A role of telomerase to eliminate the cost of reproduction
depending on the type of reproduction strategy
The telomere-related function of telomerase requires passage into S
phase, and appears to be coupled to cell proliferation (Blasco 2007).
Regrettably, most of the non-model organism studies mentioned above did
not provide detailed information relating telomerase activity to DNA
replication or tissue proliferation status, and the presence of
telomerase in post-mitotic tissues, if observed, was explained by a
non-canonical, and yet unknown, function of telomerase (reviewed in
Gomes et al. 2010). In this regard, it is useful to mention that a wide
range of TERT alternatively spliced variants were discovered in a
variety of animal species, and TERT alternative splicing is thought to
be linked to non-canonical telomerase functions such as those in cell
proliferation, cancer development, or regeneration process (Yi et al.
2001; Hrdličková et al. 2012; Listerman et al. 2013; Lai et al. 2017;
Slusher et al. 2020; Penev et al. 2022). The investigation of the
evolutionary history of TERT across different metazoan taxa revealed
that the selection of exons for alternative splicing appears to be
highly variable between taxa, indicating diverse functions of TERT
involved in animal life histories (Lai et al. 2017). Based on this and
the data I am presenting below it is tempting to ask whether telomerase
may act as one of reproductive fitness traits.
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). Resistance to oxidative stress plays a significant
role in shaping fecundity; for instance, higher fecundity rates were
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).
Furthermore, in passerine birds, it has been demonstrated that
resistance to oxidative stress is decreased during their reproduction
and that breeding activity increases susceptibility to oxidative stress
(Alonso-Alvarez et al. 2004; Wiersma et al. 2004). 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; Bauch et al. 2013).
On the other hand, there are numerous studies showing that increased
breeding constraints or reproductive status appear to prioritize
self-maintenance as documented by the increased lifespan expectancy,
telomere length, telomerase activity, or antioxidant defense. It has
been demonstrated that (1) workers in many eusocial insect species
restore their ability to reproduce if the queen in the colony has been
lost, and the transition of the workers into reproductive state is
associated with their substantial lifespan extension (Hartmann and
Heinze 2003; Dixon et al. 2014; Kohlmeier et al. 2017; Kuszewska et al.
2017; Majoe et al. 2021) and improved resilience to oxidative stress
(Schneider et al. 2011; Lucas and Keller 2018; Negroni et al. 2019;
Majoe et al. 2021). (2) It has been shown that in contrast to the
decline of antioxidant protection during mating in the short-lived
passerine birds (Alonso-Alvarez et al. 2004; Wiersma et al. 2004;
Kotrschal et al. 2007; Heidinger et al. 2011; Bauch et al. 2013), the
long-lived Adélie penguins exhibited an increased antioxidant defense
and unchanged telomere length in response to breeding efforts (Beaulieu
et al. 2011). (3) The positive correlation between telomere length (and
presumably telomerase activity), age and reproduction effort were
observed in the edible dormice (Glis glis ), a hibernating
long-lived rodent with a lifespan reaching 13 years. Although telomere
length in this species is shortened over the hibernation season during
periods of rewarming, which is associated with increased oxidative
stress, it is elongated during the summer active season, when the
animals mate. Longitudinal telomere length measurements revealed that
the telomere-length re-elongation resulted in a gradual telomere
lengthening with age of the individuals together with the likelihood of
their reproduction (Hoelzl et al. 2016). (4) A lifelong somatic activity
of telomerase accompanied by steady or even increasing reproduction rate
with advancing age is observed in numerous reptile or fish species with
indeterminate growth (Gomes et al. 2010; Schwartz and Bronikowski 2011).
For instance, bigmouth buffalo (Ictiobus cyprinellus ), which
displays some of the longest lifespans among vertebrates (>
100 years), has indeterminate growth and fecundity that increases with
size and thus with age of individuals. In contrast to the common
expectation, no telomere length decline was observed in old individuals
of this species, along with declines in other physiological systems such
as stress response and immune function; instead, all the tested
parameters improved their efficiencies with age (Sauer et al. 2021). (5)
It is well-known that the fertility rate of termite queens increases
with age along with their body mass, which, based on the evidence shown
above, appears to be consistent with their increasing somatic telomerase
activity (Adams and Atkinson 2008; Adams et al. 2008; Nozaki and
Matsuura 2019; Koubová et al. 2021a).
It is widely known that body mass in terrestrial mammals is negatively
correlated with the fecundity rate of the species (Allainé et al. 1987;
Werner and Griebeler 2011), which is reflected by the litter size,
interlitter intervals, or gestation length. Based on this assumption, we
can ask whether the necessity to maintain telomerase activity in somatic
cells of small but highly fecund mammal species observed by Gomes et al.
(2010) reflects a different reproduction strategy of the species and
their specific demands during reproduction rather than their body size.
The somatic telomerase activity or longer telomeres (>
25kb) do tend to be correlated with shorter gestation periods, as
observed in Eulipotyphia, Chiroptera, and even two Carnivora species
(steppe polecat and tiger); in Rodentia, Lagomorpha, Afrosoricida, and
Macroscelidea they are associated with short gestation periods along
with multiple litters per year, and in some cases also with the
increased litter size (Figure 1). Despite the lack of telomerase
activity, Diprotodontia have short gestation periods (Figure 1), which,
however, might reflect that youngs in the species are born at a
precocious stage of development.
Based on this observation, it is tempting to speculate that somatic
telomerase activity in eusocial insect reproductives, as well as in the
small mammals or potentially other animal or plant species, may serve a
non-canonical function of protecting individuals against reactive oxygen
species produced due to exacerbated metabolic stress during
reproduction, and may simply reflect a more widespread phenomenon.
Although validity of this hypothesis needs to be tested, we can infer
from all the data that telomerase expression patterns differ greatly
across species, life stages, and conditions, implying that telomerase is
involved in the organism’s adaptive potential and individual fitness,
and that telomerase expression might co-evolved as a pleiotropic
regulator involved in the life-history trade-offs between growth,
maintenance, and reproduction. More precise information connecting
telomerase activity to distinct reproductive strategies and lifespan
expectancies, along with different cellular, physiological, and
ecological features in various species across the animal and plant
kingdoms, would help us better understand the role of telomerase in this
aspect. We can assume that resolving the connections between these
trade-offs would lead to new and intriguing directions for ecology and
evolutionary biology study.
Conflicts of Interest Statement Author declares no conflict of
interest.
Acknowledgements I thank James Mason and anonymous reviewers
for their careful reading of my manuscript and their many insightful
comments and suggestions. This study was supported by Strategy AV21,
Diversity of Life and Health of Ecosystems.