3.1. Aging and age-related diseases
Throughout the lifespan of an organism, all cell types experience gradual changes that affect their performance either directly or indirectly. This process, known as aging, is a compendium of different cellular and molecular processes, such as DNA-related changes, mitochondrial dysfunction or epigenetic alterations (Lopez-Otin, Blasco, Partridge, Serrano & Kroemer, 2013) that result in morbidity and increased risk of chronic diseases referred to as age-related diseases (ARDs) (Franceschi et al., 2018). Among these, conditions that affect the CNS are frequent, including Alzheimer’s disease (AD) or Parkinson’s disease (PD).
The complex aging phenomenon is one of the most challenging questions for humanity to comprehend. It is important to differentiate between age-associated pathologies and the normal, steady aging process, if such distinction exists. This is a complex paradigm where the boundaries are difficult to stablish. One of the running hypotheses is the continuum hypothesis, which suggests that the aging process and age-related diseases exist on a spectrum, with some individuals experiencing accelerated aging and developing one or more ARDs and others experiencing slower aging and remaining healthy (Franceschi et al., 2018). Studies have found that even seemingly healthy individuals often shows signs of pathology upon post-mortem examination, such as Lewy bodies, β-amyloid (Aβ) plaques or microvascular brain injuries of their brains (Sonnen et al., 2011), leading to increased interest in understanding the molecular hallmarks of aging, prevent and treat ARDs (Franceschi et al., 2018).
However, some experts consider the aging process is just one of the susceptibility factors that contribute to ARD development. Other aspects such as genetic predisposition of age-unrelated genes or exposure to exogenous agents play important roles and the balance of those determine the outcome (Nelson et al., 2011). In this case, a “healthy way of aging” would potentially exist with no collateral ARDs but still different to the phenotype of young individuals. Until this topic is fully explored, this review considers homeostatic aging to be the absence of clinically noticeable pathologies.