LIFE HISTORY

Senescence in immunity againsthelminth parasites predicts adultmortality in a wild mammalH. Froy1,2*, A. M. Sparks1,3, K. Watt1, R. Sinclair1, F. Bach4, J. G. Pilkington1,J. M. Pemberton1, T. N. McNeilly5, D. H. Nussey1

Our understanding of the deterioration in immune function in old age—immunosenescence—derives principally from studies of modern human populations and laboratory animals.The generality and significance of this process for systems experiencing complex, naturalinfections and environmental challenges are unknown. Here, we show that late-life declinesin an important immune marker of resistance to helminth parasites in wild Soay sheeppredict overwinter mortality. We found senescence in circulating antibody levels against ahighly prevalent nematode worm, which was associated with reduced adult survivalprobability, independent of changes in body weight. These findings establish a role forimmunosenescence in the ecology and evolution of natural populations.

Demographic senescence, the decline insurvival prospects and fertility with age, iswell documented in wild vertebrates andis known to play an important role in thedynamics of natural populations (1–3). Bio-

gerontologists have made great strides towardunderstanding the genetic and physiological pro-cesses underpinning senescence in laboratory or-ganisms (4–6), but we do not yet know whethersimilar mechanisms drive demographic aging un-der natural conditions (1, 3). Declining immunefunction in old age, or immunosenescence, iswidely observed and associated with age-relatedincreases in morbidity and mortality in laboratoryrodents and humans (7–9). Parasites represent amajor selective force in natural populations, andthe ability to mount effective immune defensesagainst them represents a critical determinantof fitness in wild animals (10, 11). A growing body

of evidence suggests that immunosenescencealso occurs in natural populations: several recent,largely cross-sectional vertebrate field studies havedocumented age-related variation in immunemark-ers across adulthood (12). However, the absenceof large-scale longitudinal studies simultaneouslymeasuring parasites, immunity, health, and demog-raphy in the wild has limited our ability to testhow declines in immune function affect ecologicaland evolutionary processes (12). There is a similarscarcity of human studies linking within-individualchanges in immune phenotype in old age withclinical outcomes (9).Gastrointestinal nematode parasites are im-

portant drivers of selection in wild vertebratesystems (13, 14). Despite the global impact ofhelminth parasites (15, 16), the potential for senes-cent declines in immune-mediated resistanceto helminth infection and the consequences for

human, livestock, and wildlife health have rarelybeen considered. Studies of lab mice, humans,and domestic ruminants show that resistance tosuch worm infections is dependent on T helpertype 2 (TH2) immune responses (17), with a keycontribution from serum antibodies (18, 19). Thereis evidence from wild mammals and humans thatthe intensity of worm burdens may increasein later adulthood (20, 21), and cross-sectionalstudies in laboratory mice suggest TH2 functionand anti-worm antibody production may be com-promised in old age (22–24). In particular, twostudies found that elderly mice had a reducedor delayed immunoglobulin G (IgG) antibodyresponse to worm infection (22, 24), suggestingthat this could be an important marker of im-munosenescence. Deterioration in TH2-mediatedimmunity to worms may therefore be responsi-ble for increasing burdens and negative healthoutcomes in later life, but currently longitudinalstudies testing for associations among immunity,worm burden, and components of fitness arecompletely lacking.We used an unmanaged population of Soay

sheep on the remote St. Kilda archipelago inScotland, which has been the subject of detailedstudy since 1985 (25), to test for fitness conse-quences of senescent declines in immunity ina wild population. First-winter lamb mortalityis often high in this population (25). Amongstindividuals that survive to adulthood, mean lon-gevity is 5.5 years for females (maximum 16 years)and 2.7 years for males (maximum 10 years).Demographic senescence is well-documented inthis population, with female fecundity and sur-vival of both sexes declining progressively starting

