Key to aging immune system is discovered

by Jeffrey Norris
Key to aging immune system is discovered
Molecular tags of DNA damage are highlighted in green in blood-forming stem cells.

There's a good reason people over 60 are not donor candidates for bone marrow transplantation. The immune system ages and weakens with time, making the elderly prone to life-threatening infection and other maladies, and a UC San Francisco research team now has discovered a reason why.

"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 UCSF. Passegué, an expert on the that give rise to the blood and , led a team that published the new findings online July 30, 2014 in the journal Nature.

Blood and immune cells are short-lived, and unlike most tissues, must be constantly replenished. The cells that must keep producing them throughout a lifetime are called "." Through cycles of cell division these stem cells preserve their own numbers and generate the daughter cells that give rise to replacement blood and . But the hematopoietic stem cells falter with age, because they lose the ability to replicate their DNA accurately and efficiently during cell division, Passegué's lab team determined.

Especially vulnerable to the breakdown, the researchers discovered in their new study of old mice, are transplanted, aging, blood-forming stem cells, which lack the ability to make B cells of the immune system. These B cells make antibodies to help us fight all sorts of microbial infections, including bacteria that cause pneumonia, a leading killer of the elderly.

In old blood-forming stem cells, the researchers found a scarcity 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 allocated to daughter cells later in . 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" Passegué said.

But not all was well in the old, surviving stem cells. The molecular tags accumulated on genes needed to make the cellular factories known as ribosomes. The ribosomes make all the cell's proteins. Passegué will further explore the consequences of reduced protein production as part of her ongoing research.

"Everybody talks about healthier aging," Passegué 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."

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

More information: "Replication stress is a potent driver of functional decline in ageing haematopoietic stem cells." Johanna Flach, et al. Nature (2014) DOI: 10.1038/nature13619.

add to favorites email to friend print save as pdf

Related Stories

Opening-up the stem cell niche

Jul 11, 2014

For many years scientists have been trying to unravel mechanisms that guide function and differentiation of blood stem cells, those cells that generate all blood cells including our immune system. The study of human blood ...

Stem cells from nerves form teeth

Jul 29, 2014

Researchers at Karolinska Institutet in Sweden have discovered that stem cells inside the soft tissues of the tooth come from an unexpected source, namely nerves. These findings are now being published in the journal Nature and co ...

Recommended for you

Infant cooing, babbling linked to hearing ability

58 minutes ago

Infants' vocalizations throughout the first year follow a set of predictable steps from crying and cooing to forming syllables and first words. However, previous research had not addressed how the amount ...

Developing 'tissue chip' to screen neurological toxins

1 hour ago

A multidisciplinary team at the University of Wisconsin-Madison and the Morgridge Institute for Research is creating a faster, more affordable way to screen for neural toxins, helping flag chemicals that ...

Gene mutation discovered in blood disorder

5 hours ago

An international team of scientists has identified a gene mutation that causes aplastic anemia, a serious blood disorder in which the bone marrow fails to produce normal amounts of blood cells. Studying a family in which ...

Airway muscle-on-a-chip mimics asthma

8 hours ago

The majority of drugs used to treat asthma today are the same ones that were used 50 years ago. New drugs are urgently needed to treat this chronic respiratory disease, which causes nearly 25 million people ...

User comments

Adjust slider to filter visible comments by rank

Display comments: newest first

Scottingham
not rated yet Aug 04, 2014
So how long until I can freeze/store my supple 20-something stem cells for use later in life?