High Body Mass Index is Associated with Elevated Blood Levels of Progerin mRNA

Abstract

Obesity is a well-described risk factor resulting in premature aging of the cardiovascular system ultimately limiting longevity. Premature cardiac death and aging is the hallmark of Hutchinson–Gilford syndrome (HGPS), a disease caused by defined mutations in the lamin A gene leading to a shortened prelamin A protein known as progerin. Since small amounts of progerin are expressed in healthy individuals we aimed to investigate the association of Body-Mass-Index (BMI) with respect to expression of progerin mRNA in blood samples of patient with known cardiovascular disease. In this cross-sectional retrospective analysis, 111 patients were consecutively included of which 46 were normal (BMI < 25 kg/m2) and 65 overweight (BMI ≥ 25.0 kg/m2). Blood samples were analyzed for quantitative expression of progerin mRNA. Progerin as well as high-sensitive C-Reactive Protein (hs-CRP) levels were significantly upregulated in the overweight group. Linear regression analyses showed a significant positive correlation of BMI and progerin mRNA (n = 111; r = 0.265, p = 0.005), as well as for hs-CRP (n = 110; r = 0.300, p = 0.001) and for Hb1Ac (n = 110; r = 0.336, p = 0.0003). Our data suggest that BMI strongly correlates with progerin mRNA expression and inflammation. Progerin might contribute to well described accelerated biologic aging in obese individuals.

ZMPSTE24 Is Associated with Elevated Inflammation and Progerin mRNA

“…Since we previously also found a positive association between progerin mRNA, overweight (body mass index), and inflammation (hs-CRP) our data may suggest a positive link between cardiovascular aging and inflammation in patients with heart failure [ 10 ]. Increased progerin mRNA expression was related to LV dysfunction, and progerin expression in the nucleus of cardiomyocytes was related to apoptotic cell death in patients with dilative cardiomyopathy [ 9 ].…”

“…Diagnoses of heart failure etiology are depicted in Table A1 . Most of the patients suffered from DCM, followed by ICM, hypertrophic cardiomyopathy and other reasons for heart failure [ 10 ].…”

“… Summary of our previous and recent findings: In a heart failure outpatient cohort we found a positive correlation of the premature aging marker progerin with lamin A/C and ZMPSTE24 mRNA, which may link both markers also with cardiovascular aging. Moreover, chronic inflammation (CRP) was positively associated with increased expression levels of progerin [ 10 ], lamin A/C and ZMPSTE24 mRNA, providing a possible link of premature aging with inflammation. …”

“…Since laminopathies are a known cause of cardiomyopathies, we recently found a positive correlation between progerin mRNA expression and LV dysfunction in patients with dilated cardiomyopathy [ 9 ]. Furthermore, we previously found an association of obesity and inflammation (hs-CRP) with high levels of progerin mRNA expression [ 10 ].…”

Ranking Biomarkers of Aging by Citation Profiling and Effort Scoring

“…A recent study has shown that elevated blood levels of progerin can be detected in people with obesity, suggesting a cause for premature aging of the cardiovascular system. Therefore, progerin might be measured in blood samples and be adapted for diagnostic measurements (Messner et al, 2019). Another marker of cellular senescence, which can be investigated in cultured cells (e.g., based on punch skin biopsy), are senescent-associated histone foci (SAHF).…”