Senescent Toxins

Senescent toxins (from Latin: senescere, meaning “to grow old,” and Ancient Greek: τοξικόν toxikon) are poisonous molecules that cause cells to age. Cellular aging is the committed arrest of a cells growth phase to a more differentiated state commonly referred to as replicative senescence. Cells that have been induced by toxins to no longer divide stand apart morphologically from other cells as being flattened and larger. Often senescent toxins disrupt mitotic function and lead to incorrectly formed nuclei. These damaged nuclei trigger apoptosis to alleviate any harm a damaged cell may cause to neighboring cells. When toxins cause malfunctions in mitosis it is likely that the mitotic checkpoint in the cell cycle is compromised as a direct impact from this poisoning. Senescent toxins can be generated by an organism or introduced into one organism by another. Senescent toxins cause chemical modifications to cells and accumulate as aggregates of proteins, which in turn can cause: alteration of gene expression, disruption of enzymatic activity, and disruption of signaling pathways. These implications instigate a slowing of cellular repair functioning due to increased demand. As cell repairs slow, this leads to an overall lower quality immune system for an organism. An inefficient immune system cannot defend against attacks and further damage from these attacks leads to more aging at an increased rate of occurrence. These negative impacts are exacerbated in tissues with cells that do not replicate throughout the life cycle of the organism like human heart cells. When one heart cell ages, its workload is passed to a properly functioning heart cell, leading to that healthy cell aging prematurely from additional strain. Another extreme dilemma is when stem cells are aged and destroyed. This means a high population of old cells are not being replaced. Scientists studying the effects of ageing (bio-gerontologists) are concerned with the varying impacts of these toxins, because outcomes are not always the same. When a cell has become cancerous it is a successful strategy for the cell to utilize senescent toxins to cause programmed cell death to stop the diseased cells from perpetuating, as with Heat Shock Protein 60.

Protein Senescent Toxins

The senescing of cells is concerted, it either happens or it does not. When senescing toxin concentration outweighs the non-senescing factors concentration, a shift to age the cell occurs. A group of senescent toxins that are found to do this are heat shock proteins (HSP’s). HSP’s are commonly known for refolding stressed proteins in conditions such as hypoxia (medical) and hyperoxia. However, HSP60 has been found to exist at high levels in senescing cells. Experiments have shown removing or disrupting HSP60 from senescing cells stops senescence in a cell that requires it. HSP60 has been found to assist in the Caspase-3 apoptotic pathway. HSP’s are not only chaperone proteins, but also senescent toxins. Another protein, which can exist as a senescent toxin, is P21. The P21 protein is a cyclin dependent kinase inhibitor which functions to regulate the cell cycles progress in the G1 phase. An excess accumulation of P21 in the nucleus of human cells was found to lead to premature cellular senescence.

Senescent Toxin Assays

Bio Vision Incorporated develops and offers a wide variety of products including assay kits, antibodies, and recombinant proteins and enzymes. They also make innovative research tools for studying apoptosis, metabolism, cell proliferation, cellular stress, cell damage and repair, diabetes, obesity and metabolic syndrome, stem cell biology, gene regulation, and signal transduction. One assay is a senescence detection kit, which uses nuclear extract prepared from HeLa cells that contain a variety of DNA-binding proteins, transcription factors, and other nuclear proteins.