bims-resufa 2018-06-17 papers

Issue of 2018‒06‒17
two papers selected by
Vera Strogolova
Marquette University

Aging (Albany NY). 2018 Jun 10.

Mitochondrial peptides modulate mitochondrial function during cellular senescence.

Su-Jeong Kim, Hemal H Mehta, Junxiang Wan, Chisaka Kuehnemann, Jingcheng Chen, Ji-Fan Hu, Andrew R Hoffman, Pinchas Cohen.

Cellular senescence is a complex cell fate response that is thought to underlie several age-related pathologies. Despite a loss of proliferative potential, senescent cells are metabolically active and produce energy-consuming effectors, including senescence-associated secretory phenotypes (SASPs). Mitochondria play crucial roles in energy production and cellular signaling, but the key features of mitochondrial physiology and particularly of mitochondria-derived peptides (MDPs), remain underexplored in senescence responses. Here, we used primary human fibroblasts made senescent by replicative exhaustion, doxorubicin or hydrogen peroxide treatment, and examined the number of mitochondria and the levels of mitochondrial respiration, mitochondrial DNA methylation and the mitochondria-encoded peptides humanin, MOTS-c, SHLP2 and SHLP6. Senescent cells showed increased numbers of mitochondria and higher levels of mitochondrial respiration, variable changes in mitochondrial DNA methylation, and elevated levels of humanin and MOTS-c. Humanin and MOTS-c administration modestly increased mitochondrial respiration and selected components of the SASP in doxorubicin-induced senescent cells partially via JAK pathway. Targeting metabolism in senescence cells is an important strategy to reduce SASP production for eliminating the deleterious effects of senescence. These results provide insight into the role of MDPs in mitochondrial energetics and the production of SASP components by senescent cells.

Keywords: SASP (senescence-associated secretory phenotype); mitochondria; mitochondrial energetics; mitochondrial-derived peptides; mtDNA methylation; senescence

DOI: https://doi.org/10.18632/aging.101463

Comp Biochem Physiol A Mol Integr Physiol. 2018 Jun 06. pii: S1095-6433(18)30081-3. [Epub ahead of print]

Comparing Enchytraeus albidus populations from contrasting climatic environments suggest a link between cold tolerance and metabolic activity.

Anamarija Žagar, Martin Holmstrup, Tatjana Simčič, Barabara Debeljak, Stine Slotsbo.

Basal metabolic activity and freezing of body fluids create reactive oxygen species (ROS) in freeze-tolerant organisms. These sources of ROS can have an additive negative effect via oxidative stress. In cells, antioxidant systems are responsible for removing ROS in order to avoid damage due to oxidative stress. Relatively little is known about the importance of metabolic rate for the survival of freezing, despite a good understanding of several cold tolerance related physiological mechanisms. We hypothesized that low basal metabolism would be selected for in freeze-tolerant organisms where winter survival is important for fitness for two reasons. First, avoidance of the additive effect of ROS production from metabolism and freezing, and second, as an energy-saving mechanism under extended periods of freezing where the animal is metabolically active, but unable to feed. We used the terrestrial oligochaete, Enchytraeus albidus, which is widely distributed from Spain to the high Arctic and compared eight populations originating across a broad geographical and climatic gradient after they had been cold acclimated at 5 °C in a common garden experiment. Cold tolerance (lower lethal temperature: LT50) and the potential metabolic activity (PMA, an estimator of the maximal enzymatic potential of the mitochondrial respiration chain) of eight populations were positively correlated amongst each other and correlated negatively with latitude and positively with average yearly temperature and the average temperature of the coldest month. These results indicate that low PMA in cold tolerant populations is important for survival in extremely cold environments.

Keywords: Cold adaptation; Enchytraeus albidus; Invertebrates; LT50; Latitude; Macro-ecology; Metabolic potential; Metabolism

DOI: https://doi.org/10.1016/j.cbpa.2018.05.020