A Long Journey into Aging, Brain Aging, and Alzheimer’s Disease Following the Oxidative Stress Tracks

Abstract

The Editors of the Journal of Alzheimer’s Disease invited Professor Patrizia Mecocci to contribute a review article focused on the importance and implications of her research on aging, brain aging, and senile dementias over the last years. This invitation was based on an assessment that she was one of the journal’s top authors and a strong supporter of the concept that oxidative stress is a major contributor to several alterations observed in age-related conditions (sarcopenia, osteoporosis) and, more significantly, in brain aging suggesting a pivotal role in the pathogenesis and progression of one of the most dramatic age-related diseases, Alzheimer’s disease (AD). Her first pioneering research was on the discovery of high level of 8-hydroxy-2’-deoxyguanosine (OH8dG), a marker of oxidation in nucleic acids, in mitochondrial DNA isolated from cerebral cortex. This molecule increases progressively with aging and more in AD brain, supporting the hypothesis that oxidative stress, a condition of unbalance between the production of reactive oxygen species and antioxidants, gives a strong contribution to the high incidence of AD in old age subjects. OH8dG also increases in peripheral lymphocyte from AD subjects, suggesting that AD is not only a cerebral but also a systemic disease. The role of antioxidants, particularly vitamin E and zinc, were also studied in longevity and in cognitive decline and dementia. This review shows the main findings from Mecocci’s laboratory related to oxidative stress in aging, brain aging, and AD and discusses the importance and implications of some of the major achievements in this field of research.

Gray matter volume and estimated brain age gap are not associated with sleep-disordered breathing in subjects from the ADNI cohort

“…While there is no exact definition for accelerated brain aging, BrainAGE score has been shown to be a sensitive predictor of disease progression in dementia 27–29 . Previous findings on increased BrainAGE score in MCI and AD course 67–69 , are in agreement with the reported accelerated aging of the demented brain shown in-vivo and ex-vivo studies 70 . The BrainAGE score in studies using ADNI ranged from almost zero for patients with stable MCI, to 5.7–6.2 years for patients with progressive MCI, and reached up to 10 years for patients with AD 27 .…”

Oxidative Stress in Cognitive and Epigenetic Aging: A Retrospective Glance

“…Hydrogen peroxide from superoxide produce highly reactive hydroxyl radical that drive the oxidative damage toward the DNA, lipids, and proteins (Halliwell and Gutteridge, 1985). Mitochondria is a major internal source for ROS and hence is also a major target of oxidative damage (Chance et al, 1979); progressive impairment of mitochondria has been implicated in aging and neurodegenerative disorders such as Alzheimer's (Swerdlow and Khan, 2004;Mecocci et al, 2018). The mitochondrial DNA (mtDNA) is vulnerable to the insults of ROS as they lack histones.…”

Oxidative stress in elderly population: A prevention screening study

“…A decline in normal antioxidant defense mechanisms has been observed in the aging brain and in the case of several neurodegenerative diseases. 19 Such a decline increases the vulnerability of the brain to the deleterious effects of oxidative damage; the brains of patients with Alzheimer's disease showed reduced activity of antioxidant enzymes (SOD, catalase, glutathione peroxidase and glutathione reductase) 26,27. Different markers of oxidative stress in the aging brain have been broadly researched, for example 8-OHdG (8-hydroxy-2′-deoxyguanosine) as a biomarker of oxidative DNA damage in the aged brain [28][29][30].…”