RESEARCH

Froy et al., Science 365, 1296–1298 (2019) 20 September 2019 1 of 3

1Institute of Evolutionary Biology, University of Edinburgh,Edinburgh, UK. 2Centre for Biodiversity Dynamics, NorwegianUniversity of Science and Technology, Trondheim, Norway.3School of Biology, Faculty of Biological Sciences, University ofLeeds, Leeds, UK. 4Institute of Immunology and Infection Research,University of Edinburgh, Edinburgh, UK. 5Moredun ResearchInstitute, Pentlands Science Park, Bush Loan, Penicuik, UK.*Corresponding author. Email: hannah.froy@ntnu.no

Fig. 1. Senescent declines in circulating anti–T. circumcincta IgG pre-dict overwinter mortality in Soay sheep. (A) Levels of IgG-Tc declined asSoay sheep approached death. Points and error bars show raw datamedians and standard errors (black circles indicate females, gray trianglesindicate males), and lines show predictions from a linear mixed-effectsmodel (Table 2) with 95% confidence intervals (gray shading). (B) Annualoverwinter survival probability was not related to an individual’s mean levels

of IgG-Tc measured over adulthood, as indicated by the regression slopefor the among-individual effect of IgG-Tc on survival estimated from abivariate model (table S4). (C) Individuals with relatively low levels of IgG-Tccompared with their average were less likely to survive the winter, asindicated by the within-individual effect of IgG-Tc on survival (also estimatedfrom the bivariate model; table S4). Points show raw data, and black linesshow regression slopes with 95% credible intervals shaded in gray.

Corrected 13 December 2019. See full text. on A

pril 1, 2021

http://science.sciencemag.org/

Dow

nloaded from

https://science.sciencemag.org/content/365/6459/1296http://science.sciencemag.org/

at ~5 years (26). The sheep are host to a diversecommunity of gastrointestinal nematode parasites,including several highly prevalent strongyle spe-cies, which have been linked to gut pathologyand overwinter mortality (27). Counts of nema-tode eggs from fecal samples provide an impor-tant proxy of parasite burden (27). Fecal egg counts(FEC) increase with advanced age in adult Soaysheep, which could reflect a loss of immune-mediated host control of parasite infection inlater life (26).Our previous work has established levels of

plasma IgG binding antigen from Teladorsagiacircumcincta (IgG-Tc), a highly prevalent wormin both wild Soay and domestic sheep, as animportant marker of immunity to helminths inthis system. In adult Soay sheep, plasma levelsof IgG-Tc in summer are weakly correlated withother immune measures, including other anti-body isotypes (IgA, IgM, and IgE) binding thesame Tc antigens (28–30). IgG-Tc levels are alsonegatively associated with FEC and positively as-sociated with subsequent winter survival, inde-pendently of other humoral and cellular immunemeasures (28–30). Further analysis showed thatIgG-Tc correlates strongly (correlation coefficientr > 0.9) with levels of IgG binding antigen from arange of strongyle species (materials andmethods;fig. S1), only someofwhich are present on St. Kilda,suggesting a high degree of cross-reactivity. Wealso showed that, regardless of which strongylespecies is used, levels of binding by this IgG pre-dict subsequent survival (table S1). This impli-cates IgG-Tc as a potentially powerful markerof specific immunity to helminths in this studysystem and motivated an in-depth study of thecauses of its association with adult mortality.Using measurements of IgG-Tc by enzyme-linkedimmunosorbent assay (ELISA) from 2215 longi-tudinal blood samples collected from 797 adultsheep aged 3 years or older over 26 years (1990–2015) on St. Kilda (materials and methods; tableS2), we tested whether IgG-Tc showed within-individual declines in later life consistent withimmunosenescence, and whether such declineswere associatedwith parasite burden, bodyweight,and subsequent mortality.We found senescence in our marker of resist-

ance to nematode infection in wild Soay sheep.Levels of IgG-Tc declined with age [regressionslope b = −0.006, 95% confidence interval (CI) =−0.010 to −0.002; table S3A], but because in-dividuals may senesce at different rates, the num-ber of years an individual is away from deathmaybe a better reflection of their biological agingpatterns than chronological age itself (31). Ac-cordingly, we found that years before deathexplained more variation in IgG-Tc than chron-ological age (Table 1). Levels of IgG-Tc declinedas adults approached death, and the relation-ship was best described by a threshold functionwith the decline accelerating over the final yearof life (Fig. 1A and table S3B). Males had loweraverage levels of IgG-Tc than females (Table 2),but there was no detectable interaction betweenyears before death and sex, indicating that thepattern of within-individual changes in IgG-Tc

