The improvement of neuronal function in normal aging by melatonin is mediated by altering mitochondria bioenergetics (1009.3)

The changes in mitochondria bioenergetics play a critical role in neuronal function with age. Mitochondria from synaptosomes in the cerebral cortex of young (6 months), middle‐age (13 months) and old (26months) mice were isolated and transferred to mitochondria DNA‐less LL/2‐m21 cell line (rho‐zero) to generate cybrids. Mitochondria bioenergetics studies of the cybrids show that there was significant reduction with age in mitochondria membrane potential (MMP), P<0.05, in the young, middle‐aged and old synaptosomal mitochondria bearing cybrids respectively. Adenosine triphosphate (ATP) levels were also significantly lower in the old mitochondria bearing cybrids compared with middle age and young cybrids (P<0.05). Melatonin pre‐treatment at a concentration of 1mM in glucose replaced with galactose medium containing 1mM melatonin after 6 hours significantly improved cell viability and restored MMP in the old mitochondria bearing cybrids , S‐O‐48 (P<0.05). Furthermore, melatonin treatment in young mitochondria bearing cybrids, S‐Y‐24 lowered MMP (P<0.05) and increased MMP in middle aged mitochondrial bearing cybrid S‐M‐29 (P<0.05) in galactose medium. In the young cybrids, there was no significant difference in ATP levels between the melatonin treated cybrids and cybrids without treatment (P>0.05). The young mitochondria bearing cybrids were able to produce ATP optimally in the galactose medium which shows they have functional mitochondria. ATP was significantly increased in the middle‐aged mitochondria cybrid, S‐M‐29, and old mitochondria bearing cybrids, S‐O‐48, with melatonin treatment. These results establish a strong relationship between melatonin and mitochondria bioenergetics. It also gives support to other evidences that melatonin may be a potential therapeutic mitochondria target in aging.