Volume 1 Issue 10, October 2019

Nuclear DNA damage has detrimental effects on cellular homoeostasis and accelerates the ageing process. A new study causally links error-prone mitochondrial replication to increased nuclear DNA damage, thus suggesting that the hallmarks of ageing are associated with nuclear genome instability, a potential unifying denominator in the ageing process.

Findeisen et al. have engineered IC7Fc, a cytokine for the treatment of type 2 diabetes, that selectively activates beneficial metabolic pathways systemically and in metabolic tissues without promoting an inflammatory response.

GDF15 is an anorectic hormone that signals organismal stress to the brain. New data suggest that GDF15 enhances tolerance to acute inflammation by modulating liver lipid metabolism and triglyceride availability in mice.

Falkenberg et al. summarise major metabolic pathways operating in endothelial cells, discuss their roles in the growth and function of blood and lymph vessels, and highlight therapeutic opportunities that arise from targeting endothelial cell metabolism.

The authors of this Review present a framework for understanding fundamental principles of metabolic regulation, drawing analogies between metabolic control and economic theory to discuss supply- and demand-driven metabolism.

Increased mitochondrial DNA (mtDNA) replication frequency is shown to lead to defects in maintenance of the nuclear genome due to reallocation of nucleotides to mitochondria, challenging the proposed direct role of mtDNA mutations as drivers of cellular and organismal ageing in mammalian progerias.

The cellular effects of cold preservation in heart transplantation and how warm ischaemia leads to damage are unclear. Here the authors identify succinate accumulation as a major damaging metabolic change in warm ischaemia.

Here the authors provide a regulatory framework for the cardiac mitochondrial ATP synthase, which is shown to be dependent on cellular activity; levels of Ca²⁺, ADP and NADH; and the potential of the inner mitochondrial membrane.

After development, adult skeletal muscle retains the capacity to regenerate by activating muscle stem cells. Here the authors demonstrate that the glycosylphosphatidylinositol-anchored membrane protein GAS1, which is induced in muscle stem cells with age, suppresses muscle regenerative capacity but can be inhibited by glial cell line-derived neurotrophic factor (GDNF).

Anoxia─lack of oxygen─commonly occurs during ischaemic heart disease. Using yeast, worms and mice, Hannich et al. show that anoxia-associated tissue injury and cell death are due to accumulation of a non-canonical sphingolipid, 1-deoxydihydroceramide, that damages the cytoskeleton.

Non-alcoholic steatohepatitis (NASH) is characterized by lipid accumulation within hepatocytes and fibrosis. Seitz et al. show that the GTPase protein Rab24 is increased in the livers of people who are obese or have NASH.