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.