bims-ciryme 2026-05-17 papers

Annu Rev Nutr. 2026 May 11.

Circadian Alignment Through Time-Restricted Feeding: Implications for Health and Longevity.

Samantha E Iiams, Nathan J Skinner, Carla B Green, Joseph S Takahashi.

Time-restricted feeding (TRF), which confines food intake to a defined daily window, has emerged as a promising nonpharmacological strategy to improve health by aligning behavior and physiology with the endogenous circadian clock. Preclinical research has expanded substantially, now spanning both nocturnal and diurnal species, diverse dietary regimens, varying intervention durations, and examinations of sex-specific responses. These consistently show that synchronizing feeding-fasting cycles with the natural active phase of an organism's circadian rhythm enhances rhythmic gene expression across tissues. Concomitantly, this mitigates metabolic dysfunction, reduces inflammation, and lowers disease risk, often without reducing caloric intake. While findings in animal models are robust, human outcomes have been more modest and variable, influenced by the timing and duration of feeding window, metabolic state, and sex. This review synthesizes current insights into the relationship between TRF and circadian rhythms, highlighting recent discoveries and the challenges that remain for translation to humans.

DOI: https://doi.org/10.1146/annurev-nutr-112525-011241

Diabetologia. 2026 May 12.

Nocturnal fat oxidation is lower in older individuals with overweight/obesity, including those with type 2 diabetes, and is associated with fasting triglyceride levels.

Soraya S de Kam, Jeroen H P M van der Velde, Anna Veelen, Johanna A Jörgensen, Joris Hoeks, Patrick Schrauwen.

AIMS/HYPOTHESIS: We previously showed that nocturnal fat oxidation is reduced in older individuals with overweight/obesity and impaired glucose tolerance and insulin sensitivity compared with young lean individuals. Here, we compared nocturnal energy expenditure and substrate oxidation across groups varying in age, body composition and metabolic status to unravel factors underlying variations in nocturnal substrate metabolism.
METHODS: Data were collected from 18 previously conducted human clinical studies (N=187), all performed under conditions of energy balance with similar diet composition and meal timing. Individuals were categorised into four groups: young lean (YL); older lean (OL); older with overweight/obesity (OBE); and older with overweight/obesity and type 2 diabetes (T2D). Nocturnal energy expenditure and substrate oxidation were determined by whole-room indirect calorimetry, body composition was assessed by air-displacement plethysmography or dual energy x-ray absorptiometry, and glucose, insulin, HOMA-IR, NEFA and triglycerides were measured from fasted blood samples. Group comparisons for nocturnal energy expenditure and substrate oxidation were performed using Kruskal-Wallis tests, and over time using linear mixed models including group × time interactions, with Bonferroni correction applied to both analyses. Multivariate linear regression analysis was applied to identify whether age, sex, HOMA-IR, fasting NEFA, fasting triglycerides, fat mass and fat-free mass were independent factors of nocturnal energy expenditure and substrate oxidation.
RESULTS: Nocturnal energy expenditure, adjusted for fat-free mass, was higher in OBE compared with YL and OL (p<0.01 for both); it was also higher in T2D compared with OL (p<0.01). Nocturnal fat oxidation, expressed as a percentage of energy expenditure, was lower in OBE (median: 46.28%, IQR: 37.74-53.05) and T2D (median: 46.48%, IQR: 41.05-53.65) compared with YL (median: 52.95%, IQR: 47.82-57.61; p<0.01 for both) and OL (median: 55.21%, IQR: 54.15-58.89; p<0.01 for both). Standardised linear regression models revealed that fasting triglycerides were positively associated with nocturnal respiratory exchange ratio (β=0.337; 95% CI 0.165, 0.508) and nocturnal carbohydrate oxidation (% of energy expenditure; β=0.337; 95% CI 0.166, 0.509), and inversely associated with nocturnal fat oxidation (% of energy expenditure; β=-0.352; 95% CI -0.520, -0.813).
CONCLUSIONS/INTERPRETATION: Nocturnal fat oxidation (% of energy expenditure) is diminished in older individuals with overweight/obesity, irrespective of diabetes status. No differences in nocturnal energy expenditure (adjusted for fat-free mass) or substrate oxidation were observed between young and older lean individuals, suggesting that age per se may not strongly influence nocturnal substrate metabolism. Fasting triglyceride level was the strongest associated factor of nocturnal substrate oxidation.

Keywords: Energy expenditure; Indirect calorimetry; Metabolic flexibility; Nocturnal fat oxidation; Obesity; Substrate metabolism; Type 2 diabetes

DOI: https://doi.org/10.1007/s00125-026-06736-z

Nat Rev Genet. 2026 May 14.

Time matters: circadian genetics and the molecular logic of human health and disease.

Tia Tyrsett Kuo, Jiarui Wang, Steve A Kay.

Time is an essential but often underappreciated determinant of human physiology and disease. The circadian clock, a genetic timing system, orchestrates transcriptional and signalling networks across tissues to maintain homeostasis. Recent discoveries have refined our understanding of this system, from a linear transcription-translation feedback loop to a distributed, dynamically coupled network that integrates environmental cues and physiological processes. Genetic variation in core circadian genes and circadian misalignment are now recognized as key modifiers of disease risk, progression and therapeutic response. As precision medicine begins to embrace temporal biology, defining how the circadian clock operates in health and disease has become increasingly important. This Review synthesizes recent advances in circadian genetics and molecular mechanisms, emphasizing their physiological, pathological and therapeutic implications, and outlines future priorities: resolving the composition of the molecular clock, developing disease-specific models, and expanding the chemical toolbox to modulate and interrogate circadian pathways.

DOI: https://doi.org/10.1038/s41576-026-00962-2