Autoantibody Mechanisms as a Basis for Therapies to Clear Senescent Cells

Senescent cells are those that have existed the cell cycle of continual division, due to either age or damage. They should destroy themselves or be destroyed by the immune system, but not all are, and that number increases greatly in older age, not least because the immune system declines and fails due to aging. Senescent cells that are not destroyed emit harmful signals to surrounding tissue, degrading function and encouraging more of their neighbors to also become senescent.

This paper looks at a mechanism by which the immune system clears out senescent cells. It is entirely plausible that these activities can be enhanced via suitable therapies, helping to greatly cut down the number of senescent cells hanging around to contribute to degenerative aging. Note that the paper is open access, but the full version available for download is PDF only.

Physiologic autoantibodies, that is, those with an active physiologic role, are an important part of the normal human immune system and are essential in maintaining homeostasis. Evidence suggests that the body uses autoantibodies to prevent disease and to self-treat diseases once started. This suggests a potential therapeutic role for autoantibodies, or, even better, a way to use them to prevent disease. Their capacity to remove aged, damaged cells is well established. Immunoglobulin (Ig) G autoantibodies bind to senescent cell antigen (SCA), which is an altered band 3 anion exchanger protein found mainly on aged cells. Once bound, IgG triggers the removal of the senescent cells by macrophages.

Band 3 is altered primarily by oxidation, which in turn generates SCA. These studies demonstrated that oxidation can generate neoantigens that the immune system will recognize. Band 3 isoforms are ubiquitous: they have been found in all mammalian cells and species so far examined.

The innate immune response to band 3 membrane proteins, and their regulation of cellular lifespan and therapeutic potential will be presented. Examples of other potential innate and physiologic autoantibodies include neuroprotective antibodies to amyloidgenic toxic peptides and antibodies to oxidized LDL (OxLDL), which modify the natural progression of atherosclerosis.



Possibly, modifying the old extra-cellular matrix will be necessary to keep cells from reverting to a senescent phenotype. See -

"Restoration of senescent human diploid fibroblasts by modulation of the extracellular matrix"

Also, according to the paper, modifying the old matrix may restore the cells it hosts to a more juvenile phenotype.

Posted by: Lou Pagnucco at September 29th, 2013 10:35 PM

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