The aging explanation theories
Aging is characterized by a series of cellular and tissue damage events
that accumulate with age and result in impaired functioning of the
organism that eventually leads to death. Although countless theories
have been proposed as universal explanations for the aging process, none
of these theories are entirely satisfactory. Instead, to explain the
aging process these theories are applied in a complex way to provide a
combinatorial explanation (Jin 2010).
Aging theories exist in two primary categories that include
programmed and damage theories. The most established theory of aging is
the mitochondrial free radical theory of aging, proposing that aging is
a result of accumulating cellular damage caused by free radicals, and
mitochondria act as the primary source of reactive oxygen species (ROS)
(Harman 1956; Harman 1972). Generation of mitochondrial ROS such as
hydroxyl radicals, hydrogen peroxide, and superoxide radicals primarily
occurs during electron transport during oxidative phosphorylation.
According to this theory, mitochondrial DNA (mtDNA) due to its proximity
to ROS generation is considered the prime ROS target, and this targeting
of mtDNA leads to the accumulation of ROS-induced damage in mitochondria
and loss of functionality with age (Murphy 2009).
The programmed theory of aging proposes that aging is the result of a
program that acts through gene expression where certain genes are
switched on or off such as genes of the immune system or telomerase
activity, both of which decline over time (Davidovic et al. 2010; Jin
2010; Fathi et al. 2019). Alternatively, aging is explained as a
continuation of the program for developmental growth (acting as a
quasi-program) that exerts a deleterious effect on adult individuals.
Together with the antagonistic pleiotropy hypothesis, this theory is
based on the assumption that evolution favors genes that increase
fitness in early life despite the knowledge that they are harmful in
later life (Blagosklonny 2010).
Regardless of any theory, aging is linked to multiple cellular processes
that are interconnected and act in numerous cell organelles (Zheng et
al. 2019). It has been demonstrated that the aging process is associated
with changes in epigenomic information (Chittka and Chittka 2010; Lyko
et al. 2010; Ben-Avraham et al. 2012; Herb et al. 2012; He et al. 2017)
that affect the expression levels of aging-related genes (Kaiwen et al.
2018) and lead to alterations in numerous aging-related factors such as
antioxidant protection (Kurz et al. 2004; Corona et al. 2005),
nutrient-sensing pathways, energy homeostasis, and mitochondrial
functioning (Ozawa 1997; Aamodt 2009; Blagosklonny 2010; Cui et al.
2012; Antikainen et al. 2017).