ReviewFree radicals and senescence
Section snippets
Ambient oxygen and cellular senescence
The observations by Hayflick that normal human diploid cells have a finite number of population doublings [1] provided the impetus for many other laboratories to begin to define the genetic and environmental factors regulating in vitro senescence. There was considerable concern initially that senescence was not an intrinsic property of cells and that it was the artificial nature of tissue culture systems that was in some way responsible for limiting the growth of cells. For instance, many were
Oncogene-induced senescence: a role for ROS
As noted above, senescence can be induced simply by growing cells in culture (replicative senescence) or by subjecting cells to non-lethal stress such as hydrogen peroxide. A significant insight into the potential physiological relevance of senescence came with the observation that primary cells with high level expression of the Ras oncogene underwent rapid senescence [15]. These results were unexpected because the property of oncogenes was routinely associated with uninhibited and increased
Senescence, ROS and disease
The original ‘Free Radical Theory of Aging’ postulated that ROS contributed not only to the rate we age but also served as the impetus for a number of age-related diseases [26]. There are numerous studies suggesting that oxidants might contribute to a wide spectrum of human maladies including cancer, cardiovascular disease and a host of neurodegenerative conditions [6]. There is also a growing body of literature suggesting that senescence within progenitor cells or resident mature cells might
Summary
On a cellular level there is abundant evidence that a rise in ROS levels contributes to senescence. Nonetheless, multiple questions remain. One unresolved issue is whether there is a gradient of ROS-induced effects. This notion was first inferred from the addition of exogenous hydrogen peroxide where it was clear that in some cells, very high doses of hydrogen peroxide (> 1 mM) induced cell death, moderate doses (100–500 μM) induced senescence, while lower doses either were without effect or
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2022, CytotherapyCitation Excerpt :Cell manufacturing efficiency may improve, as faster growth will decrease the time to reach required cell production levels, reducing exposure to potential harmful cell stress and decreasing manufacturing costs via fewer passages. Although the present study showed no significant effect on senescence, the authors believe that O2 accelerates senescence, as has been demonstrated in several in vitro models, including MSC models [14,15,54]. Cardiovascular Cell Therapy Research Network research reported in this article was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health under award number UM1HL087365.