Senenscent Cells

What are Senescent Cells?

Cellular senescence is the phenomenon by which normal diploid cells cease to divide. In culture, fibroblasts can reach a maximum of 50 cell divisions before becoming senescent. This phenomenon is known as "replicative senescence", or the Hayflick limit.[6] Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. As such, cellular senescence represents a change in "cell state" rather than a cell becoming "aged" as the name confusingly suggests."

Senescent Cells are normal diploid cells that cease to divide. In culture, fibroblasts can reach a maximum of 50 cell divisions before becoming senescent. This phenomenon is known as "replicative senescence", or the Hayflick limit. Replicative senescence is the result of telomere shortening that ultimately triggers a DNA damage response. Cells can also be induced to senesce via DNA damage in response to elevated reactive oxygen species (ROS), activation of oncogenes and cell-cell fusion, independent of telomere length. As such, cellular senescence represents a change in "cell state" rather than a cell becoming "aged" as the name confusingly suggests.

Although senescent cells can no longer replicate, they remain metabolically active and commonly adopt an immunogenic phenotype consisting of a pro-inflammatory secretome, the up-regulation of immune ligands, a pro-survival response, promiscuous gene expression (pGE) and stain positive for senescence-associated β-galactosidase activity. Senescent cells affect tumour suppression, wound healing and possibly embryonic/placental development and a pathological role in age-related diseases.

Why do we have senescent cells?

Scientists think that this cellular birth controlmay have evolved to thwart the formation of tumors, but there are other benefits as well. Senescent cells release chemicals that help wounds heal, for instance. But senescence also causes harm. If stem cells stop dividing, organs can deteriorate since new cells cannot be produced. Furthermore, the chemicals released by senescent cells can damage surrounding tissues and, and may actually promote tumor growth.

Removal of Senescent Cells

As animals age, cells that are no longer able to divide — called senescent cells — accrue all over their bodies, releasing molecules that can harm nearby tissues. Senescent cells are linked to diseases of old age, such as kidney failure and type 2 diabetes. (Ref 1)

The presence of senescent cells can cause additional problems: they degrade tissue function, increase levels of chronic inflammation, and can even eventually raise the risk of cancer. Senescent cells normally destroy themselves via a programmed process called apoptosis and they are also removed by the immune system, however the immune system weakens with age and increasing numbers of these senescent cells escape and build up in the tissue.

The elimination of senescent cells from transgenic progeroid mice and non-progeroid, naturally-aged mice led to greater resistance against aging-associated diseases.

A newly formed company Unity Biotechnology formed by Jan van Deursen, who studied senescent cells at the Mayo Clinic College of Medicine in Rochester, Minn. focuses on creating drugs that clear senescent cells from the body.

Recent work published in Nature by Jianhui Chang et. al., .."We show that ABT263 selectively kills SCs in culture in a cell type– and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells..."

ABT263 Molecular Struture from PubChem

 

Readings and References

1--Destroying worn-out cells makes mice live longer --Elegant experiment confirms that targeting senescent cells could treat age-related diseases.

2- Suicide of aging cells prolongs life span in mice

3-Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice