Bloom syndrome patients and mice display accelerated epigenetic aging.
Jamie LeeJoshua ZhangMaeve FlanaganJulian A MartinezChristopher M CunniffNicole KucineAke T LuAmin HaghaniJuozas GordevičiusSteve HorvathVivian Y ChangPublished in: Aging cell (2023)
Bloom syndrome (BSyn) is an autosomal recessive disorder caused by variants in the BLM gene, which is involved in genome stability. Patients with BSyn present with poor growth, sun sensitivity, mild immunodeficiency, diabetes, and increased risk of cancer, most commonly leukemias. Interestingly, patients with BSyn do not have other signs of premature aging such as early, progressive hair loss and cataracts. We set out to determine epigenetic age in BSyn, which can be a better predictor of health and disease over chronological age. Our results show for the first time that patients with BSyn have evidence of accelerated epigenetic aging across several measures in blood lymphocytes, as compared to carriers. Additionally, homozygous Blm mice exhibit accelerated methylation age in multiple tissues, including brain, blood, kidney, heart, and skin, according to the brain methylation clock. Overall, we find that Bloom syndrome is associated with accelerated epigenetic aging effects in multiple tissues and more generally a strong effect on CpG methylation levels.
Keyphrases
- dna methylation
- genome wide
- gene expression
- copy number
- end stage renal disease
- case report
- healthcare
- resting state
- type diabetes
- white matter
- heart failure
- ejection fraction
- multiple sclerosis
- chronic kidney disease
- high fat diet induced
- newly diagnosed
- cardiovascular disease
- public health
- mental health
- functional connectivity
- skeletal muscle
- atrial fibrillation
- young adults
- soft tissue
- cerebral ischemia
- transcription factor
- intellectual disability
- weight loss
- autism spectrum disorder
- risk assessment
- social media
- duchenne muscular dystrophy
- childhood cancer