Age‐related increase of superoxide generation in the brains of mammals and birds

Abstract

SummaryOxidative stress, an imbalance between endogenous levels of oxygen radicals and antioxidative defense, increases with aging. However, it is not clear which of these two factors is the more critical. To clarify the production of oxygen radicals increases with age, we examined oxygen radical-dependent chemiluminescent signals in ex vivo brain slices using a novel photonic imaging method. The chemiluminescent intensity was significantly decreased by the membrane permeable superoxide dismutase (SOD)/catalase mimic, but not by Cu,Zn-SOD. Inhibitors for complex I, III, and IV of the mitochondrial electron transport chain transiently enhanced the chemiluminescent signal. The superoxide-dependent chemiluminescent intensity in senescence accelerated mouse (SAM) brain tissues increases with age. Moreover, the slope of the age-dependent increase was steeper in SAMP10, a strain characterized by a short lifespan and atrophy in the frontal cerebral cortex, than the senescenceresistant strain SAMR1, which has a longer lifespan. An increase in chemiluminescence with age was also observed in C57/BL6 mice, Wistar rats, and pigeons, although levels of chemiluminescence were lower in the pigeons than murines. The rate of age-related increases of superoxidedependent chemiluminescence was inversely related to the maximum lifespan of the animals. The activity of superoxide dismutase was unchanged during the aging process in the brain. This suggested that superoxide production itself may increase with age. We speculated that reactive oxygen may be a signal to determine the aging process.

Reversal of aging‐associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and NMDA receptor function

“…Recent studies indicate that there exist modulatory effects of redox status on synaptic plasticity (Colton et al, 1989;Pellmar et al, 1991;Avshalumov et al, 2000;Kamsler & Segal, 2003;Cai et al, 2008). Considering the alterations of redox status (Sandhu & Kaur, 2002;Zhu et al, 2006;Murali & Panneerselvam, 2007;Petrosillo et al, 2008;Sasaki et al, 2008) accompanied by the dysfunction of synaptic plasticity in aged animals, we propose that aging-related synaptic hypofunction might be at least partly because of the accumulation of oxidative damage and the decline in the activity of endogenous reduction system. Cysteine residues in some key proteins are involved in the crucial functional regulation of many key proteins, and they are the most susceptible targets of oxidative modulation; thus, more pronounced redox modifications of protein-bound thiols at key molecules involved in synaptic plasticity may occur with concomitant of brain aging.…”

The endocannabinoid system in normal and pathological brain ageing

“…Furthermore, as mentioned earlier, one of the largest class of genes upregulated in ageing are involved in oxidative defence and DNA repair [47,68]. Nevertheless, an increase in the amount of oxidized macromolecules in ageing is a generally observed phenomenon in a wide range of species [69,70]. Enhanced oxidative stress in the brain generally correlates with cognitive decline [46,71] and with an enhanced risk for the development of neurodegenerative diseases [72,73].…”

Mitochondria impairment correlates with increased sensitivity of aging RPE cells to oxidative stress

“…Mitochondrial decay is evident during normal aging of tissues as well and causes the cell's anti-stress pathways to operate with less efficiency [26][27][28]. Specifically, alterations in cytoplasmic Cu/Zn-superoxide dismutase (SOD), lipid peroxidation, mitochondrial Mn-SOD, and oxidative stress markers have been observed [27,28].…”

“…Specifically, alterations in cytoplasmic Cu/Zn-superoxide dismutase (SOD), lipid peroxidation, mitochondrial Mn-SOD, and oxidative stress markers have been observed [27,28]. Knockdown of the mitochondrial heat shock protein 70 promotes progerialike phenotypes in Caenorhabditis elegans implying a direct link between mitochondrial function and aging [29].…”