Discussing the Hallmarks of Aging in the Context of Alzheimer's Disease
Researchers here discuss the relevance of the hallmarks of aging to the pathology of Alzheimer's disease. The hallmarks of aging are a mix of causative process and downstream consequences of those causes, and have come to be used as a laundry list of topics in discussions of aging in the years since the original paper was published. The underlying causes of Alzheimer's disease are still much debated, at least in the sense of establishing relative importance and the direction of causation. It is certainly a condition characterized by chronic inflammation and the buildup of protein aggregates, but how do these phenomenon arise? How do they connect to deeper causes of aging? That remains a challenging question to answer; the fastest and best approach is probably to develop the means to repair the damage of aging, repair each in isolation in animal models, and observe the outcome.
Alzheimer's disease (AD) is the most prevalent form of dementia, affecting more than 50 million individuals worldwide. AD is a multifactorial disease with environmental (30%) and genetic (70%) causes. Environmental factors are usually associated with sporadic AD (SAD), while genetic factors are associated with familial AD (FAD) and SAD. Interestingly, FAD and SAD differ in age of onset. According to the age of onset, AD can be divided into two categories of early-onset AD (EOAD) and late-onset AD (LOAD) before or after the age of 65. In all AD cases, approximately 5% are EOAD and 95% are LOAD, indicating that most AD is caused by aging in concert with a complex interaction of genetic and environmental risk factors.
AD, especially LOAD, is associated with aging and is characterized by selective neuronal vulnerability (SNV). However, the relationship between aging and SNV and the molecular basis of AD are not completely understood which need to be urgently elucidated. Aging is the inevitable time-dependent decline in physiological organ integrity, leading to impaired function and increased vulnerability to death. It is characterized by nine tentative hallmarks grouped into three main categories: primary hallmarks (genomic instability, telomere attrition, epigenetic alterations, and loss of proteostasis), antagonistic hallmarks (deregulated nutrient sensing, altered mitochondrial function, and cellular senescence), and integrative hallmarks (stem cell exhaustion and altered intercellular communication).
To date, the role of each aging hallmark in AD development remains unclear. This article will focus on the primary aging hallmarks as these are interconnected with other aging characteristics and are at the base of the hierarchical order of aging features, and have been shown to be related to AD. It is an attempt to improve our understanding of the pathological mechanisms of AD to find potential therapeutic approaches and diagnostic tools.