Rapamycin Influences the Senescence-Associated Secretory Phenotype

It should not be at all surprising to find that the more reliable methods of modestly slowing aging in mammals have an impact on cellular senescence, one of the root causes of aging. Based on the evidence to date, most of these methods are thought to slow aging across the board, influencing all measures of degeneration, though there is some debate over the degree to which rapamycin works by suppressing cancer risk rather than via other mechanisms. Senescent cells accumulate with age, but not to more than a few percent by number in most tissues even in older individual. They cause harm primarily through signaling mechanisms: a senescent cell generates what is known as the senescence-associated secretory phenotype (SASP), a mix of compounds that create inflammation, damage the structures of the extracellular matrix, and alter the behavior of surrounding cells for the worse. Removing senescent cells will deal with this problem, but some research groups are determinedly following the much harder path towards finding ways to reduce or modulate the SASP in order to reduce its harmful effects.

Researchers have found that a compound called rapamycin has unusual properties that may help address neurologic damage such as Alzheimer's disease. The newly-discovered mechanism is what researchers say might help prevent neurologic damage and some related diseases. "The value of rapamycin is clearly linked to the issue of cellular senescence, a stage cells reach where they get old, stop proliferating and begin to secrete damaging substances that lead to inflammation. Rapamycin appears to help stop that process." This secretion of damaging compounds creates a toxic environment called senescence-associated secretory phenotype, or SASP. It's believed this disrupts the cellular microenvironment and alters the ability of adjacent cells to function properly, compromising their tissue structure and function. This broad process is ultimately linked to aging.

"The increase in cellular senescence associated with aging, and the inflammation associated with that, can help set the stage for a wide variety of degenerative disease, including cancer, heart disease, diabetes, and neurologic disease such as dementia or Alzheimer's. In laboratory animals when we clear out senescent cells, they live longer and have fewer diseases. And rapamycin can have similar effects."

Prior to this research, it had only been observed that there was one mechanism of action for rapamycin in this process. Scientists believed it helped to increase the action of Nrf2, a master regulator that can "turn on" up to 200 genes responsible for cell repair, detoxification of carcinogens, protein and lipid metabolism, antioxidant protection and other factors. In the process, it helped reduce levels of SASP. The new study concluded that rapamycin could also affect levels of SASP directly, separately from the Nrf2 pathway and in a way that would have impacts on neurons as well as other types of cells. "Any new approach to help protect neurons from damage could be valuable. Other studies, for instance, have shown that astrocyte cells that help protect neuron function and health can be damaged by SASP. This may be one of the causes of some neurologic diseases, including Alzheimer's disease."

Link: http://oregonstate.edu/ua/ncs/archives/2017/apr/new-function-discovered-compound-may-help-slow-aging

Comments

Their aim is irrelevant as long as they keep wasting time on metformin and rapamicyn.

Posted by: Anonymoose at April 6th, 2017 11:23 AM

Once we start with these rejuvenating therapies, evolution will work in our favor, as we will become more aware of beneficial mutations within our species. The senescent cell clearance therapies might be all we need to do to start the ball rolling. Exciting times we are living in.

Posted by: Tj Green at April 6th, 2017 5:33 PM

Another Carrington event, a VEI 7 eruption like Thera is all it takes to send us all to the grave long before any of this is done. The sooner the better.
The fact that global catastrophic risks and rejuvenation is not funded almost at all compared to the size of their danger is testament to our unintelligent design.

Posted by: Arren Brandt at April 8th, 2017 12:19 PM

Oh yeah that should have read "The sooner we get rejuvenation done, the better". I'm not wishing us all to the grave. Sorry.

Posted by: Arren Brandt at April 8th, 2017 12:20 PM

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