What is a senescent cell? 

Principally, a senescent cell is one characterized by entering a state of arrest of division and growth, while remaining metabolically active, resistant to cell death. A senescent cell is also typically characterized by a secretory phenotype, including chemokines, cytokines and other factors that may alter the extracellular matrix. Although a senescent cell currently does not have a generally agreed, precise definition, in the scientific community, in part due to limited in vivo experimentation, senescent cells are generally considered to be rare in tissues and of large size, to have a number of known molecular characteristics that distinguish them, and many more under active investigation. Debate remains regarding the degree to which senescent cells are exclusively damaged cells such as from oxidative stress and DNA damage versus arising from normal aging such as telomere shortening. Similarly, senescence appears to have beneficial characteristics including limiting the growth of damaged or potentially cancerous cells but also appears to accumulate in tissues over time contributing to age-related diseases and functional decline. Molecularly speaking, transcriptional and proteomic expression profiles and specific biomarkers may be considered hallmarks of senescence, which may be terminal for the cell, that may be programmed or damage-induced or represent features to be recognized by the immune system, or others. Similarly, senescent cells may affect neighboring cells, perhaps as a gradient in the tissue or in regard to cell lineage.It is generally agreed that many common features exist among senescent cell types, but that they are heterogeneous across tissues, and that the complexity of classifying these warrant scientific investigation to better understand and make use of these characteristics to improve human health.

Is senescence a tissue specific characteristic?

To different degrees, senescence affects many cell types, across all tissues. Senescent cells of specific cell types, in each tissue, and each tissue state of maturation or disease or stimuli across the lifespan, likely present a differential set of molecular characteristics. There may be a minimal universal set of characteristics that may serve as a “core molecular signature” of senescence, but these are not yet widely agreed other than a few notable biomarkers. 

Is senescence a characteristic of a region of tissue or a cell? 

Senescence can be a characteristic at the cell, cell region, or tissue level. Individual cells do have a specific state, and in general senescence is considered a cell characteristic,  but that can be microenvironment-dependent, in a feedback loop. The abundance of senescent cells can be found in different regions of tissue distinct from surrounding cells in their molecular expression, morphology, and metabolism. Senescent cells can secrete factors that affect neighboring cells and contribute to changes in tissue function. Senescence may appear more around blood vessels. While senescence is a characteristic of individual cells there may be consequences for the tissue as a whole.

Is the senescent cell a signaling cell?

Yes, senescent cells secrete factors that recruit the immune system, induce apoptosis and senescence in surrounding cells via the senescence-associated secretory phenotype (SASP), which is characterized by the production of a range of signaling molecules such as cytokines, chemokines, growth factors, and proteases, including exosomal release which can travel throughout the body. The SASP can attract immune cells to clear damaged or potentially cancerous cells while chronic SASP signaling can contribute to chronic inflammation, tissue damage, and age-related diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. At the same time stress upon cells and tissues from disease pathology results in an increase in senescent cells making them both signaling and effector cells. Learning more about surface markers and how they are driven in time, location, and other dynamics such as interactions with other cells, and senescent cell clearance versus disease cell clearance is needed to develop fundamental understanding that may improve human health.