How UCP1 Changes with Age

How UCP1 Changes with Age

Uncoupling protein 1 (UCP1), also known as thermogenin, is a member of the mitochondrial anion carrier protein family. It is a 33 kDa protein encoded by the UCP1 gene in humans. UCP1 is localized to the inner mitochondrial membrane of brown adipocytes, where it uncouples oxidative phosphorylation from ATP synthesis to produce heat. The work on age-related changes in UCP1 centres on the adrenergic signalling pathway and its downstream effectors, particularly the β-adrenergic receptors and the TGF-β superfamily.

Age-related declines in UCP1 expression and brown adipose tissue (BAT) activity have been observed in rodents and humans, but the mechanisms are not fully defined. The evidence summarized here comes from animal models and in vitro systems; no human dosing or clinical recommendations are provided.

Research Studies

Follistatin and adipose browning in mice

Follistatin (FST) binds to and neutralizes members of the transforming growth factor-beta (TGF-β) superfamily, regulating skeletal muscle, adipose, and bone homeostasis. In mice, FST promotes adipose browning and enhances energy metabolism, leading to improved plasma lipid profiles. Transcriptomic and metabolomic analyses of the Hybrid Mouse Diversity Panel (HMDP) revealed that Fst expression was negatively correlated with aortic lesion area, suggesting a link between FST, BAT activation, and reduced atherosclerosis [1].

GDF-11 and cold-induced browning in mice

Growth differentiation factor 11 (GDF-11), a circulating member of the TGF-β superfamily, has been implicated in metabolic regulation. In mice exposed to cold, GDF-11 expression and SMAD2/3 activation were assessed in brown adipose tissue (BAT), visceral and subcutaneous white adipose tissue (WAT), and skeletal muscle. The study combined in vivo results with in vitro approaches using 3T3-L1 adipocytes [2].

Finerenone and adipose browning in humans

Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, has anti-inflammatory, antifibrotic, and metabolic effects. A clinical trial is investigating whether finerenone reduces atrial fibrillation recurrence after catheter ablation. Preclinical studies suggest finerenone promotes browning of adipose tissue and improves epicardial adipose tissue (EAT) characteristics [3]. This trial is ongoing and does not report UCP1-specific outcomes.

Exercise and diet effects on adipose tissue in humans

A study in middle-aged volunteers with metabolic syndrome is examining whether physical exercise and/or a Mediterranean diet preserve adipose tissue functionality and retard skeletal muscle aging. The study assesses mitochondrial biogenesis and accumulation of reactive oxygen species (ROS) [4]. UCP1 is not a primary endpoint.

Syringaresinol and skeletal muscle SIRT1-FNDC5/irisin axis in vitro

Syringaresinol (SYR), a plant-derived lignan, was tested in differentiated C2C12 myotubes to assess its effects on SIRT1-related FNDC5/Irisin signalling and high-fat diet-associated metabolic outcomes. The study used SIRT1 activator SRT1720 and inhibitor EX-527 to probe the pathway [5]. This is an in vitro study and does not directly measure UCP1.

Time-restricted feeding and HIIT in diabetic rats

A study in diabetic rats evaluated the independent and combined effects of time-restricted feeding (TRF) and high-intensity interval training (HIIT) on thermogenesis-related protein abundance in white adipose tissue (WAT). Forty male Wistar rats were divided into normal and diabetic groups [6]. UCP1 was among the thermogenesis-related proteins assessed.

β2-adrenergic receptor stimulation in human adipose-derived stem cells

β-Adrenergic receptors drive the induction of beige adipocytes in rodents and humans, but the dominant human subtype remains debated. This study aimed to confirm whether human adipose-derived mesenchymal stem cell (hADSC)-derived adipocytes can serve as a beiging-competent model under human-relevant conditions [7]. The findings are in vitro and do not address age-related changes.

Bombesin receptor-activated protein homolog deficiency in mice

Bombesin receptor-activated protein (BRAP) and its mouse homolog, BC004004, are expressed in the central nervous system. In feeding experiments, BRAP homolog knockout mice (BC004004^-/-) showed reduced preference for a high-fat diet and alleviated metabolic dysfunction [8]. This study does not directly measure UCP1.

Comparison of UCP1-related findings across models

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Sources

• [1] Follistatin Mitigates Atherosclerosis Through Activation of Arginine Metabolism and Adipose Browning
• [2] GDF-11 triggers cold-induced browning and metabolic activation of adipose tissue
• [3] Finerenone After Catheter Ablation to Reduce Atrial Fibrillation Recurrence
• [4] Beneficial Effects of Exercise and Healthy Diets on Muscle and Adipose Tissue
• [5] Syringaresinol activates the skeletal muscle SIRT1-FNDC5/irisin axis to enhance weight management
• [6] Effects of time-restricted feeding and high-intensity interval training on thermogenesis-related protein abundance in white adipose tissue of diabetic rats
• [7] β2-adrenergic receptor stimulation drives differentiation of human adipose-derived mesenchymal stem cells into beige adipocytes
• [8] Bombesin receptor-activated protein homolog deficiency reduces food intake and alleviates metabolic dysfunction in high-fat diet treated mice