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Title: CLOCK gene polymorphisms and quality of aging in a cohort of nonagenarians - the MUGELLO study

Author
item PAGLIAI, GIUDITTA - University Of Florence
item SOFI, FRANCESCO - University Of Florence
item DINU, MONICA - University Of Florence
item STICCHI, ELENA - University Of Florence
item VANNETTI, FEDERICA - The Don Carlo Gnocchi Foundation, Onlus (FDG)
item MOLINO LOVA, RAFFAELE - The Don Carlo Gnocchi Foundation, Onlus (FDG)
item ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item GORI, ANA - University Of Florence
item MARCUCCI, ROSSELLA - University Of Florence
item GIUSTI, BETTI - University Of Florence
item MACCHI, CLAUDIO - The Don Carlo Gnocchi Foundation, Onlus (FDG)

Submitted to: Scientific Reports
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/23/2018
Publication Date: 2/6/2019
Citation: Pagliai, G., Sofi, F., Dinu, M., Sticchi, E., Vannetti, F., Molino Lova, R., Ordovas, J.M., Gori, A.M., Marcucci, R., Giusti, B., Macchi, C. 2019. CLOCK gene polymorphisms and quality of aging in a cohort of nonagenarians - the MUGELLO study. Scientific Reports. 9(1):1472. https://doi.org/10.1038/s41598-018-37992-8.
DOI: https://doi.org/10.1038/s41598-018-37992-8

Interpretive Summary: The aging process is associated with sleep and circadian rhythm disturbances. This is essentially due to reduced day/night contrast, decreased sensitivity to light, napping, and a more sedentary lifestyle. Thus, this study aimed to investigate if genetic factors associated with the circadian control, could be related to successful aging. For this purpose, 356 elderly subjects (age range 88-106 years), mainly women were genotyped for three polymorphisms of the CLOCK gene in order to find associations with quality of aging. Our results show that genetic variation at the CLOCK gene was associated with quality of aging, assessed by the presence of overweight, hypertriglyceridemia, hyperglycemia, and hypercholesterolemia, as well as measures of sleep and depression, in a cohort of nonagenarians. These results reinforce the importance of the relationship between biological rhythms and healthy aging.

Technical Abstract: A total of 356 elderly subjects [257F; 88-106 years] were genotyped for three polymorphisms of the CLOCK gene by TaqMan real-time PCR approach, in order to find associations with quality of aging. Subjects homozygous for the minor allele of rs1801260 were less frequently overweight (p = 0.046), had higher fasting glucose levels (p=0.037), better scores at the Clock Drawing Test (CDT) (p=0.047) and worse scores at the Geriatric Depression Scale (p=0.032). Subjects homozygous for the minor allele of rs11932595 showed higher fasting glucose levels (p=0.044) and better scores at CDT (p=0.030). Conversely, subjects homozygous for the minor allele of rs4580704 showed higher triglyceride (p=0.012), and LDL-cholesterol levels (p=0.44), and a greater adherence to the Mediterranean diet (MD) (p=0.044). In addition, AAC, AAG, GGC and AGC (rs1801260-rs11932595-rs4580704) haplotypes were analyzed: AAG was associated with higher risk of overweight (p=0.008), hypertriglyceridemia (p=0.040) and hypercholesterolemia (p=0.036); GGC with lower risk of hyperglycemia (p=0.022), better sleep pattern (p=0.001) and with better score at mini-mental state examination (p=0.010); AGC with lower risk of depression (p=0.026) and AAC with lower adherence to the MD (p=0.028). Therefore, CLOCK gene polymorphisms let us hypothesize an involvement in the quality of aging in a cohort of nonagenarians.