was consistent between the sexes. IgG-Tc levelswere highly repeatable across the adult life-times of sheep, with 58% of the variance in ourdataset explained by individual identity (repeat-ability = 0.576, 95% CI = 0.542 to 0.609). Theseresults show that despite consistent among-individual differences in IgG-Tc across theirlifetimes, average antibody levels declinedwithinindividuals as they approached death.Senescent declines in immunity were associ-

ated with increased subsequent mortality risk.We used a bivariate mixed-effects model to esti-mate the covariance between IgG-Tc measured insummer and the probability of survival over thesubsequentwinter at three different levels: among-individual, among-year, and within-individual(see materials and methods; 2202 observations of796 individuals over 26 years). Among-individualcovariance captures the association between an

individual’s average adult antibody level and theiroverall life span, whereas within-individual (orresidual) covariance represents the association be-tween the deviation in IgG-Tc from an individual’smean value and that individual’s prospects of sur-viving the following winter. Among-year covariancereflects associations between the population’saverage antibody levels andmortality rates acrossyears. We found that covariance between IgG-Tcand survival was statistically significant only atthewithin-individual level, andnot at either among-individual or among-year levels (Fig. 1 and tableS4). The absence of any among-individualcovariance reveals that consistent differences inimmunity across adulthood, potentially associ-atedwith genotype or early-life environment, didnot predict life span (Fig. 1B). However, the posi-tive within-individual covariance indicates thatindividuals showing a within-individual decline

Froy et al., Science 365, 1296–1298 (2019) 20 September 2019 2 of 3

Table 1. Comparing the explanatory power of linear models with different fixed-effects structuresfor levels of IgG-Tc in Soay sheep. Anti–T. circumcincta IgG was measured in plasma samplescollected from adult sheep in summer 1990–2015 (n = 1869 observations of 651 individuals) All models

included individual, year, and ELISA plate as random intercept terms. Sex was included as a two-level

factor, age as a linear covariate, and years before death (YBD) as a threshold function with a break point at1 year (see table S3).The number of parameters is indicated by degrees of freedom (df), and DAIC is the

difference in the Akaike information criterion value compared with the best model (highlighted in bold).

Fixed-effects structure df AIC DAIC

Null 5 −1662.46 44.63. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Sex 6 −1671.53 35.56. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Age 6 −1670.06 37.02. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold 7 −1703.29 3.80. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Age + sex 7 −1680.56 26.53. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold + sex 8 −1707.09 0.00. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold + age 8 −1702.79 4.30. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Age × sex 8 −1678.72 28.37. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold × sex 10 −1703.68 3.40. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold + age + sex 9 −1705.38 1.71. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold + age × sex 10 −1704.31 2.78. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold × sex + age 11 −1702.01 5.08. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

YBD threshold × sex + age × sex 12 −1700.42 6.67. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Table 2. Fixed and random effect estimates from the best model of IgG-Tc in Soay sheep. Showingthe effect of years before death (YBD) and sex (relative to females) on levels of circulating IgG-Tc in

adult sheep. Estimates are given with 95% confidence intervals from 1000 bootstrap replicates.

Estimate Lower 95% CI Upper 95% CI P value

Random effects. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Individual 0.023 0.020 0.026 —. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... .. ... ... .. ... ... .. ... ... .. ... .. ... ... .

