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Telomere shortening in adipocyte progenitors, promoted by genetic Tert inactivation, is shown to compromise adipose tissue health and systemic metabolism, providing a possible mechanistic link between obesity, ageing and metabolic disease.
Martin-Perez et al. show that the beneficial effects of rapamycin in a mouse model of Leigh syndrome are associated with downregulation of protein kinase C.
Hibernation is a state of extreme metabolic and physiological plasticity occurring in conjunction with physical inactivity and prolonged fasting. Using in vivo tracing, Rice et al. reveal that nitrogen recycling staves off ammonia toxicity during hibernation in ground squirrels.
Osteoclasts are the body’s exclusive bone-resorbing cells; however, their differentiation trajectory remains unclear. Using single-cell RNA sequencing, Tsukasaki et al. provide a comprehensive road map of osteoclastogenesis, unveiling stepwise molecular events underlying osteoclast cell fate transitions.
A particularly aggressive subtype of lung cancer with mutations in KRAS and LKB1 is shown to depend on increased hexosamine biosynthesis mediated by the enzyme GFPT2.
By using single-cell transcriptomics, Weng et al. reveal complex temporal gene control during pancreatic beta-cell differentiation from human embryonic stem cells, allowing for the construction of a unique lineage tree and optimization of differentiation protocols.
Wei et al. identify the HDL receptor SR-B1 as a host factor that enhances infection of cultured cells with SARS-CoV-2 in the presence of ACE2, thus providing a possible molecular connection between lipoprotein metabolism and COVID-19.
UCP2 is shown in yeast and mammalian cells to transport aspartate out of mitochondria, thus enabling KRAS-mutated pancreatic ductal adenocarcinoma cells to perform glutaminolysis to support cancer growth.
Oncogenic transformation can render cancer cells dependent on aberrant expression of glycolytic enzyme isoforms. Lin et al. describe a novel enolase inhibitor, POMHEX, that can selectively kill ENO1-deleted glioblastomas.
The restoration of the progressive decline in nicotinamide adenine dinucleotide (NAD+) levels mitigates certain age-associated dysfunctions. A fundamental question is how the NAD+-consuming enzyme CD38 decreases NAD+ levels during ageing. Two new studies by Chini et al. and Covarrubias et al. in this issue of Nature Metabolism show that CD38 expression in macrophages induced by senescence-associated inflammation accounts for the age-related decline in NAD+ levels.
Chini et al. demonstrate that CD38+ expression in immune cells increases during aging, owing to the senescence-associated secretory phenotype of senescent cells, and the ecto-enzymatic activity of CD38+ affects intracellular NAD+ levels in vivo by hydrolyzing the NAD+ intermediate nicotinamide mononucleotide extracellularly.
Senescent cells in fat and liver are shown to attract M1-like macrophages with increased expression of the NAD-consuming enzyme CD38, leading to their local accumulation and providing a mechanism for the age-associated decline in tissue NAD+ levels.
The PI3K–PTEN signalling pathway is a central regulator of metabolic homeostasis. Brunner et al. find that cell-intrinsic PI3K signalling allows adipose tissue macrophages to buffer obesity-induced lipotoxicity by promoting lipid uptake and catabolism.
The nuclear factor kappa B subunit c-Rel acts as a master regulator of metabolism and signalling in epithelial cells and macrophages that drives inflammation and fibrogenesis in various models of fibrosis.
A new global measure of cell-to-cell transcriptional variability from single-cell RNA-sequencing data has been developed by Levy et al., on the basis of the transcriptional interrelations between genes. The new variable, termed global coordination level, decreases with age in different organisms and cell types and correlates with high mutational load in cells.
PDGFRβ+ perivascular mesenchymal cells are shown to regulate chronic adipose-tissue inflammation in obesity through downregulation of ZFP423, a transcriptional corepressor of NF-κB.