” said Emmanuelle Passegué, PhD, a professor of medicine and a member of the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research at the University of California, San Francisco (UCSF; USA). Dr. Passegué, a stem cell specialist, led a team that published their findings online July 30, 2014 in the journal Nature.

Blood and immune cells no not live long, and not like most tissues, must be continually replenished. The cells that must keep generating them throughout a lifetime are called hematopoietic stem cells. Through cycles of cell division these stem cells preserve their own numbers and generate the daughter cells that replenish replacement blood and immune cells. But the hematopoietic stem cells falter with age, because they lose the ability to replicate their DNA accurately and efficiently during cell division, Dr. Passegué’s lab team determined.

Particularly susceptible to the degradation, the researchers discovered in their new study of older mice, are transplanted, aging, blood-forming stem cells, which no not have the ability to produce B cells of the immune system. These B cells generate antibodies to help treat many types of microbial infections, including bacteria that cause pneumonia, a leading killer of the older people.

In old blood-forming stem cells, the researchers found a lack of specific protein components needed to form a molecular machine called the mini-chromosome maintenance helicase, which unwinds double-stranded DNA so that the cell’s genetic material can be duplicated and assigned to daughter cells later in cell division. In their study, the stem cells were stressed by the loss of activity of this machine, and as a result, were at heightened risk for DNA damage and death when forced to divide.

The researchers discovered that even after the stress associated with DNA replication, surviving, non-dividing, resting, old stem cells retained molecular tags on DNA-wrapping histone proteins, a feature often associated with DNA damage. However, the researchers determined that these old survivors could repair induced DNA damage as efficiently as young stem cells. “Old stem cells are not just sitting there with damaged DNA ready to develop cancer, as it has long been postulated,” Dr. Passegué said.

The older surviving stem cells still had problems. The molecular tags accumulated on genes required to generate the cellular factories known as ribosomes. Dr. Passegué will further examine the concerns of reduced protein production as part of her ongoing research. “Everybody talks about healthier aging,” he added. “The decline of stem-cell function is a big part of age-related problems. Achieving longer lives relies in part on achieving a better understanding of why stem cells are not able to maintain optimal functioning.”

Dr. Passegué hopes that it might be possible to prevent declining stem-cell populations by developing a medicine to prevent the loss of the helicase components required to effectively unwind and replicate DNA, thereby avoiding immune-system failure.

Related Links:

University of California, San Francisco



comments powered by Disqus

Channels

Drug Discovery

view channel
Image: The nano-cocoon drug delivery system is biocompatible, specifically targets cancer cells, can carry a large drug load, and releases the drugs very quickly once inside the cancer cell. Ligands on the surface of the \"cocoon\" trick cancer cells into consuming it. Enzymes (the “worms\" in this image) inside the cocoon are unleashed once inside the cell, destroying the cocoon and releasing anticancer drugs into the cell (Photo courtesy of Dr. Zhen Gu, North Carolina State University).

Novel Anticancer Drug Delivery System Utilizes DNA-Based Nanocapsules

A novel DNA-based drug delivery system minimizes damage to normal tissues by utilizing the acidic microenvironment inside cancer cells to trigger the directed release of the anticancer drug doxorubicin (DOX).... Read more

Lab Technologies

view channel

Experimental Physicists Find Clues into How Radiotherapy Kills Cancer Cells

A new discovery in experimental physics has implications for a better determination of the process in which radiotherapy destroys cancer cells. Dr. Jason Greenwood from Queen’s University Belfast (Ireland) Center for Plasma Physics collaborated with scientists from Italy and Spain on the work on electrons, and published... Read more

Business

view channel

Interest in Commercial Applications for Proteomics Continues to Grow

Increasing interest in the field of proteomics has led to a series of agreements between private proteomic companies and academic institutions as well as deals between pharmaceutical companies and novel proteomics innovator biotech companies. Proteomics is the study of the structure and function of proteins.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.