Reviews & Analysis

The year 2022 has been notable for game-changing early progress in clinical trials with stem cell islets; durable and promising 20-year data with long-term outcomes in clinical islet transplantation; and the development of locally protective or gene-editing-based approaches to avoid long-term immunosuppression.

Calorie restriction and timed dietary intake are two approaches known to increase lifespan or delay age-associated diseases. New studies reveal the importance of the ‘how much’ and ‘when’ of dietary intake in ageing modulation and collectively demonstrate how protection of the internal clock by diet can delay the ageing process.

Adipose tissue is highly versatile, dynamic and essential for metabolic health. In 2022, several exciting discoveries provided a high-resolution view of cellular composition and cell–cell communication within the adipose niche, and revealed how adipose tissue communicates with other organs and modulates metabolism during normal and pathophysiological states.

In 2022, the activation mechanism of TSH receptor (TSHR) by TSH and autoantibodies was demonstrated, monocarboxylate transporter 8 (MCT8) deficiency was corrected with gene therapy in mice and mutant thyroid hormone receptor α (TRα) was activated with a synthetic ligand. These results offer translational perspectives for patients with common and rare diseases affecting these proteins.

Glucagon-like peptide 1 (GLP1) analogues are licensed options for obesity, but new treatments are required to obtain better weight loss and to directly address other co-morbidities, such as non-alcoholic fatty liver disease. Research published in 2022 shows that co-agonist combinations of GLP1 with other hormones provide clinically important advances.