Sirs, Although the influence of lipofuscin on cells and lysosomes is debated, it is considered to be either insignificant or damaging (reviewed in Terman et al. 2007; Kurz et al. in press; Brunk and Terman 2002). Recently, however, a paper (Stroikin et al. 2007) was published in Biogerontology that attributed to lipofuscin a new and stabilizing effect on lysosomes of starved fibroblasts. In that study it was concluded that lipofuscin in moderate amounts renders cells more, not less, resistant to starvation. Unfortunately, the experimental design does not seem to justify such conclusions. The cellular amount of lipofuscin was varied by growing cells for prolonged periods of time (months) at either 8% or 40% ambient oxygen, being an established method to restrict or enhance, respectively, lipofuscin formation (reviewed in Brunk and Terman 2002). The cellular response to oxidative stress, induced by starvation (Gaspar et al. 2006; Morales et al. 2004; Eisler et al. 2004), was then compared on the two groups of cells. However, growing cells at 40% oxygen also means exposing them to a condition of moderate oxidative stress and thereby preconditioning them to, and protecting them from, a later, more marked oxidative stress. This fact is described in relevant literature (Spitz et al. 1987; Tang et al. 2005; Fonager et al. 2002). In contrast, this is not the case for cells that have been grown at 8% oxygen before an ensuing oxidative stress. Therefore, the two groups in the study (Stroikin et al. 2007) were not directly comparable when they were exposed to starvation. Consequently, the observation that lipofuscinladen cells appeared more resistant to oxidative stress than non-lipofuscin-laden ones may not be attributable to the lipofuscin per se but, rather, to the fact that one of the groups had been conditioned by exposure to an elevated concentration of oxygen. No control experiments were done to rule out this objection, and in the absence of such controls it is not possible to draw the conclusions made in the paper (Stroikin et al. 2007). Given that the consequences of lipofuscin accumulation are potentially important for our understanding of the mechanisms behind postmitotic ageing, solid experimental data on these matters are needed. Therefore, it would be most interesting if the authors repeated their experiments with correctly matched controls. For example, cells moved from 8% to 40% oxygen for a few days before starvation would be preconditioned to the ensuing stress without becoming significantly more lipofuscin-laden. U. T. Brunk (&) Division of Pharmacology, Faculty of Health Sciences, Linkoping University, Linkoping 581 85, Sweden e-mail: ulf.brunk@imv.liu.se
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