Mitochondrial dysfunction and cell senescence: deciphering a complex relationship

Increased oxidative stress in senescent cells is linked to dysfunctional mitochondria, and senescent cells show changes in mitochondrial mass, membrane potential and morphology.

“Increased oxidative stress in senescent cells has been linked to the accumulation of dysfunctional mitochondria. Indeed, senescent cells are characterized by changes in mitochondrial mass, membrane potential and mitochondrial morphology46”

An increase in ROS/RNS levels can be determined by mitochondrial dysfunctions and can contribute to telomere damage and epigenetic modifications.

“an increase in ROS/RNS levels can be determined by mitochondrial dysfunctions, and this can contribute to telomere damage and epigenetic modifications [27]”

Cellular senescence is a major mechanism of aging at the cellular level, though likely not the only one.

“Cellular senescence has been described as a major mechanism for aging at the cellular level, although likely not the only mechanism.”

Cellular senescence is a primary aging process and tumor suppressive mechanism with features including irreversible growth arrest, apoptosis resistance, SASP, mitochondrial dysfunction, and DNA/chromatin changes.

“Cellular senescence is a primary aging process and tumor suppressive mechanism characterized by irreversible growth arrest, apoptosis resistance, production of a senescence-associated secretory phenotype (SASP), mitochondrial dysfunction, and alterations in DNA and chromatin.”

Multiple inducers of cellular senescence include DNA damage, reactive metabolites, inflammation, oncogenes, mitogens, proteotoxic stress, and damage-associated molecular patterns.

“There are multiple inducers of cellular senescence, including DNA damage, reactive metabolites, inflammation, oncogenes, mitogens, proteotoxic stress, and damage-associated molecular patterns [16–18].”

Compared with normal proliferating or quiescent cells, senescent cells have increased mitochondrial mass, decreased mitochondrial membrane potential, potentially altered mitophagy, and increased mitochondrial ROS.

“Compared to normal proliferating or quiescent cells, senescent cells have increased mitochondrial mass, decreased mitochondrial membrane potential, potentially altered mitophagy, and increased levels of mitochondrial reactive oxygen species (Chapman et al., 2019).”