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  • « Thoughts on Engineered Longevity and Selfishness | Main | Biomarkers of Aging at SAGE Crossroads »

    Wednesday, August 13, 2008

    On Dealing With Senescent Cells

    As I've noted in the past, accumulation of senescent cells over the years is one of the root causes of age-related damage, disease, degeneration, and ultimately death:

    So-called 'senescent' cells are those that have lost the ability to reproduce themselves. They appear to accumulate in quite large numbers in just one tissue (the cartilage in our joints), but even in these small numbers they appear to pose a disproportionate threat to the surrounding, healthy tissues, because of their abnormal metabolic state. Senescent cells secrete abnormally large amounts of some proteins that are harmful to their neighbours, stimulating excessive growth and degrading normal tissue architecture. These changes appear to promote the progression of cancer.

    Why do senescent cells accumulate with age? It is possible that the aging immune system, suffering issues of its own, no longer destroys senescent cells efficiently enough. It is also possible that accumulation of senescent cells has a lot to do with the shortening of telomeres with age: telomeres, after all, shorten with each cell division to act as a clock that moves cells from the life cycle of division and growth into either a quiescent or senescent phase.

    You'll find a couple of interesting posts over at Anti-Ageing Research summarizing the issue of senescent cells and outlining ways to approach the repair and reversal of this age-related change in our bodies:

    Cellular Senescence in Anti-Ageing Research:

    Since senescent cells are potentially detrimental to the tissues in which they reside, anti-ageing research has three main aims for dealing with this problem:

    (1) Prevention: prevent cells from becoming senescent.
    (2) Removal: remove senescent cells as they appear.
    (3) Replacement: replacement of cells which have naturally or artificially been removed.

    ..

    Therapeutic agents have the potential to specifically target senescent cells and induce programmed cell death (apoptosis). At present, no such drug is available. However, drugs that are being developed to specifically target cancer cells could one day be adapted to target senescent cells. For this to be made possible, a cell surface marker specific to all senescent cells needs to be identified. A drug can then be developed which specifically identifies that marker, binds to it and induces apoptosis.

    The removal of senescent cells using therapeutic agents:

    One promising area of research in the development of drug delivery systems incorporates the use of nanotechnology. Such technology has been used to create dendrimers, spheroid or globular nanostructures which are highly branched. The branched regions of these dendrimers can be used to attach molecules such as targeting and therapeutic agents. To test this nano-delivery system, [investigators] attached a targeting agent, a therapeutic agent and an imaging agent to the surface of dendrimers. The investigators chose folic acid as the tumour-targeting agent (a molecule which binds to a high-affinity receptor found on many types of tumour cells).

    ...

    The dendrimer construct was highly toxic to [cancer cells with folic acid receptors] but had no effect on cells without the folic acid receptor. It is research like this that could one day be adapted to specifically target senescent cells.

    The tools of biotechnology being developed for specific uses today - often in the cancer research community - will have very broad future applications. Nanoparticles like dendrimers are one example of many.

    Posted by Reason at August 13, 2008 7:07 PM | TrackBack (0)

    Posted by: Michael G.R. at August 14, 2008 1:04 PM

    Off topic:

    Hi Reason,

    Have you given more thought to ways of getting a larger audience? Any news on maybe being part of the SEED network of blogs or something like that?

    Just curious. Thanks.

    [Posted by: Michael G.R. at August 14, 2008 1:04 PM]

    Posted by: Reason at August 14, 2008 5:59 PM

    No changes to my prior thoughts on the topic, but it seems that SEED isn't all that interested.

    [Posted by: Reason at August 14, 2008 5:59 PM]

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