Mitochondrial dysfunction and cellsenescence – skin deep into mammalian aging

Mitochondrial dysfunction and cellsenescence – skin deep into mammalian aging

There is a lively discussion going on as to whether oxidative stress is or is not a cause of (accelerated) aging, fuelled to a significant extent by the finding from Arlan Richardson’s group that mice heterozygous for the mitochondrial superoxide dismutase SOD2 showed increased oxidative stress, increased cancer incidence but not accelerated ageing [1]. A new twist to this story was introduced recently when it was shown that connective tissue-specific SOD2 knockouts developed multiple signs of progeria including short lifespan, associated with up-regulation of the cell senescence marker p16INK4A [2]. Mitochondrially generated oxidative stress is both an established cause [3] and a relevant consequence [4] of cell senescence, frequencies of senescent cells in connective tissue increase during mice aging [5], and destruction of senescent cells can ‘cure’ some age-related tissue dysfunction [6]. A paper by Judith Campisi’s and Simon Melov’s groups recently published in Aging [7] now further explores the connection between oxidative stress, cell senescence and aging. The authors demonstrate that mitochondrial dysfunction occurs in the epidermis of old (2 years) mice, measured as decreased complex II activity, and correlate this with increased senescence (shown by SAbGAL activity) in the stratum corneum. Moreover, they observe the same senescence phenotype in skin from young (17 – 20 days old) constitutive SOD2-/- mice, which were treated with the synthetic SOD and catalase mimetic EUK-189 in order to allow sufficient development to take place for a skin phenotype to develop. An increase of various senescence markers in the epidermis, the stratum corneum or the lining of the hair follicles was associated with epidermal thinning (a classical aging marker in skin) and increased expression of a keratinocyte terminal differentiation marker [7]. These data enforce two central hypotheses in the field, namely that of mitochondrial dysfunction as a cause of cell senescence, and of cell senescence as a relevant contributor to mammalian aging in vivo. 

impact factor of oncotarget Zoya Demidenko Dr. Zoya N. Demidenko Zoya N. Demidenko , Ph.D. is Executive Manager of the Oncotarget journal . Oncotarget publishes high-impact research papers of general interest and outstanding significance and novelty in all areas of biology and medicine: in translational, basic and clinical research including but not limited to cancer research, oncogenes, oncoproteins and tumor suppressors, signaling pathways as potential targets for therapeutic intervention, shared targets in different diseases (cancer, benign tumors, atherosclerosis, eukaryotic infections, metabolic syndrome and other age-related diseases), chemotherapy, and new therapeutic strategies. After earning her Ph.D. in molecular biology, Zoya was awarded a Fogarty post-doctoral Fellowship from the National Institutes of Health in Bethesda, MD. After successful completion of post-doctoral training, she continued her professional career at George Washington University and Albert Einstein School of Medicine . In 2005 she cofounded the startup company Oncotarget Inc. which is focused on the development of anti-aging and anti-cancer drugs. Her research interests include signal transduction, cell cycle and cellular senescence, and their pharmacological targeting. In 2009 she cofounded the publishing house Impact Journals which specializes in publishing scientific journals. In 2011 she was selected to be a Member of the National Association of Professional Women .

https://www.ncbi.nlm.nih.gov/pubmed/22228887