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Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Amyloid-ß-peptide (Aß) forms senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles, are the hallmarks of AD neuropathology. Evidence support the involvement of immune system in AD progression and current concepts regarding its pathogenesis include the participation of inflammatory and autoimmune components in the neurodegenerative process. Pathologically, immune system components have been detected in the brain, cerebrospinal fluid (CSF) and in serum of AD subjects and their trend of variation correlates with disease progression. However, patients with AD present significantly lower levels of antibody immunoreactivity against Aß in serum and CSF than healthy controls suggesting that a depletion of such patrolling system is involved in the deposition of toxic aggregates in AD. Within this frame, incomplete and often controversial results are reported about CNS immune/ autoimmune responses during AD, and a better comprehension of such processes is needed. Our research will aim to shed light on the nature and potential role of autoantibodies in CSF and serum from AD and amnestic mild cognitive impairment (aMCI) patients compared to healthy subjects by using an immunoproteomics approach. Our method allows recognition of natural occurring antibodies by the identification of brain antigen targeted by human IgGs. Overall our data reveal that the alterations of autoantibodies profile both in CSF and serum follow disease staging and progression. However, we demonstrate a fair overlap between CSF and serum suggesting the existence of different immunogenic events. Interestingly, CSF autoantibodies recognized, among others, key players of energy metabolic pathway, including glycolysis and TCA cycle, found oxidatively modified in AD brain studies. These data suggest a potential casual sequence between oxidative damage at brain level, autoantibodies presence in CSF and reduced energy metabolism of AD patients.

Scientific evidence links physical activity to several benefits. Recently, we proposed the idea that exercise can be regarded as a drug. As with many drugs, dosage is of great importance. However, to issue a public recommendation of physical activity in aging is not an easy task. Exercise in the elderly needs to be carefully tailored and individualized with the specific objectives of the person or group in mind. The beneficial effects of exercise in two of the main age-related diseases, sarcopenia and Alzheimer's Disease, are dealt with at the beginning of this report. Subsequently, dosage of exercise and the molecular signaling pathways involved in its adaptations are discussed. Exercise and aging are associated with oxidative stress so the paradox arises, and is discussed, as to whether exercise would be advisable for the aged population from an oxidative stress point of view. Two of the main redox-sensitive signaling pathways altered in old skeletal muscle during exercise, NF-κB and PGC-1α, are also reviewed. The last section of the manuscript is devoted to the age-associated diseases in which exercise is contraindicated. Finally, we address the option of applying exercise mimetics as an alternative for disabled old people. The overall denouement is that exercise is so beneficial that it should be deemed a drug both for young and old populations. If old adults adopted a more active lifestyle, there would be a significant delay in frailty and dependency with clear benefits to individual well-being and to the public's health.

One of the most significant achievements of the twentieth century is the increase in human lifespan. In any period studied, females live longer than males. We showed that mitochondrial oxidative stress is higher in males than females and that the higher levels of estrogens in females protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. The chemical structure of estradiol confers antioxidant properties to the molecule. However, the low concentration of estrogens in females makes it unlikely that they exhibit significant antioxidant capacity in the organism. Therefore we studied the mechanisms enabling estradiol to be antioxidant at physiological levels. Our results show that physiological concentrations of estrogens activate estrogen receptors and the MAPK and NFKB pathway. Activation of NFkB by estrogens subsequently activates the expression of Mn-SOD and GPx. Moreover, we have demonstrated that genistein, the most abundant phytoestrogen in soya, reproduces the antioxidant effect of estradiol at nutritionally relevant concentrations by the same mechanism, both in healthy ageing and in Alzheimer's disease. We conclude that estrogens and phytoestrogens up-regulate expression of antioxidant enzymes via the estrogen receptor and MAPK activation, which in turn activate the NFkB signalling pathway, resulting in the up-regulation of the expression of longevity-related genes.

Skeletal muscle contraction, growth, differentiation and adaptation are governed by complicated biological mechanisms still being studied intensively. Generation of reactive oxygen and nitrogen species (RS) is one of the most prominent events during contractile activity that could influence muscle function and health. While RS generation is known to cause oxidative stress, activate certain pathogenic pathways and aging, they also serve as useful signaling molecules to regulate gene expression of proteins and enzymes that play a vital role in the normal muscle function and defense against detrimental effects of RS. The purpose of the present review is two-fold: first, to provide an overview of cell signaling controlled by a redox sensitive mechanism and its impact on skeletal muscle health and function; and second, to review the various muscular diseases and disorders that have an etiological origin of RS overproduction and/or inadequate antioxidant defense. Given the physiological role of skeletal muscle we will emphasize the importance of physical exercise in promoting cellular antioxidant defense and its benefits in the maintenance of muscle health.