Year 0.001

in IgG-Tc had a reduced survival probability thefollowing winter (Fig. 1C). These data show thatlongitudinal changes in a marker of immune re-sistance in later adulthood predict mortality riskin the wild and indicate that immunosenescencemay play an important role in age-related declinesin demographic rates in natural populations.Thewithin-individual association between IgG-

Tc and survival remained when associationswith FEC, our index of parasite burden, and bodyweight were accounted for (Fig. 2 and table S5).We ran a multivariate mixed-effects model thatincluded all four measures as response variables,and again estimated covariance among the termsat the among-individual, among-year, and within-individual levels (see materials and methods).As expected for a marker of resistance to worminfection, FEC and IgG-Tc were negatively asso-ciated at the within-individual level (table S5).Higher levels of IgG-Tc at both among- andwithin-individual levels were associated withincreased body weight, and weight covariedpositively with survival at all three levels [tableS5; accounting for variation in structural size(hindleg length) in models of body weight didnot change our results, table S6]. We used thismultivariate approach to test for independenteffects of immunity, parasite burden, and weighton subsequent survival, while accounting for theinterdependencies among these terms (analo-gous to a multiple regression; see materialsand methods). We found that within-individ-ual deviation in IgG-Tc was still a predictor ofoverwinter survival (Fig. 2). The independence ofthe immunity–survival relationship from bodyweight suggests that it was not mediated byvariance in individual body condition or re-source availability, and that late-life declinesin body weight and immunity reflect separatephysiological senescence pathways. This high-lights the complex, multifaceted nature of phys-iological senescence in wild animals and the needfor large-scale multivariate studies to understandwhich processes are most important for late-lifefitness across taxa and ecological contexts (32).

Few studies to date have investigated how theimmune system changes in later adulthood inresponse to pathogenic, chronically infective hel-minth parasites. Our analyses show that associa-tions among adult infection, immunity, and survivalare not driven by constitutive among-individualdifferences, determined by genetics or early-lifeconditions, but rather by within-individual var-iation late in life linked to senescence. Studies inlaboratorymice suggest the TH2 response to worminfection becomes compromised in old age, andthat the host’s ability to resist infection declines asa result (22–24). Although the observed within-individual negative correlation between FEC andIgG-Tc is consistent with a resistance functionfor this immunemarker, ourmultivariatemodelsshow that longitudinal declines in IgG-Tc predictmortality independently of FEC, suggesting thisrelationship with mortality is not solely mediatedby reduced worm burden. This may reflect theindirect and therefore inherently noisy relation-ship between FEC and actual wormburden. How-ever, changes in host tolerance of worm infection,a processwe have previously linked to variation inhost fitness in our study system (33) or density-independent alterations in parasite behavior inresponse to host physiological deterioration [e.g.,helminth suppression of the immune response(17)] could also explain the relationship betweenIgG-Tc and survival. Our results suggest thatchanges in the interactions between host immu-nity and helminth infection during adulthoodcould have implications for host ecological dy-namics, helminth epidemiology, andhost-parasiteco-evolution in wild vertebrates. The focus on thedevelopment of immunity to helminths in earlylife in humans and livestock is understandable,but our data suggest that changes in host im-mune responses to worm infection occur inmammals during later life.

REFERENCES AND NOTES

1. D. H. Nussey, H. Froy, J.-F. Lemaitre, J.-M. Gaillard,S. N. Austad, Ageing Res. Rev. 12, 214–225 (2013).

2. D. A. Roach, J. R. Carey, Annu. Rev. Ecol. Evol. Syst. 45,421–443 (2014).

3. T. Flatt, L. Partridge, BMC Biol. 16, 93 (2018).4. C. J. Kenyon, Nature 464, 504–512 (2010).5. C. López-Otín, M. A. Blasco, L. Partridge, M. Serrano,

G. Kroemer, Cell 153, 1194–1217 (2013).6. L. Partridge, J. Deelen, P. E. Slagboom, Nature 561, 45–56 (2018).7. A. Larbi et al., Physiology 23, 64–74 (2008).8. J. Nikolich-Žugich, Nat. Immunol. 19, 10–19 (2018).9. G. Pawelec, Exp. Gerontol. 105, 4–9 (2018).10. B. C. Sheldon, S. Verhulst, Trends Ecol. Evol. 11, 317–321 (1996).11. P. Schmid-Hempel, Evolutionary Parasitology: The Integrated

Study of Infections, Immunology, Ecology, and Genetics(Oxford Univ. Press, 2011).

