Content uploaded by Alexander Igoshin
Author content
All content in this area was uploaded by Alexander Igoshin on Apr 09, 2024
Content may be subject to copyright.
Influence of breed and environment
on leukocyte telomere length in cattle
N.S. Yudin 1#, A.V. Igoshin 1#, G.A. Romashov1, A.A. Martynov2, D.M. Larkin 3
1 Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia
2 Arctic State Agrotechnological University, Yakutsk, Republic of Sakha (Yakutia), Russia
3 Royal Veterinary College, University of London, London, United Kingdom
dlarkin@rvc.ac.uk
Abstract. High milk yield is associated with reduced longevity in high-producing dairy cattle breeds. Pre-term cull-
ing leads to high replacement heifer demand and economic losses for the dairy industry. Selection for this trait is
limited because of low heritability and difficulties in phenotype measurement. Telomeres are elements found at the
ends of chromosomes, consisting of repetitive DNA sequences, several thousand base pairs in length, coupled with
nucleoprotein complexes. Eventually, in humans and most other animals, telomere length reduces with age. When
telomeric DNA is truncated to a critical length, cell ageing, cell cycle arrest, and apoptosis are induced. As a result,
telomere length can be considered as a predictor of health risks and an individual’s lifespan. The leukocyte telomere
length may be used as a proxy phenotype of productive lifespan to improve cattle selection. Our objectives were to
assess the eects of breed and breed group (dairy vs. beef) on the leukocyte telomere length and to estimate the ef-
fect of cold climate on this trait in Kalmyk cattle populations from the South (Rostov Oblast) and Far North (Republic
of Sakha) regions of Russia. The leukocyte telomere lengths were estimated computationally from whole-genome
resequencing data. We leveraged data on leukocyte telomere length, sex, and age of 239 animals from 17 cattle
breeds. The breed factor had a significant eect on leukocyte telomere length across our sample. There was no dif-
ference in leukocyte telomere length between dairy and beef groups. The population factor had a significant eect
on leukocyte telomere length in Kalmyk animals. In conclusion, we found that breed, but not breed group (dairy vs.
beef), was significantly associated with leukocyte telomere length in cattle. Residence in colder climates was asso-
ciated with longer leukocyte telomere length in Kalmyk breed cattle.
Key words: longevity; selection; cattle; breed; dairy; beef; environment; cold climate; leukocyte telomere length.
For citation: Yudin N.S., Igoshin A.V., Romashov G.A., Martynov A.A., Larkin D.M. Influence of breed and environment
on leukocyte telomere length in cattle. Vavilovskii Zhurnal Genetiki i Selektsii = Vavilov Journal of Genetics and Breeding.
2024;28(2):190-197. DOI 10.18699/vjbg-24-23
Влияние породы и среды на длину теломер лейкоцитов
у крупного рогатого скота
Н.С. Юдин 1#, А.В. Игошин 1#, Г.А. Ромашов1, А.А. Мартынов2, Д.М. Ларкин 3
1 Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук, Новосибирск, Россия
2 Арктический государственный агротехнологический университет, Якутск, Россия
3 Королевский ветеринарный колледж, Лондон, Великобритания
dlarkin@rvc.ac.uk
Аннотация. Высокие удои молока сопряжены с сокращением продолжительности жизни у высокопродук-
тивных молочных пород скота. Преждевременная выбраковка приводит к значительным экономическим по-
терям в молочном животноводстве и увеличению потребности в ремонтных телках. Отбор по этому признаку
затруднен из-за низкой наследуемости и сложности измерения данного фенотипа. Теломеры – это структу-
ры, находящиеся на концах хромосом, состоящие из повторяющихся последовательностей ДНК длиной в не-
сколько тысяч пар оснований, связанных с нуклеопротеиновыми комплексами. У людей и большинства дру-
гих животных длина теломер уменьшается с возрастом. Когда теломерная ДНК сокращается до критической
длины, индуцируются процессы старения клеток, остановки клеточного цикла и апоптоза. В результате длину
теломер можно рассматривать как предиктор рисков для здоровья и продолжительности жизни индивида.
