Transcriptome-Wide Insights: Neonatal Lactose Intolerance Promotes Telomere Damage, Senescence, and Cardiomyopathy in...

Area of Science:

• Cardiovascular Biology
• Neonatal Development
• Aging Research

Background:

• Cardiovascular diseases (CVD) are a leading cause of global mortality, linked to aging and neonatal development.
• Adverse neonatal conditions can disrupt cardiomyocyte differentiation, leading to heart dysfunction.
• Neonatal lactose intolerance (NLI) is a potential neonatal stressor impacting long-term cardiac health.

Purpose of the Study:

• To investigate the long-term effects of NLI-induced inflammatory and oxidative stress on cardiomyocyte transcriptome and phenotype.
• To evaluate the impact of NLI on cardiomyocyte ploidy, telomere integrity, and cardiac function.
• To assess the correlation between NLI and accelerated aging, cardiac dysfunction, and survival rates.

Main Methods:

• Cytophotometric and morphologic analysis of left ventricle (LV) cardiomyocytes.
• Transcriptomic profiling of LV cardiomyocytes.
• Echocardiography to assess cardiac structure and function.
• Survival rate estimation.

Main Results:

• NLI induced hyperpolyploidy and telomere fusion in LV cardiomyocytes.
• Transcriptomic analysis revealed accelerated aging, telomere damage, and chromatin decompaction.
• Suppression of muscle contraction and energy metabolism pathways observed.
• Echocardiography showed significant LV dilation and reduced ejection fraction.
• NLI shortened median lifespan by approximately 18%.

Conclusions:

• NLI accelerates cardiac aging through oxidative stress and telomere DNA damage, leading to hyperpolyploidization and impaired cardiac function.
• Neonatal inflammatory and metabolic stressors like NLI increase susceptibility to cardiovascular diseases.
• Early identification and management of NLI are vital for mitigating long-term cardiovascular risks.