Abstract
Alzheimer’s disease (AD) represents the most common form of dementia among older age subjects, and despite decades of studies, the underlying mechanisms remain unresolved. The definition of AD has changed over the past 100 years, and while early-onset AD is commonly related to genetic mutations, late-onset AD is more likely due to a gradual accumulation of age-related modifications. “Normal brain aging” and AD may represent different pathways of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes (ARCs) affecting the brain may be considered as biologic manifestations of increasing entropy, a measure of disorder. Late-onset AD may be regarded as the final effect of a reduced energy production, due to exhausted mitochondria, and an increased entropy in the brain. This unique trajectory enables a bioenergetics-centered strategy targeting disease-stage specific profile of brain metabolism for disease prevention and treatment.
Highlights
Aging is the inevitable biological process that results in a progressive structural and functional decline from the cellular level to whole body function, which leads to reduced ability to adapt to environmental stress and changes
Large population-based studies demonstrate an exponential increase in dementia incidence after 65 years of age, doubling roughly every five years, such that more than 50% of nonagenarians may be expected to suffer from dementia [3]
By exploring brain aging at molecular level, we focus on studies that have examined the role of cellular senescence and age-related changes (ARCs) as biological manifestations of increased entropy
Summary
Aging is the inevitable biological process that results in a progressive structural and functional decline from the cellular level to whole body function, which leads to reduced ability to adapt to environmental stress and changes. Since the 1980s, people aged 85 and over are increasing dramatically, reaching 13% of the population over 65 [6] They are defined as “oldest-old” and represent, today, the fastest growing age group in high-income countries. Normal aging and AD might, represent a different pathway of successful or failed capability to adapt brain structures and cerebral functions. Understanding their similarities and differences could be the key to solve the aging enigma. This is a selective review focused on findings from studies investigating the impact of aging in dementia, and in particular, to try to find differences or similarities between normal aging and AD. The review concludes with a general discussion that focuses on the mechanisms that underlie this unique trajectory, and implications for future research
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