Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol
Article first published online: 16 NOV 2011
© 2011 John Wiley & Sons A/S
Journal of Pineal Research
Volume 52, Issue 3, pages 271–281, April 2012
How to Cite
Cristòfol, R., Porquet, D., Corpas, R., Coto-Montes, A., Serret, J., Camins, A., Pallàs, M. and Sanfeliu, C. (2012), Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. Journal of Pineal Research, 52: 271–281. doi: 10.1111/j.1600-079X.2011.00939.x
- Issue published online: 20 MAR 2012
- Article first published online: 16 NOV 2011
- Accepted manuscript online: 21 OCT 2011 01:58PM EST
- Received September 7, 2011; Accepted October 17, 2011.
- aging brain;
- SAMP8 mouse neuron cultures;
- sirtuin 1
Abstract: The senescence-accelerated prone 8 (SAMP8) mouse strain shows early cognitive loss that mimics the deterioration of learning and memory in the elderly and is widely used as an animal model of aging. SAMP8 mouse brain suffers oxidative stress, as well as tau- and amyloid-related pathology. Mitochondrial dysfunction and the subsequent increase in cellular oxidative stress are central to the aging processes of the organism. Here, we examined the mitochondrial status of neocortical neurons cultured from SAMP8 and senescence-accelerated-resistant (SAMR1) mice. SAMP8 mouse mitochondria showed a reduced membrane potential and higher vulnerability to inhibitors and uncouplers than SAMR1 mitochondria. dl-buthionine-[S,R]-sulfoximine (BSO) caused greater oxidative damage in neurons from SAMP8 mice than in those from SAMR1 mice. This increased vulnerability, indicative of frailty-associated senescence, was protected by the anti-aging agents melatonin and resveratrol. The sirtuin 1 inhibitor, sirtinol, demonstrated that the neuroprotection against BSO was partially mediated by increased sirtuin 1 expression. Melatonin, like resveratrol, enhanced sirtuin 1 expression in neuron cultures of SAMR1 and SAMP8 mice. Therefore, a deficiency in the neuroprotection and longevity of the sirtuin 1 pathway in SAMP8 neurons may contribute to the early age-related brain damage in these mice. This supports the therapeutic use of sirtuin 1-enhancing agents against age-related nerve cell dysfunction and brain frailty.