12. A. Peters, K. Delhey, S. Nakagawa, A. Aulsebrook, S. Verhulst,Ecol. Lett. 10.1111/ele.13343 (2019).

13. E. R. Morgan, E. J. Milner-Gulland, P. R. Torgerson,G. F. Medley, Trends Ecol. Evol. 19, 181–188 (2004).

14. I. M. Cattadori, D. T. Haydon, P. J. Hudson, Nature 433,737–741 (2005).

15. J. Charlier, M. van der Voort, F. Kenyon, P. Skuce,J. Vercruysse, Trends Parasitol. 30, 361–367 (2014).

16. GBD 2015 DALYs and HALE Collaborators, Lancet 388,1603–1658 (2016).

17. R. M. Maizels, M. Yazdanbakhsh, Nat. Rev. Immunol. 3,733–744 (2003).

18. N. Harris, W. C. Gause, Trends Immunol. 32, 80–88 (2011).19. K. M. McRae, M. J. Stear, B. Good, O. M. Keane, Parasite

Immunol. 37, 605–613 (2015).20. L. Cheynel et al., Sci. Rep. 7, 13700 (2017).21. J. Bethony et al., Clin. Infect. Dis. 35, 1336–1344 (2002).22. P. Smith, D. W. Dunne, P. G. Fallon, Eur. J. Immunol. 31,

1495–1502 (2001).23. N. E. Humphreys, R. K. Grencis, Infect. Immun. 70, 5148–5157 (2002).24. S. A. Babayan, A. Sinclair, J. S. Duprez, C. Selman, Sci. Rep.

8, 3802 (2018).25. T. H. Clutton-Brock, J. M. Pemberton, Eds., Soay Sheep:

Dynamics and Selection in an Island Population(Cambridge Univ. Press, 2004).

26. A. D. Hayward et al., Exp. Gerontol. 71, 56–68 (2015).27. K. Wilson, B. T. Grenfell, J. G. Pilkington, H. E. G. Boyd,

F. M. Gulland, in Soay Sheep: Dynamics and Selection in anIsland Population, T. H. Clutton-Brock, J. M. Pemberton, Eds.(Cambridge Univ. Press, 2004), pp. 17–51.

28. D. H. Nussey et al., Proc. Biol. Sci. 281, 20132931 (2014).29. R. L. Watson et al., Ecol. Evol. 6, 8695–8705 (2016).30. A. M. Sparks et al., Am. Nat. 192, 745–760 (2018).31. J. G. A. Martin, M. Festa-Bianchet, Ecol. Lett. 14, 576–581 (2011).32. O. R. Jones et al., Nature 505, 169–173 (2014).33. A. D. Hayward et al., PLOS Biol. 12, e1001917 (2014).

ACKNOWLEDGMENTS

We are grateful to all those involved in the long-term studyof Soay sheep on St. Kilda; J. Hadfield, A. Phillimore, andJ. Pick for statistical advice and discussions; and A. Graham,A. Hayward, L. Kruuk, and R. Maizels for constructivecomments on the manuscript. Thanks to the NationalTrust for Scotland for permission to work on St. Kilda;QinetiQ and Kilda Cruises for logistical support in the field;and D. Bartley, A. Morrison, and R. Maizels for provision ofnematode larvae. Funding: UK Natural Environment ResearchCouncil, Biological and Biomedical Sciences ResearchCouncil, Medical Research Council, The Wellcome Trust(204052/Z/16/Z), and Rural and Environment Science andAnalytical Services Division of the Scottish government.Author contributions: H.F., T.N.M., and D.H.N. designed thestudy; J.G.P. and J.M.P. collected the samples, life historydata, and managed the long-term study; A.M.S., K.W., andR.S. conducted the antibody assays in the laboratory; H.F. andF.B. analyzed the data; H.F. and D.H.N. wrote the manuscriptwith input from all co-authors. Competing interests: Theauthors declare no competing interests. Data and materialsavailability: The data supporting the results are available inthe supplementary materials.

