The search for physiological markers of health and survival in wild animal populations is attracting a great deal of interest. At present, there is no (and may never be) consensus on such a single, robust marker but of all the proposed physiological markers, telomere length is undoubtedly the most widely studied in the field of evolutionary ecology (Monaghan et al., 2022). 

Broadly speaking, telomeres are non-coding DNA sequences located at the end of chromosomes in eukaryotes, protecting genomic DNA against oxidative stress and various detrimental processes (e.g. DNA end-joining) and thus maintaining genome stability (Blackburn et al., 2015). However, in most somatic cells from the vast majority of the species, telomere sequences are not replicated and telomere length progressively declines with increased age (Remot et al., 2022). This shortening of telomere length upon a critical level is causally linked to cellular senescence and has been invoked as one of the primary causes of the aging process (López-Otín et al., 2023). Studies performed in both captive and wild populations of animals have further demonstrated that short telomeres (or telomere sequences with a fast attrition rate) are to some extent associated with an increased risk of mortality, even if the magnitude of this association largely differs between species and populations (Wilbourn et al., 2018).

The repeated observations of associations between telomere length and mortality risk have called for studies seeking to identify the ecological and biological factors that – beyond chronological age – shape the between-individual variability in telomere length. A wide spectrum of environmental stressors such as the level of exposure to pathogens or the degree of human disturbances has been proposed as possible modulators of telomere dynamics (see Chatelain et al., 2019). However, within species, the relative contribution of various ecological and biological factors on telomere length has been rarely quantified. In that context, the study of Criscuolo and colleagues (2023) constitutes a timely attempt to decipher the relative contribution of environmental and biological factors driving telomere length in nestlings (i.e. when individuals are between 15 and 35 days of age) from a wild population of little owls, Athene noctua.

In addition to chronological age, Criscuolo and colleagues (2023) analysed the effects of two environmental variables (i.e. cohort and habitat quality) as well as three life history traits (i.e. hatching rank, sex and body condition). Among these traits, sex was found to impact nestling’s telomere length with females carrying longer telomeres than males. Traditionally, the among-individuals variability in telomere length during the juvenile period is interpreted as a direct consequence of differences in growth allocation. Fast-growing individuals are typically supposed to undergo more cell divisions and a higher exposure to oxidative stress, which ultimately shortens telomeres (Monaghan & Ozanne, 2018). Whether - despite a slightly female-biased sexual size dimorphism - male little owls display a condensed period of fast growth that could explain their shorter telomere is yet to be determined. Future studies should also explore the consequences of these sex differences in telomere length in terms of mortality risk. In birds, it has been observed that telomere length during early life can predict lifespan (see Heidinger et al., 2012 in zebra finches, Taeniopygia guttata), suggesting that females little owls might live longer than their conspecific males. Yet, adult mortality is generally female-biased in birds (Liker & Székely, 2005) and whether little owls constitute an exception to this rule - possibly mediated by sex-specific telomere dynamics - remains to be explored.   

Quite surprisingly, the present study in little owls did not evidence any clear effect of environmental conditions on nestling’s telomere length, at both temporal and special scales. While a trend for a temporal effect was detected with telomere length being slightly shorter for nestling born the last year of the study (out of 4 years analysed), habitat quality (measured by the proportion of meadow and orchards in the nest environment) had absolutely no impact on nestling telomere length. Recently published studies in wild populations of vertebrates have highlighted the detrimental effects of harsh environmental conditions on telomere length (e.g. Dupoué et al., 2022 in common lizards, Zootoca vivipara), arguing for a key role of telomere dynamics in the emerging field of conservation physiology. While we can recognize the relevance of such an integrative approach, especially in the current context of climate change, the study by Criscuolo and colleagues (2023) reminds us that the relationships between environmental conditions and telomere dynamics are far from straightforward. Depending on the species and its life history, telomere length in early life could indeed capture very different environmental signals.

References

Blackburn, E. H., Epel, E. S., & Lin, J. (2015). Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection. Science, 350(6265), 1193-1198. https://doi.org/10.1126/science.aab3389
 
Chatelain, M., Drobniak, S. M., & Szulkin, M. (2019). The association between stressors and telomeres in non-human vertebrates: A meta-analysis. Ecology Letters, 23, 381-398. https://doi.org/10.1111/ele.13426
 
Criscuolo, F., Fache, I., Scaar, B., Zahn, S. & Bleu, J. (2023). Telomere length vary with sex, hatching rank and year of birth in little owls, Athene noctua. EcoEvoRxiv, ver.4, peer-reviewed and recommended by PCI Evol Biol. https://doi.org/10.32942/X2BS3S
 
Dupoué, A., Blaimont, P., Angelier, F., Ribout, C., Rozen-Rechels, D., Richard, M., & Le Galliard, J. F. (2022). Lizards from warm and declining populations are born with extremely short telomeres. Proceedings of the National Academy of Sciences, 119(33), 2201371119. https://doi.org/10.1073/pnas.2201371119
 
