August 21, 2008
Senescent Liver Cells Protect Against Fibrosis And Cancer

One of the hopes for rejuvenation therapies is to develop biotechnologies that can induce senescent (old and barely functioning) cells to commit suicide in order to make room for healthier cells to divide and take their place. But senescent cells serve useful functions.

Although post-reproductive life in humans is often associated with decline and a loss of powers, an analogous state in certain cells -- called senescence -- is proving to be one of ironic potency. Scientists at Cold Spring Harbor Laboratory (CSHL) today reported that a particular class of senescent liver cells orchestrates a sequence of events in living mice that can limit fibrosis, a natural response of the liver to acute damage.

The surprising finding follows on the heels of experiments conducted by the same CSHL team last year linking senescence in liver cells with the organ's ability to fight off liver cancer, also called hepatocellular carcinoma, or HCC.

The new findings are the first to establish a specific role for cellular senescence in a non-cancer pathology, and, the CSHL team notes, suggests a new therapeutic approach that could help human patients with precursors of serious liver diseases such as cirrhosis, which is the 12th most common cause of death in the United States.

Of course we need cures for cancer anyway. But these results might be the tip of the iceberg in terms of useful purposes served by senescent cells.

My fear on rejuvenation therapies is that it might be necessary to orchestrate many forms of repair at once in order to keep cells and metabolism in balance. If destroying senescent cells will increase the incidence of other forms of disease and malfunction then we will at least need to weigh the relative risks of treatment versus non-treatment.

Fibrosis can happen in a variety of organs and so senescence might protect against fibrosis in many parts of the body.

" Fibrosis is a disease of many organs—lungs, kidneys, pancreas, prostate, skin," said Valery Krizhanovsky of Cold Spring Harbor Laboratory. "It's possible this mechanism in the liver is relevant to fibrotic situations in other tissues."

The state of cell-cycle arrest known as senescence was first described decades ago, but the phenomenon was thought to occur only in cultured cells in the laboratory, Krizhanovsky explained. More recent studies found that cellular senescence helps protect against the formation of tumors and aids in the response to certain anticancer agents.

Interestingly, the researchers said, senescent cells had also been observed in some aged or damaged tissues, including the cirrhotic livers of human patients. However, the functional contribution of cellular senescence to diseases other than cancer hadn't been examined.

Of course, just as better cancer treatments could eliminate concern that cancer could come as a complication of rejuvenation therapy a better treatment for fibrosis could eliminate the need for senescent cells to protect against fibrosis.

Update: Note that the need to leave senescent cells in place goes way down once we can replace whole organs. No need for senescent cells to suppress nearby cancer cells if all the cells in an organ are youthful and relatively undamaged. Grow new organs from a well tested stem cell line and then when, say, a new youthful liver replaces an old liver we get rid of the senescent cells and the precancerous cells at the same time.

Share |      Randall Parker, 2008 August 21 10:34 PM  Aging Mechanisms

Dan V said at August 22, 2008 11:04 AM:

Not to oversimplify the matter, but I consider these findings almost irrelevant in terms of the goals of rejuvenation studies. When we take a look at the overarching goal of rejuvenation efforts, it is to make the old young again. We're trying to restore the aged human body to a youthful state. In that youthful state, we're far less vulnerable to cirrhosis and cancers than we are in an aged state with whatever protection senescent cells offer against these ailments. This is very likely to be unilaterally true of all diseases. So, whatever benefits senescence offers the elderly, youth offers much better benefits. If the removal of senescence or senescent cells is on the list of actions needed en route to that youthful restoration, than it seems obvious that we should ignore their benefits.

That's not to say these findings are in fact useless, just irrelevant to the aims of efforts in agelessness.

mark b. said at August 22, 2008 1:51 PM:

Great post... I think this suggests we can look forward to many unanticipated consequences of genetic engineering... When you turn one light off, another goes on.

Randall Parker said at August 22, 2008 5:14 PM:

Dan V,

If we replace an entire old liver with one grown from youthful stem cells then we'll remove both the senescent cells and the cells that are prone to cancer. That'll probably be a net win. But if we remove only the senescent cells we could create potentially fatal problems for ourselves due to higher risk of cancer and fibrosis.

Bob Hawkins said at August 23, 2008 5:38 AM:

Using senescent liver cells to prevent fibrosis. Evolution is such a hacker.

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