- Inflammaging, metabolic syndrome and melatonin: a call for treatment studies

HARDELAND R; CARDINALI DP

NEUROENDOCRINOLOGY

KARGER

Lugar: Basel; Año: 2017 vol. 104 p. 382 - 397

0028-3835

The metabolic syndrome (MS) is acollection of risk factors for cardiovascular disease, including obesity,hypertension, hyperinsulinemia, glucose intolerance and dyslipidemia. MS isassociated with low-grade inflammation of the white adipose tissue, which cansubsequently lead to insulin resistance, impaired glucose tolerance anddiabetes. Adipocytes secrete proinflammatory cytokines as well as leptin andtrigger a vicious circle which leads to additional weight gain largely as fat.The imbalance between inflammatory and anti-inflammatory signals is crucial toaging. Healthy aging can benefit from melatonin, a compound known to possessdirect and indirect antioxidant properties, to have a significant protectiveeffect on mitochondrial function, to enhance circadian rhythm amplitudes, tomodulate the immune system and to exhibit neuroprotective actions. Melatoninlevels decrease in the course of senescence and are more strongly reduced indiseases related to insulin resistance. This short review article analyzes themultiple protective actions of melatonin that are relevant to the attenuationof inflammatory responses and progression of inflammaging and how melatonin iseffective to curtail MS in animal models of hyperadiposity. The clinical datasupporting the possible therapeutic use of melatonin in human MS are alsoreviewed. Since attention has been focused on the development of potent melatoninanalogs with prolonged effects (ramelteon, agomelatine, tasimelteon,piromelatine) and in clinical trials these analogs were administered in dosesconsiderably higher than those usually employed for melatonin, clinical trialson melatonin in the range of 50-100 mg/day are needed to further assess itstherapeutic value in MS.