November 27, 2011 1:21:23 am
Until recently,few people gave much thought to senescent cells. They are cells that linger in the body even after they have lost the ability to divide. But on November 2,in what could be a landmark experiment in the study of ageing,researchers at the Mayo Clinic in the US reported that if you purge the body of its senescent cells,the tissues remain youthful and vigorous.
The experiment was in mice,and it cleared the cells with a genetic technique that cannot be applied to people. Like all critical experiments,it needs to be repeated in other labs before it can be accepted with confidence. But the startling result is plausible because it ties together an emerging body of knowledge about senescent cells. And raises the possibility that attacks on the cells might postpone the diseases of ageing.
Senescent cells were discovered 50 years ago in an experiment by the biologist Leonard Hayflick. He found that human cells cultured in glassware do not multiply indefinitely,as was then assumed,but can divide only 50 or so times before lapsing into senescence. Simple organisms live short lives and do not need cell division. More complex animals live longer because their tissues are renewable. In humans,the cells lining the gut are renewed every five days. Red blood cells last 120 days. Even bone cells slowly turn over,with the result that the entire skeleton is renewed every 10 years or so.
But the price for renewable tissues is cancer: If cells are capable of division,any damage to their control systems can lead to unconstrained growth. The body has therefore evolved two major systems to curb the risk of cancercell senescence and cell death. Both systems are set in motion by illicit cell divisions,like those caused by a virus; by damage to DNA; or by activation of tumour-causing genes. Senescence can also be caused when cells run out of telomeres,the caps at the end of the chromosomes that get shorter at each cell division. This route to senescence,discovered in the 1990s,underlies the process observed by Hayflick.
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Cells thrown into senescence do not divide again but hang about in tissues until they are cleared by the immune system. In cell death,a cell is forced to set off a built-in suicide mechanism. Researchers do not yet understand why there are two systems,or how the body chooses whether to assign a damaged cell to senescence or to death. But a benefit of senescence is that suspect cells can continue to perform vital functions,said Daniel Peeper,an expert on senescence at the Netherlands Cancer Institute in Amsterdam. Senescent cells seem to be a benign byproduct of the bodys defense against cancer. But researchers have developed growing suspicions of a less benign aspect: the cells culpability in ageing. Senescent cells accumulate throughout life,probably because the immune system sweeps them away less efficiently as a person ages. Larger and flatter than normal cells,they are especially common in tissues showing signs of ageing,like arthritic knees or the plaque in the arteries.
And despite being termed senescent,they are very active: They convert themselves into factories that churn out 100 different kinds of growth factors,along with cytokines,the inflammatory agents that stimulate the immune system. The evolutionary reason for this activity may be to provoke the immune system to attack patches of premalignant and malignant cells.
But the process turns out to have some untoward side effects. As it happens,many ageing tissues show signs of chronic inflammation,which can foster age-related diseases,including arthritis,Alzheimers and cancer. The relationship between ageing and inflammation has so far been a mystery. The Mayo Clinic researchers,a team led by Jan M. van Deursen and Dr James L. Kirkland,have come up with a clear answer: Its the senescent cells that inflame the tissues and cause them to age.
Senescence is induced in most cells by the activation of two genes,known as p53 and p16-INK4a,that are the guardians and enforcers of proper cell division. When they detect any damage in the cells controls,they force it into either senescence or death. The researchers showed that mice purged of senescent cells could run much longer on a treadmill,had larger fat depositsfat disappears from the skin as people age,causing wrinklesand developed cataracts much later. Much the same effect was seen in a second experiment,in which dosing did not start until the mice were middle-aged,except that cataracts that had already formed could not be reversed.
The experiment strongly suggests that accumulation of senescent cells does contribute to ageing,and they show that by eliminating senescent cells they could delay premature ageing, researchers said. NICHOLAS WADE
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