Длина теломер лейкоцитов может быть использована в качестве суррогатного фенотипа для признака про-
дуктивного долголетия для улучшения селекции крупного рогатого скота. Целью нашей работы было – оце-
нить влияние породы и направления продуктивности (молочное или мясное) на длину теломер лейкоцитов, а
также проанализировать влияние холодного климата на этот признак в популяциях крупного рогатого скота
калмыцкой породы на Юге (Ростовская область) и Крайнем Севере (Республика Саха) России. Измерение дли-
ны теломер лейкоцитов осуществлено с помощью компьютерных методов на основе данных полногеномного
© Yudin N.S., Igoshin A.V., Romashov G.A., Martynov A.A., Larkin D.M., 2024
This work is licensed under a Creative Commons Attribution 4.0 License
# These authors contributed equally to this work
ГЕНЕТИКА ЖИВОТНЫХ
Оригинальное исследование
Вавиловский журнал генетики и селекции
Vavilov Journal of Genetics and Breeding. 2024;28(2):190-197
DOI 10.18699/vjgb-24-23
Влияние породы и среды на длину теломер лейкоцитов
у крупного рогатого скота
Н.С. Юдин, А.В. Игошин, Г.А. Ромашов
А.А. Мартынов, Д.М. Ларкин
2024
28 • 2
191
ГЕНЕТИКА ЖИВОТНЫХ / ANIMAL GENETICS
ресеквенирования. Мы использовали данные о длине теломер лейкоцитов, половой принадлежности и воз-
расте 239 животных, относящихся к 17 породам крупного рогатого скота. Фактор породы оказывает суще-
ственное влияние на длину теломер лейкоцитов в нашей выборке. Достоверных различий в длине теломер
лейкоцитов между молочными и мясными группами нами не выявлено. Значительное влияние на длину те-
ломер лейкоцитов у животных калмыцкой породы оказывает фактор популяции. Таким образом, мы обнару-
жили, что именно порода, но не направление продуктивности (молочное или мясное), достоверно влияла на
длину теломер лейкоцитов у крупного рогатого скота. Разведение в более холодном климате было ассоцииро-
вано с большей длиной теломер лейкоцитов у крупного рогатого скота калмыцкой породы.
Ключевые слова: долголетие; селекция; крупный рогатый скот; молочный; мясной; холодный климат; длина
теломер лейкоцитов.
Introduction
High milk production correlates with poor longevity in high-
producing cattle breeds, primarily Holstein Friesian (Hu et
al., 2021). Pre-term culling leads to high replacement heifer
demand and economic losses for the dairy industry (Grandl
et al., 2019). There is a need to improve the longevity traits
of dairy cattle. However, selection for these traits is limited
because of low heritability and diculties in phenotype mea-
surement (Zhang H. et al., 2021).
Telomeres are elements found at the ends of chromosomes,
consisting of repetitive DNA sequences, several thousand base
pairs in length, coupled with nucleoprotein complexes (Jenner
et al., 2022). They protect the chromosomes from degrada-
tion and inhibit aberrant rearrangements during cell division
(Monaghan, Ozanne, 2018). Telomeres become shorter with
every cell division due to the end replication problem (Chakra-
varti et al., 2021) but can be maintained through telomerase
activity (Schrumpfová, Fajkus, 2020) and shelterin complex
(de Lange, 2018). Eventually, in humans and most other ani-
mals, telomere length reduces with age (Blackburn et al., 2015;
Whittemore et al., 2019). When telomeric DNA is truncated
to a critical length, cell ageing, cell cycle arrest, and apoptosis
are induced (Chakravarti et al., 2021; López-Otín et al., 2023).
As a result, telomere length can be considered as a predictor
of health risks and an individual’s lifespan. Telomere length
is correlated with many age-related conditions in humans
(Armanios, 2022; Rossiello et al., 2022) and reduced life ex-
pectancy in humans and other species (Wilbourn et al., 2018;
Liu et al., 2019; Crocco et al., 2021).
Telomeres in cattle shorten with age, similar to most other
animals (Miyashita et al., 2002). Adult Holstein dams with
short telomeres are more likely to be culled than dams with
long telomeres (Brown et al., 2012). Productive lifespan in
Holsteins was correlated with telomere length at birth (Ilska-
Warner et al., 2019), at the age of one year (Seeker et al.,
2018a), as well as telomere attrition rate (Seeker et al., 2021).
The telomere length in the Agerolese breed, having a long
lifespan, was signicantly higher than that in the Holstein
breed of the same age (Iannuzzi et al., 2022). Therefore,
telomere length may be used as a proxy trait of lifespan and
health to improve cattle selection.
