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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.
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.
The heart is an organ with high energy demands and metabolic flexibility, thus allowing for various energy substrates for ATP production under different physiological conditions. Zhang et al., Fernandez-Caggiano et al. and McCommis et al. converge on the mitochondrial pyruvate transporter as a key metabolic hub for the maintenance of cardiac metabolism and a critical determinant of cardiac metabolic plasticity during heart failure.
Cellular metabolism has emerged as a major biological node governing cellular behaviour. In their review, Boon et al. explore the mechanisms that maintain nuclear metabolic compartmentalization and the regulation of epigenetics, cell fate and cell physiology by nuclear metabolism.
A recent study by Karunakaran et al. suggests that RIPK1 is important in obesity and related metabolic traits. With genetic variation associated with expression and the risk of obesity, and repression of activity leading to a favourable metabolic profile in an obesogenic model, is there evidence for a potential therapeutic role?
Franco et al, review how metabolic insufficiency and prolonged stress responses impact signaling cascades and epigenetic reprogramming to lock T cells into an exhausted state.
Aberrant upregulation of de novo lipogenesis is linked to non-alcoholic fatty liver disease and some cancers. A new study by Kelly et al. finds that inhibiting this pathway by blocking the activity of acetyl-CoA carboxylase has unexpected effects on the formation of platelets from megakaryocytes within the bone marrow of primates but not rodents, thus suggesting clinical implications for de novo lipogenesis inhibitors as a new class of therapeutics.
Exercise is a powerful modifier of organismal, tissue and cellular metabolism. In their Review, Koelwyn et al. highlight how exercise-induced alterations in the tumour microenvironment can affect immunometabolic mechanisms and how these changes may contribute to the benefits of exercise on cancer initiation and progression.
Kusuyama et al. review the effects of maternal and paternal exercise on offspring metabolic health in adulthood, the time of life when metabolic diseases typically surface.
Islet of Langerhans transplantation as a cell therapy for type 1 diabetes faces obstacles that have prevented full and lasting engraftment in the liver, the currently preferred implantation site in clinical practice. Yu and colleagues circumvent these issues and achieve stable diabetes reversal by transplanting islets encapsulated in a simple collagen-based matrix into the more accessible subcutaneous space.
In this instalment of Career pathways, we hear from Anja Zeigerer and Myriam Aouadi about how the support of institutions, labs and families can galvanize scientists’ passion and productivity.
Cancer cells require exogenous cysteine for proliferation and survival. In this issue of Nature Metabolism, Zhang et al. demonstrate that deletion of 5-methylthioadenosine phosphorylase promotes the synthesis of polyamines from methionine, thereby conferring sensitivity to cysteine starvation.
Cellular metabolic demand skyrockets during intense exercise, thus rendering the communication of metabolic state essential for organismal homeostasis. Murphy, Watt and Febbraio discuss the physiological processes governing intertissue communication during exercise and the molecules mediating such cross-talk.
Hargreaves and Spriet review regulatory mechanisms of ATP resynthesis during exercise and summarize nutritional interventions that target muscle metabolism to enhance athletic performance.
The mechanistic target of rapamycin complex 1 (mTORC1) network integrates nutrient and energy signals that regulate metabolism and cell growth. Orozco et al. now show that the glycolytic intermediate dihydroxyacetone phosphate (DHAP) relays glycolytic activity to mTORC1 signalling.
GABA-expressing neurons in the arcuate nucleus of the hypothalamus regulate obesity in mice. A recent study indicates the importance of unexamined cell types.
AMPK is a crucial sensor of the cellular energetic state and is also activated during glucose starvation. A new study reports that AMP-activated protein kinase (AMPK) is activated by interaction with long-chain fatty acyl–CoA esters, which appear to be the long-sought endogenous AMPK ligands that bind the allosteric drug and metabolite (ADaM) site.
Zhang et al. discuss insights into the genetics of extreme human longevity and how genetics knowledge can be harnessed to guide the development of new therapies to extend human healthspan.
Diet and exercise are the two pillars of a healthful lifestyle for stemming the rising tide of metabolic disease. A new study in this issue reveals that the health benefits of diet and aerobic exercise are more interdependent than previously appreciated, thus reinforcing the importance of a holistic approach to maintaining a healthful lifestyle.
