2 Although these data are open to discussion and also clearly refer to a very

old age, which in fact is at the upper limit of human longevity, they nevertheless reveal the intimate relationship between age and disease. Life expectancy is continuing to increase, thus making longevity “one of humanity’s most astonishing successes.”3 Thus, it is important to decipher not only the mechanisms underlying this prolonged human longevity, but also the complex factors that make humans more vulnerable to pathology and neurodegenerative Inhibitors,research,lifescience,medical BIBR-1532 diseases. It is also important to understand the factors that delay pathological aging, because by so doing we can emphasize a lifestyle that promotes healthy aging of the entire body, including the brain. Current research provides an increasing body of evidence supporting the existence of an environmentdependent plasticity of the brain and the relevance of this plasticity for aging and neurodegenerative diseases.1,4-6 The aim of this article is to first review the anatomical and functional changes Inhibitors,research,lifescience,medical of the aging brain, and second to review the reported plastic effects of environmental enrichment on different neurobiologicai parameters. This article will also review the effects of caloric restriction, physical exercise, and stress, with special emphasis on Inhibitors,research,lifescience,medical glucocorticoids on the aging brain. It will be proposed that lifestyle factors are powerful

instruments that promote a delay in the appearance of age-related deficits and lead to a Inhibitors,research,lifescience,medical healthy and successful aging of the brain. Genome, ambiome, and longevity Aging is an endogenous, progressive, and deleterious process that does not seem to be genetically programmed, but rather results from many molecular events that cause an accumulation of damaged cellular components including proteins,

DNA, and cell membranes.7,8 This Inhibitors,research,lifescience,medical deleterious process is mostly due to an increase in oxidative stress free radicals and mitochondrial instability, which results in a lower production of ATP, which would render less energy available to invest in the maintenance and repair of the organism.9 Longevity, which refers to how long the process of aging will continue, is in part governed by genes that promote molecular mechanisms controlling antioxidant activity and the maintenance and repair of damage induced by free radicals.7 Nonetheless, today we are starting to understand Phosphatidylinositol diacylglycerol-lyase that the increase in longevity that we are currently witnessing does not seem to rely as much on those genes already mentioned, but rather on genes that become activated during aging by different lifestyle features and the proteins encoded by these activated genes.9,10,11 Lifestyle factors seem to be of crucial importance, not because they can determine how long we will live, but rather because they can determine how healthily we will age and thus maintain an independent life during aging.