The effect of obesity and aging on NAD+/Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue of monozygotic twin pairs discordant for BMI
Authors' conclusion
Impaired NAD+/SIRT metabolism in AT may play a key role in obesity- and aging-related diseases. Both conditions are characterized by downregulation of NAD+/SIRT pathway genes, correlating with increased adiposity, insulin resistance, inflammation, and dyslipidemia. Obesity uniquely disrupts expression of NAD+/SIRT regulated mitochondrial genes, while aging is characterized by altered PARP expression, particularly increased PARP1, likely exacerbating metabolic dysfunction in AT.
Study context
- Population
- Monozygotic twin pairs discordant for BMI (within-pair difference in BMI ≥ 2.5 kg/m²), aged 22–38 and 56–69 years; subcutaneous adipose tissue (AT)
- Participants
- 49 twin pairs
- Exposure
- Heavier vs leaner co-twins; older vs younger twin pairs
- Outcome
- NAD+/SIRT pathway gene expression in subcutaneous AT
Methodological detailsco-twin control design, RNA sequencing, DNA methylation analyses, linear mixed models
- Co-twin control design
- RNA sequencing
- DNA methylation analyses
- Linear mixed models
Main finding
As reported in the abstract
- SIRT5 and NAD+ biosynthetic genes downregulated in AT in both obesity and aging
- Obesity: downregulation of AT NAD+/SIRT genes and NAD+/SIRT regulated mitochondrial oxidative metabolism genes; upregulation of stress markers
- Aging: downregulation of AT PARPs, except upregulation of PARP1
- Mitochondrial metabolism and glycolysis genes linked to corresponding DNA methylation
- Downregulation of NAD+/SIRT genes correlated with increased adiposity, insulin resistance, inflammation and dyslipidemia
Observational data: associations, not effects.
Original publication
The effect of obesity and aging on NAD+/Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue of monozygotic twin pairs discordant for BMI. Int J Obes (Lond). Published 5 January 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →