Multiple pathways of SIRT6 at the crossroads in the control of longevity, cancer, and cardiovascular diseases.
Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD+-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite functional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast member, silent information regulator-2 (Sir2), and modulates genome stability, telomere integrity, transcription, and DNA repair. Its deficiency is associated with chronic inflammation, diabetes, cardiac hypertrophy, obesity, liver dysfunction, muscle/adipocyte disorders, and cancer. Besides, pieces of evidence showed that SIRT6 is a promoter of specific oncogenic pathways, thus disclosing its dual role regarding cancer development. Collectively, these findings suggest that multiple mechanisms, to date not entirely known, underlie the intriguing roles of SIRT6. Here we provide an overview of the current molecular mechanisms through which SIRT6 controls cancer and heart diseases, and describe its recent implications in the atherosclerotic plaque development.
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Milena
M
Vitiello
Department of Sciences and Technologies, University of Sannio, Benevento, Italy; CEINGE-Advanced Biotechnologies, Naples, Italy.
Alberto
A
Zullo
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Luigi
L
Servillo
Department of Sciences and Technologies, University of Sannio, Benevento, Italy.
Francesco Paolo
FP
Mancini
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Adriana
A
Borriello
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Alfonso
A
Giovane
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Fulvio
F
Della Ragione
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
Nunzia
N
D'Onofrio
Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. Electronic address: marialuisa.balestrieri@unina2.it.
Maria Luisa
ML
Balestrieri
D002318:Cardiovascular Diseases / Q000378:metabolism*; D004260:DNA Repair / Q000502:physiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008136:Longevity / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism*; D037761:Sirtuins / Q000378:metabolism*; D059505:Telomere Homeostasis / Q000502:physiology
C516592:SIRT6 protein, human; D037761:Sirtuins
Aging; Atherosclerosis; Cancer; Cardiovascular disease; Lifespan; SIRT6