Aiming to Remove the Senescent Cell Contribution to Aging and Age-Related Disease
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As the years pass ever more of your cells fall into a state of senescence. This is a response to the age of the cell itself, its internal damage, surrounding levels of metabolic waste, the presence of cell-damaging toxins, or other signals that indicate a potentially raised risk of cancer. Senescent cells do not divide or do much else to support the tissue they are a part of, but rather emit a range of potentially harmful chemical signals that encourage other nearby cells to also enter a senescent state. Senescent cells sometimes self-destruct, or they can be removed by the immune system, but the immune system has its own process of age-related decline and this activity falters. Cellular senescence can indeed reduce the risk of cancer, but by the time there are significant numbers of senescent cells gathered in the body their presence causes all sorts of harm: they degrade tissue function, increase levels of chronic inflammation, and can even eventually raise the risk of cancer due to their generally bad behavior.

Cellular senescence is one of the more exciting areas of the biochemistry of aging, because the research community is very close to being able to produce treatments for the targeted, safe removal of senescent cells. Early animal studies have provided initial evidence that doing so does produce improvements in health and longevity, as expected. Further studies in rodents presently in progress should firmly demonstrate that healthy, normal animals benefit from the removal of senescent cells. After that, it is a matter of pulling together the targeted cell killing techniques pioneered by the cancer research community with one of the new prospective methods for accurately distinguishing senescent cells from their healthy peers. If not for the generally slow, expensive pace of medical regulation this is something that could probably be done within the next five years, or much sooner for technology demonstrations in laboratory animals.

Targeted destruction of senescent cells is an excellent candidate for a treatment that, like early stem cell therapies, could be offered outside the US for years prior to the more formal and straitjacketed medical development community coming to the point of trials. All the prototype parts of the toolkit are nearly ready, and a successful treatment to remove unwanted senescent cells would be an unalloyed benefit for any healthy older adult. Sadly, as is the case for near all of the most important areas of longevity science, there is little interest or funding for this work in comparison to its potential benefits to health. Things are moving more rapidly than for many other important areas of aging research, but funding is still at disappointingly low levels. We can hope that this will change at the point at which it becomes viable to offer prototype clinical treatments via medical tourism, in much the same way as matters proceeded for the development of the first stem cell therapies.

Here is the latest in a series of essays on the details of the SENS vision for rejuvenation therapies penned by philanthropist Jason Hope. Hope is one of the more noteworthy donors to the SENS Research Foundation, and clearly believes in the goals he supports:

Death Resistant Cells

There are two main approaches to the problems associated with senescent cells: develop a drug that is toxic to abnormal cells but harmless to healthy ones, or stimulate an immune response that targets and selectively kills unhealthy cells.

Molecules lining the surface of cells help those cells interact with their surroundings; these molecules are to varying degrees distinctive to their fate. Because each type of cell has different surface molecules, these molecules can serve as markers, or identification for that cell. Liver cells have a different group of molecules on their surface than blood cells, for example.

Abnormal cells have abnormal surface molecules, making these cells easy to target for therapy. Oncologists already use this type of approach when treating some types of cancer with the intent of shutting down the cancer cells' growth with drugs or by stimulating the immune system to do the job. In some cases, killing abnormal cells deters, treats, or prevents illnesses by making room for new, healthy cells.

Using SENS Research Foundation funding, scientists from University of Arizona are investigating ways to restore a healthy immune system in aging mice by purging unhealthy immune cells known as "anergic T-cells" to free up space for new and healthy killer T-cells. The researchers also hope to bolster the immune system by increasing the body's ability to produce new killer T-cells.

With funding from SENS Research Foundation and working in Dr. Judith Campisi's laboratory at the Buck Institute for Research on Aging, PhD candidate Kevin Perrott is investigating how molecules affect one type of senescent skin cell to understand its role in inflammation and the immune system. These scientists also hope to discover how to kill these senescent cells before they can cause a problem. Additionally, these researchers are testing a library of compounds to identify any that are capable of selectively targeting senescent cells.

SENS Research Foundation funding also supports research performed by Nick Schaum in the Campisi lab, which has shed light on the link between the two hallmarks of cell senescence, identifying a key driver of inflammation and halted cell division.

The goal of these research projects is to understand how cell programming can cause illness and to develop ways to control cell senescence, either through therapeutic drugs or by stimulating the immune system so that it destroys only abnormal cells while leaving healthy cells intact. Success will lead to new rejuvenation biotechnologies to prevent, treat, and even reverse the course of the disease and disability caused by these abnormal cells.

Comments

I'm hoping that someone manages to safely remove senescent cells in a mouse soon using a technique applicable to adult humans. This technology may then perhaps get picked up by a big pharma company or biotech like sirtuins did.

Posted by: jim at July 11, 2014 10:10 AM

I propose to create a drug (selective "neoBotox") that would selectively destroy the old cells in vivo (to make way for young or rejuvenated stem cells). For example, senescence-associated β galactosidase substrate, which, under the influence of this enzyme, will release the potent toxin. Such a selective toxin would be useful for the rapid elimination from the body of old cells which are the source of aging niche components. At low concentrations of the drug or target delivery (eg, by exosomes with selective receptors to aged cell) into the cell it should not damage the cells with low concentrations of senescence-associated β galactosidase, but will destroy the cells with high concentrations of it.

Posted by: Dmitry Dzhagarov at July 13, 2014 3:07 AM

Существует такое направление в онкотерапии - онкотропные и онколитические вирусы.
А что, если попытаться получить сенотропные и сенолитические вирусы?

Posted by: Зиновий Белкин at April 16, 2015 9:24 AM
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