Heidinger, B. J., Blount, J. D., Boner, W., Griffiths, K., Metcalfe, N. B., & Monaghan, P. (2012). Telomere length in early life predicts lifespan. Proceedings of the National Academy of Sciences, 109(5), 1743-1748. https://doi.org/10.1073/pnas.1113306109
 
Liker, A., & Székely, T. (2005). Mortality costs of sexual selection and parental care in natural populations of birds. Evolution, 59(4), 890-897. https://doi.org/10.1111/j.0014-3820.2005.tb01762.x
 
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023). Hallmarks of aging: An expanding universe. Cell, 186(2), 243-278. https://doi.org/10.1016/j.cell.2022.11.001
 
Monaghan, P., Olsson, M., Richardson, D. S., Verhulst, S., & Rogers, S. M. (2022). Integrating telomere biology into the ecology and evolution of natural populations: Progress and prospects. Molecular Ecology, 31(23), 5909-5916. https://doi.org/10.1111/mec.16768
 
Monaghan, P., & Ozanne, S. E. (2018). Somatic growth and telomere dynamics in vertebrates: Relationships, mechanisms and consequences. Phil. Trans. R. Soc. B, 373(1741), 20160446. https://doi.org/10.1098/rstb.2016.0446
 
Remot, F., Ronget, V., Froy, H., Rey, B., Gaillard, J., Nussey, D. H., & Lemaitre, J. (2022). Decline in telomere length with increasing age across nonhuman vertebrates: A meta‐analysis. Molecular Ecology, 31(23), 5917-5932. https://doi.org/10.1111/mec.16145
 
Wilbourn, R. V., Moatt, J. P., Froy, H., Walling, C. A., Nussey, D. H., & Boonekamp, J. J. (2018). The relationship between telomere length and mortality risk in non-model vertebrate systems: A meta-analysis. Phil. Trans. R. Soc. B, 373(1741), 20160447. https://doi.org/10.1098/rstb.2016.0447