SUPPLEMENTARY MATERIALS

science.sciencemag.org/content/365/6459/1296/suppl/DC1Materials and MethodsFigure S1Tables S1 to S6References (34–52)Data S1

7 January 2019; accepted 30 July 201910.1126/science.aaw5822

Froy et al., Science 365, 1296–1298 (2019) 20 September 2019 3 of 3

Fig. 2. Effects of anti–T. circumcinctaIgG, body weight, and fecal eggcount (FEC) on overwinter survivalprobability in adult Soay sheep.Regression coefficients (median of theposterior distribution with 95%credible intervals) reflect independenteffects on survival, accounting for thecovariance among these traits atdifferent hierarchical levels. Effects areshown for the within-individual(dark gray circles), among-individual(black triangles), and among-year(gray squares) associations with sur-vival. Within-individual deviation inIgG-Tc was predictive of survivalprobability, independent of thewithin- and among-individual variancein body weight and FEC. Effects were estimated from a multivariate model of IgG-Tc, weight (bothGaussian), FEC (Poisson), and survival probability (threshold) (see materials and methods; table S5).IgG-Tc and weight were standardized before inclusion in the model (mean = 0, SD = 1).

RESEARCH | REPORT

Corrected 13 December 2019. See full text. on A

pril 1, 2021

http://science.sciencemag.org/

Dow

nloaded from

http://science.sciencemag.org/content/365/6459/1296/suppl/DC1http://science.sciencemag.org/

Senescence in immunity against helminth parasites predicts adult mortality in a wild mammalH. Froy, A. M. Sparks, K. Watt, R. Sinclair, F. Bach, J. G. Pilkington, J. M. Pemberton, T. N. McNeilly and D. H. Nussey

originally published online September 19, 2019DOI: 10.1126/science.aaw5822 (6459), 1296-1298.365Science

, this issue p. 1296; see also p. 1244Scienceincluding humans, and may thus become an increasing burden on health with age.reduces a sheep's chances of surviving the winter. Helminths are an important component of many natural systems,

whichfrom 800 known individuals that have been left to run wild and unmanaged. Resistance declines as the sheep age, Atlantic island of St. Kilda (see the Perspective by Gaillard and Lemaître). They used a library of 2000 blood samplesmeasured an immune marker of resistance to infection by worm parasites (helminths) in Soay sheep off the remote

et al.Infection, immunity, and demography are rarely measured simultaneously, despite being intertwined. Froy The decline of resistance in old age

ARTICLE TOOLS http://science.sciencemag.org/content/365/6459/1296

MATERIALSSUPPLEMENTARY http://science.sciencemag.org/content/suppl/2019/09/18/365.6459.1296.DC1

CONTENTRELATED

http://stm.sciencemag.org/content/scitransmed/7/286/286re4.fullhttp://stm.sciencemag.org/content/scitransmed/11/483/eaau2086.fullhttp://science.sciencemag.org/content/sci/365/6459/1244.full

REFERENCES

http://science.sciencemag.org/content/365/6459/1296#BIBLThis article cites 47 articles, 3 of which you can access for free

PERMISSIONS http://www.sciencemag.org/help/reprints-and-permissions

Terms of ServiceUse of this article is subject to the

is a registered trademark of AAAS.ScienceScience, 1200 New York Avenue NW, Washington, DC 20005. The title (print ISSN 0036-8075; online ISSN 1095-9203) is published by the American Association for the Advancement ofScience

Science. No claim to original U.S. Government WorksCopyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of

on April 1, 2021

http://science.sciencem

ag.org/D

ownloaded from

http://science.sciencemag.org/content/365/6459/1296http://science.sciencemag.org/content/suppl/2019/09/18/365.6459.1296.DC1http://science.sciencemag.org/content/sci/365/6459/1244.fullhttp://stm.sciencemag.org/content/scitransmed/11/483/eaau2086.fullhttp://stm.sciencemag.org/content/scitransmed/7/286/286re4.fullhttp://science.sciencemag.org/content/365/6459/1296#BIBLhttp://www.sciencemag.org/help/reprints-and-permissionshttp://www.sciencemag.org/about/terms-servicehttp://science.sciencemag.org/