August 01, 2014
Clue On Immune System Aging

Why do old folks die from influenza and other infectious diseases? Aged immune systems. Some UCSF researchers have a clue as to why: diminished function of protein helicase that helps cells replicate.

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 stem cells that give rise to the blood and immune system, led a team that published the new findings online July 30, 2014 in the journal Nature.

We need youthful stem cell therapies that can replace our aging immune systems. Reboot the immune system every 20 years or so to prevent it from ever getting old in the first place/

The stem cells to create blood and immune cells have to divide a lot. They get worn out.

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 "hematopoietic stem cells." Through cycles of cell division these stem cells preserve their own numbers and generate the daughter cells that give rise to 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, 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.

So your B cells get too old and tired and you never know whether the next person who sneezes in front of you is going to give you a bacteria or virus you'll be unable to defeat. Death awaits.

Why not enough helicase?

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 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.

Maybe low helicase is a helpful mechanism to cause old and damaged cells to die off. I would not assume that boosting helicase activity will necessarily extend life. Better to replace old cells with new cells rather than try to fix the old cells.

Share |      Randall Parker, 2014 August 01 09:25 PM 

Mangan said at August 7, 2014 8:08 PM:

A recent study showed that fasting for a couple of days can basically renew immune cells, so we already have the technology.

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