Stress as a key player in telomere homeostasis maintenance
Although organisms have evolved a set of stress responses to protect
against adverse environmental conditions, protracted stressful
conditions and long-term activation of the stress response negatively
impact health and lifespan (Monaghan 2014). It is now broadly accepted
that chronic stress and lifestyle factors such as oxidative stress,
psychosocial stress, and improper health conditions can affect telomere
dynamics (Epel et al. 2004; Kotrschal et al. 2007; Lin et al. 2012;
Monaghan 2014; Korandová et al. 2018). Reproduction is an energetically
costly activity that increases metabolic rates, ROS production, and
susceptibility to oxidative stress, and it is hypothesized that
oxidative stress may represent a mechanistic link for the inverse
relationship between reproduction and lifespan in both vertebrate and
invertebrate models that acts independently of energy allocation
(Alonso-Alvarez et al. 2004; Wiersma et al. 2004; Krůček et al. 2015;
Sharick et al. 2015; Colominas-Ciuró et al. 2017; Costantini 2018). It
has been demonstrated that resistance to oxidative stress is decreased
during reproduction and that breeding activity increases susceptibility
to oxidative stress (Alonso-Alvarez et al. 2004; Wiersma et al. 2004).
Additionally, resistance to oxidative stress plays a significant role in
shaping fecundity, as a higher fecundity rate was observed in
individuals with higher oxidative protection (Bize et al. 2008). It is
well established that oxidative stress in humans is implicated in
pathological processes in the reproductive tract that contribute to
infertility and poor pregnancy outcomes, and treatments based on
strategies to boost the exhausted antioxidant defense of the
reproductive microenvironment have been suggested (Adeoye et al. 2018).
DNA molecules represent an important target of oxidative damage in
cells, and the most common DNA damage caused by free oxygen radicals is
oxidative modifications of DNA bases such as the formation of
8-oxoguanin. Oxidative DNA lesions are associated with the production of
single-strand breaks that are induced directly or as an intermediate
step in the repair of oxidative base modifications. Due to their high
content of guanine, telomeres are highly sensitive to oxidative damage
and induction of single-strand breaks that interfere with the
replication fork and thus lead to telomere attrition (von Zglinicki
2002; Houben et al. 2007; Coluzzi et al. 2019). In agreement with the
assumption that breeding individuals are more susceptible to oxidative
damage, engaging organisms in reproduction accelerates telomere loss
(Kotrschal et al. 2007; Heidinger et al. 2011).
Bypassing the common negative association between fecundity and
longevity in eusocial reproductives may explain their enhanced oxidative
protection coupled with the fecundity rate. As demonstrated in ants,
young founding queens exhibit immunity and resistance against
environmental and physiological stress, while established older queens
exhibit stimulated oxidative protection (Lucas and Keller 2018; Negroni
et al. 2019). Similarly, data suggesting a role for antioxidant genes in
modulating the lifespan of long-lived reproductives were identified in
Adélie penguins that exhibit an increased antioxidant defense in
response to breeding efforts, while oxidative damage and telomere length
remained unchanged (Beaulieu et al. 2011). When we compared a
few-day-old termite reproductives (with no or very low mating
experience) to greater than 1-year-old reproductives, the old
individuals exhibited highly upregulated oxidative defenses in their
somatic tissues in combination with telomerase activity (Koubová et al.
2021a; our unpublished data).