Neuroprotective role of intermittent fasting in senescence-accelerated mice P8 (SAMP8)

M. Tajes (1, 2) , J. Gutierrez-Cuesta (1, 2) , J. Folch (2, 3) , D. Ortuño-Sahagun (4) , E. Verdaguer (1, 2) , A. Jiménez (1, 2) , F. Junyent (2, 3) , A. Lau (5) , A. Camins (1, 2) , M. Pallàs (1, 2)

1 Unitat de Farmacologia i Farmacognòsia Facultat de Farmàcia
2 CIBERNED - Centro de Investigacion Biomédica en Red sobre Enfermedades Neurodegenerativas
3 Facultat de Medicina i Ciències de la Salut
4 Departamento de Biología Celular y Molecular
5 Neurosciences Department

Dietary interventions have been proposed as way to increase lifespan and improve health. The senescence-accelerated prone 8 (SAMP8) mice have a shorter lifespan and show alterations in the central nervous system. Moreover, this mouse strain shows decreased sirtuin 1 protein expression and elevated expression of the acetylated targets NFκB and FoxO1, which are implicated in transcriptional control of key genes in cell proliferation and cell survival, in reference to control strain, SAMR1. After eight weeks of intermittent fasting, sirtuin 1 protein expression was recovered in SAMP8. This recovery was accompanied by a reduction in the two acetylated targets. Furthermore, SAMP8 showed a lower protein expression of BDNF and HSP70 while intermittent fasting re-established normal values. The activation of JNK and FoxO1 were also reduced in SAMP8 mice subjected to an IF regimen, compared with control SAMP8. Our findings provide new insights into the participation of sirtuin 1 in ageing and point to a potential novel application of this enzyme to prevent frailty due to ageing processes in the brain.

Mots clés: Ageing; neurodegeneration; NFκB; ADAM10; BDNF; sirtuin 1

M. Tajes, J. Gutierrez-Cuesta, J. Folch, D. Ortuño-Sahagun, E. Verdaguer, et al.. Neuroprotective role of intermittent fasting in senescence-accelerated mice P8 (SAMP8). Experimental Gerontology, 2010, 45 (9), pp.702. ⟨10.1016/j.exger.2010.04.010⟩. ⟨hal-00615111⟩