On Targeting Senescent Cells to Treat Aging

Senescent cells accumulate with age, disrupting the tissues they are in, promoting inflammation, and undertaking a range of other bad behavior. Their presence is one of the causes of degenerative aging, and thus targeting them for destruction or reversal of their senescent state is a priority in longevity science:

Research has revealed that the presence of senescent cells is worse than one might think. These cells assume a special secretory form (SASP) in which they release various chemical signals that harm the health of nearby cells. In a domino effect they then damage their neighbors further accelerating the aging process.

A breakthrough study earlier this year showed that using specialized genetic methods to remove senescent cells throughout the lifespan of rats reduced signs of aging in the animals.

The current state of the science review article [is] written by two of the scientists who performed that study. In the paper they describe how senescent cells lead to aging in many tissues in the body. They further point out that aging of tissue is the reason for the development of diseases. "Therapeutic intervention in normal aging may prevent comorbidity and delay mortality in the elderly," they write. "In this way, targeting of senescent cells during the course of normal aging would be a preventative strategy rather than a treatment."

It is also pointed out that senescent stem cells may poison stem cell niches reducing the ability to regenerate and rejuvenate tissue so that removing them there could have diffuse age reducing benefit. Of course the big question is how senescent cells could be regularly removed from all over and within the human body other than embedding programmable genes before birth like was done in lab rats. The answers remain vague but the authors offer an idea, and some hope: "If a common signature is identified for senescent cells in vivo, strategies to alleviate these effects with compounds or drugs, whether by dampening the SASP profile or by completely removing the senescent cells, can begin to be elucidated."

Link: http://extremelongevity.net/2012/12/10/targeting-senescent-cells-to-reduce-human-aging/

Comments

These researchers make the following claim: "If a common signature is identified for senescent cells in vivo, strategies to alleviate these effects with compounds or drugs, whether by dampening the SASP profile or by completely removing the senescent cells, can begin to be elucidated." But the unique cellular signature for senescent cells that have the SASP profile has already been identified, and a novel intervention that exploits this signature has already been developed and demonstrated efficacious in vitro on human tissue(still waiting for results in animal models). I am referring to the work by the Spanish lab described in the following article:

http://www.sciencedaily.com/releases/2012/10/121003082728.htm

Not that the researchers in the article above (the Mayo clinic people) are wrong or anything; they just seem a little behind the times.

Posted by: gheme at December 12th, 2012 9:47 AM

But, the paper -
"Restoration of senescent human diploid fibroblasts by modulation of the extracellular matrix"
http://content.ebscohost.com/pdf25_26/pdf/2011/K8V/01Feb11/57290914.pdf
- gives evidence that the juvenile or senescent phenotypes are just different
guises that the same cells wear, depending on whether they are embedded in young or old extra-cellular matrices.

The phenotypes appear reversible when a cell is transplanted into different ECM.

Posted by: Lou Pagnucco at December 13th, 2012 12:05 AM
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