Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: OneIn VivoReality, Two Possible Definitions?

Abstract

No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1). Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2). As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2) appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (patho)physiology and aging.

Metformin lowers the threshold for stress-induced senescence: A role for the microRNA-200 family and miR-205

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“…The appearance of senescence during short-term expansion is a sign of non-optimal culture conditions, since senescence is one of the responses of the cells to stress (stress-induced premature senescence) [21]. No expression of β-galactosidase and, consequently, no cellular senescence was detected.…”

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“…51 These results show that comparisons between different species may be biased due to inter-species differences in O 2 sensitivity; instead of showing maximum cellular proliferate capacity, these results show O 2 sensitivity. 52 In addition, since there is a positive correlation between body size and longevity, 53 perhaps cells taken from long-lived animals endure more CPDs because of the difference in size, not due to the difference in longevity.…”