Abstract
Replicative senescence is an unalterable growth arrest of primary cells in the culture system. It has been reported that aging in vivo is related to the limited replicative capacity that normal somatic cells show in vitro. If oxidative damage contributes to the lifespan limitation, antioxidants are expected to extend the replicative lifespan of fibroblasts. This article critically reviews the results of experiments devoted to this problem performed within the last decades under conditions of in vitro culture. The results of studied are heterogeneous, some papers showing no effects of antioxidants; most finding limited enhancement of reproductive capacity of fibroblasts, some reporting a significant extension of replicative lifespan (RLS). Both natural and synthetic antioxidants were found to extend the RLS of fibroblasts, either by a direct antioxidant effect or, indirectly, by activation of signaling pathways and activation of proteasomes or hormetic effects. Most significant prolongation of RLS was reported so far for nicotinamide, N-hydroxylamines, carnosine and Methylene Blue. These results may be of importance for the design of skin-protecting cosmetics.
Highlights
The skin is the largest and the most visible organ of the human body
This theory implies that stem-like cells that are not committed to senescence are present in early passage fibroblast populations, but they give rise to committed cells with finite lifespan
Protein carbonyl content increases in senescent fibroblasts [31], one study reported a decrease in this content [22]
Summary
The skin is the largest and the most visible organ of the human body. Aged skin is biologically characterized by the flattening of the dermal-epidermal junction and a general atrophy of the extracellular matrix (ECM) with disorganized and reduced collagen and elastin. The number of dermal fibroblasts decreases with aging; this phenomenon, along with impairment of functional capacities of the remaining cells results in decreased ability to synthesize active soluble factors and to maintain proteostasis of components of the ECM. The variability of the results of in vitro longevity studies can be explained on the basis of the commitment theory of cellular aging. This theory implies that stem-like cells that are not committed to senescence are present in early passage fibroblast populations, but they give rise to committed cells with finite lifespan. This study is aimed at summarizing the available data on this subject
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