In most animal species, males and females display distinct survival prospect, a phenomenon known as sex gap in longevity (SGL, Marais et al. 2018). The study of SGLs is crucial not only for having a full picture of the causes underlying organisms’ health, aging and death but also to initiate the development of sex-specific anti-aging interventions in humans (Austad and Bartke 2015). Three non-mutually evolutionary causes have been proposed to underlie SGLs (Marais et al. 2018). First, SGLs could be the consequences of sex-differences in life history strategies. For example, evolving dimorphic traits (e.g. body size, ornaments or armaments) may imply unequal physiological costs (e.g. developmental, maintenance) between the sexes and this may result in differences in longevity and aging. Second, mitochondria are usually transmitted by the mother and thus selection is blind to mitochondrial deleterious mutations affecting only males. Such mutations can freely accumulate in the mitochondrial genome and may reduce male longevity, a phenomenon called the mother’s curse (Frank and Hurst 1996). Third, in species with sex chromosomes, all recessive deleterious mutations will be expressed on the single X chromosome in XY males and may reduce their longevity (the unguarded X effect). In addition, the numerous transposable elements (TEs) on the Y chromosome may affect aging. TE activity is normally repressed by epigenetic regulation (DNA methylation, histone modifications and small RNAs). However, it is known that this regulation is disrupted with increasing age. Because of the TE-rich Y chromosome, more TEs may become active in old males than in old females, generating more somatic mutations, accelerating aging and reducing longevity in males (the toxic Y effect, Marais et al. 2018).
The relative contributions of these different effects to SGLs remain unknown. Sex-differences in life history strategies have been considered as the most important cause of SGLs for long (Tidière et al. 2015) but this effect remain equivocal (Lemaître et al. 2020) and cannot explain alone the diversity of patterns observed across species (Marais et al. 2018). Similarly, while studies in Drosophila and humans have shown that the mother’s curse contributes to SGLs in those organisms (e.g. Milot et al. 2007), its contribution may not be strong. Recently, two large-scale comparative analyses have shown that in species with XY chromosomes males show a shorter lifespan compared to females, while in species with ZW chromosomes (a system in which the female are the heterogametic sex and are ZW, and the males ZZ) the opposite pattern is observed (Pipoly et al. 2015; Xirocostas et al. 2020). Apart from these correlational studies, very little experimental tests of the effect of sex chromosomes on longevity have been conducted. In Drosophila, the evidence suggests that the unguarded X effect does not contribute to SGLs (Brengdahl et al. 2018). Whether a toxic Y effect exists in this species was unknown.
In a very elegant study, Brown et al. (2020) provided strong evidence for such a toxic Y effect in Drosophila melanogaster. First, they checked that in the D. melanogaster strain that they were studying (Canton-S), males were indeed dying younger than females. They also confirmed that in this strain, as in others, the male genomes include more repeats and heterochromatin than the female ones using cytometry. A careful analysis of the heterochromatin (using H3K9me2, a repressive histone modification typical of heterochromatin, as a proxy) in old flies revealed that heterochromatin loss was much more important in males than in females, in particular on the Y chromosome (but also to a lesser extent at the pericentromric regions of the autosomes). This change in heterochromatin had two outputs, they found. First, the expression of the genes in those regions was affected. They highlighted that many of such genes are involved in immunity and regulation with a potential impact on longevity. Second, they found a striking TE reactivation. These two effects were stronger in males. While females showed clear reactivation of 6 TEs, with the total fraction of repeats in the transcriptome going from 2% (young females) to 4.6% (old females), males experienced the reactivation of 32 TEs, with the total fraction of repeats in the transcriptome going from 1.6% (young males) to 5.8% (old males). It appeared that most of these TEs are Y-linked. And when focusing on Y-linked repeats, they found that 32 Y-linked TEs became upregulated during male aging and the fraction of Y-linked TEs in the transcriptome increased ninefold.
All these observations clearly suggested that male longevity was decreased because of a toxic Y effect. To really uncover a causal relationship between having a Y chromosome and shorter longevity, Brown et al. (2020) artificially produced flies with atypical karyotypes: X0 males, XXY females and XYY males. This is very interesting as they could uncouple the effect of the phenotypical sex (being male or female) and having a Y chromosome or not, as in fruit flies sex is determined not by the Y chromosome but by the X/autosome ratio. Their results are striking. They found that longevity of the X0 males was the highest (higher than XX females in fact), and that of the XYY males the lowest. Females XXY had intermediate longevities. Importantly, this was found to be robust to genomic background as results were the same using crosses from different strains. When analysing TEs of these flies, they found a particularly strong expression of the Y-linked TEs in old XXY and XYY flies. Interestingly, in young XXY and XYY flies Y-linked TEs expression was also strong, suggesting the chromatin regulation of the Y chromosome is disrupted in these flies.
This work points to the idea that SGLs in D. melanogaster are mainly explained by the toxic Y effect. The molecular details however remain to be elucidated. The effect of the Y chromosome on aging might be more complex than envisioned in the toxic Y model presented above. Brown et al. (2020) indeed found that heterochromatin loss was globally faster in males, both at the Y chromosome and the autosomes. The organisation of the nucleus, in particular of the nucleolus, which is involved in heterochromatin maintenance, involves the sex chromosomes in D. melanogaster as discussed in the paper, and may explain this observation. The epigenetic status of the Y chromosome is known to affect that of all the autosomes in Drosophila (Lemos et al. 2008). Also, in Brown et al. (2020) most of the work (in particular the genomic part) has been done on Canton-S. Only D. melanogaster was studied but limited data suggest different Drosophila species may have different SGLs. The TE analysis is known to be tricky, different tools to analyse TE expression exist (e.g. Lerat et al. 2017; Lanciano and Cristofari 2020). Future work should focus on testing the toxic Y effect on other D. melanogaster strains and other Drosophila species, using different tools to study TE expression, and on dissecting the molecular details of the toxic Y effect.

References

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Brown, E. J., Nguyen, A. H., and Bachtrog, D. (2020). The Y chromosome may contribute to sex-specific ageing in Drosophila. Nature ecology and evolution, 4(6), 853–862. 10.1038/s41559-020-1179-5 or preprint link on bioRxiv
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Marais, G., Gaillard, J. M., Vieira, C., Plotton, I., Sanlaville, D., Gueyffier, F., and Lemaitre, J. F. (2018). Sex gap in aging and longevity: can sex chromosomes play a role?. Biology of sex differences, 9(1), 33. 10.1186/s13293-018-0181-y
Milot, E., Moreau, C., Gagnon, A., Cohen, A. A., Brais, B., and Labuda, D. (2017). Mother's curse neutralizes natural selection against a human genetic disease over three centuries. Nature ecology and evolution, 1(9), 1400–1406. 10.1038/s41559-017-0276-6
Pipoly, I., Bókony, V., Kirkpatrick, M., Donald, P. F., Székely, T., and Liker, A. (2015). The genetic sex-determination system predicts adult sex ratios in tetrapods. Nature, 527(7576), 91–94. 10.1038/nature15380
Tidière, M., Gaillard, J. M., Müller, D. W., Lackey, L. B., Gimenez, O., Clauss, M., and Lemaître, J. F. (2015). Does sexual selection shape sex differences in longevity and senescence patterns across vertebrates? A review and new insights from captive ruminants. Evolution; international journal of organic evolution, 69(12), 3123–3140. 10.1111/evo.12801
Xirocostas, Z. A., Everingham, S. E., and Moles, A. T. (2020). The sex with the reduced sex chromosome dies earlier: a comparison across the tree of life. Biology letters, 16(3), 20190867. 10.1098/rsbl.2019.0867