Table 2.

Features of senescent cells that may or may not serve as hallmarks of a state of cellular senescence and may or may not be used as diagnostic biomarkers of senescent cells existing in organismal tissues

Affected aspect of cell morphology and function	Feature of senescent cells	Observed		Can serve as a hallmark/diagnostic biomarker of senescent cells	References
		in vitro*	in vivo**
Cell morphology	Cell multi-nucleation and extensive vacuolization	✓	?	?	22, 263
Cell motility and adhesion	Reduced cell motility; enhanced focal adhesion of cells to the extracellular matrix	✓	?	?	140, 264, 265
Cell-cell contact	Reduced efficacy of cell-cell contacts	✓	?	?	86, 140
Glycogen	Accumulation of glycogen granules, inactivating phosphorylation of the glycogen synthesis inhibitor GSK3, and activating dephosphorylation of glycogen synthase	✓	✓	?	140, 143, 266, 267
Cytoskeleton	Reduced cellular level of actin; nuclear accumulation of G-actin, jointly with an active phosphorylated form of the actin depolymerizing factor cofilin	✓	✓	?	140, 268–270
	Elevated cellular level of the intermediate filament protein vimentin; elongation, condensation and linearization of the intermediate filaments containing vimentin	✓	✓	?	140, 271–273
	Increased number of microtubule organizing center, which nucleates individual microtubules	✓	?	?	140, 274
Lysosomes	Enhanced expression of numerous genes encoding lysosomal enzymes	✓	?	?	140, 143, 147, 148
Mitochondria	Reduced efficacy of mitochondrial fission and the resulting shift of the balance between mitochondrial fission and fusion towards fusion	✓	?	?	140, 147, 155, 156
Autophagy	Reduced efficacy of chaperone-mediated autophagy and non-selective macroautophagy, including mitophagy	✓	?	?	114, 115, 125, 275–279
Nucleus	Aberrant shape of the nucleus; reduced levels of the lamin A-associated protein LAP2 and several other nuclear proteins	✓	✓	?	140, 166, 280, 281
Chromosomes	Chromosomal instability exhibited as polyploidy or aneuploidy	✓	✓	?	263, 282–288
Senescence-associated microRNAs (SA-miRNAs)	Expression of numerous SA-miRNAs is altered (either elevated or reduced) in cultured cells undergoing senescence caused by cell exposure to various triggers of either replicative or premature (stress-induced) mode of cellular senescence; many of these SA-miRNAs play essential roles in regulating senescence of cultured cells by targeting the signaling circuitry characteristic of the cellular senescence program; at least one of these SA-miRNAs, miR-22, can induce cellular senescence in vivo	✓	?	?	112, 113, 289–296
Apoptosis	Resistance to apoptotic cell death elicited by certain pro-apoptotic stimuli	✓	?	?	12, 196–202

^*Observed in cells entered a state of senescence in culture.

^**Observed in senescent cells recovered from organismal tissues.