Telomere length in cattle is a complex trait controlled by
both genetics and environment. However, it is still unclear to
what extent these factors inuence this trait. A recent meta-
analysis of the heritability of telomere length showed a mode-
rate mean heritability of this trait (0.45) in 18 vertebrate species
(Chik et al., 2022). Estimates of the heritability of telomere
length, even in a single species (human), may range from 0.36
(Andrew et al., 2006) to 0.70 (Broer et al., 2013). This vari-
ability in estimates appears to be due to dierent research
me thodologies. For example, in most studies, parents and
o spring are of dierent ages. In statistical analyses, age is
counted as a covariate, but this implies a linear relationship
between telomere length and age, which is not always the case
(Dugdale, Richardson, 2018).
The inuence of environmental factors on telomere length
has been well studied in human epidemiological studies. For
example, a negative correlation was found between telomere
length and emotional stress (Law et al., 2016), Western pat-
tern diet (Rae et al., 2017), cigarette smoking (Astuti et al.,
2017), and environmental chemicals (Zhang X. et al., 2013).
In birds, short telomeres or a high rate of telomere shorten-
ing have been associated with malaria infection (Asghar et
al., 2016), increased brood size (Reichert et al., 2014), early
postnatal stress (Herborn et al., 2014) and sibling competition
(Mizutani et al., 2016).
Heritability estimates of leukocyte telomere length in Hol-
stein cattle ranged from 0.32 to 0.47 (Seeker et al., 2018a, b).
Fourteen candidate genes at birth and nine at rst lactation
were associated with this trait in this breed using a genome-
wide association study (Ilska-Warner et al., 2019). Our ge-
nome-wide association study of seventeen cattle breeds re-
vealed several SNPs associated with bovine telomere length.
We also conrmed the eects of loci reported by previous
studies (Igoshin et al., 2023). Mastitis (Ilska-Warner et al.,
2019), bovine leukaemia virus infection (Szczotka et al.,
2019), oxidative stress (Ribas-Maynou et al., 2022), parturi-
tion and raising the rst calf (O’Daniel et al., 2023), lameness
(Ilska-Warner et al., 2019), and lactation (Laubenthal et al.,
2016) have been found to be associated with cattle telomere
length. The management of the farm and genetics are herd-
related factors that can signicantly aect telomere length
(Brown et al., 2012). However, the question remains unan-
swered: to what extent is telomere length in cattle determined
by breed and inuenced by environmental stressors, such as
weather conditions?
There are two studies on the association of the animal breed
and telomere length in cattle (Tilesi et al., 2010; Iannuzzi et
al., 2022). Both studies found dierences in telomere lengths
between the two cattle breeds in the same tissues. However,
it is unclear how widespread this phenomenon is across mul-
tiple cattle breeds with dierent phylogenetic origins and
ecogeographic breeding conditions. P. Kordowitzki et al.
hy pothesized that severely disturbed energy balance in high-
producing dairy cows eventually leads to decreased regene-
rative capacity and premature senescence, which can be
N.S. Yudin, A.V. Igoshin, G.A. Romashov
A.A. Martynov, D.M. Larkin
192 Вавиловский журнал генетики и селекции / Vavilov Journal of Genetics and Breeding • 2024 • 28 • 2
Influence of breed and environment
on leukocyte telomere length in cattle
assessed by telomere length (Kordowitzki et al., 2021). The
fraction of short telomeres in PBMCs of the high-producing
Holstein-Friesian breed was higher than in the dual-purpose
Polish Red breed, but this observation was not supported by
a statistical test signicance. Therefore, it remains unclear
whether dierent breeds of cattle (dairy vs. beef) exhibit va-
riation in telomere length.
Seeker et al. suggested that heat may be an environmental
stressor capable of causing telomere attrition (Seeker et al.,
2021). They found a strong correlation between maximum
summer temperature and telomere attrition in Holstein-
Friesian cattle. Heat stress during gestation also aected the
telomere length in newborn Holstein calves. A higher median
temperature-humidity index during gestation resulted in calves
born with shorter telomere lengths (Meesters et al., 2023).
There are, however, no studies that investigate the inuence
of cold weather on telomere length in cattle. A single human
study showed that prenatal temperature exposure below 5 °C
was associated with longer telomere length in newborn babies
(Martens et al., 2019).
There are only two native beef cattle breeds in Russia: Kal-
myk and its derivative Kazakh Whiteheaded breeds. It is be-
lieved that the Kalmyk cattle originated in Northwest China
(Dzungaria) and was brought to Russia, to the Volga area, by
migrating nomadic tribes in the seventeenth century (Dmit-
riev, Ernst, 1989). The Kalmyk breed was created under harsh
conditions: the icy wind in winter or the hot sun in summer,
frequent epizootics, etc. The specic traits of the Kalmyk
breed include high viability, adaptation to the harsh climate,
resistance to infections, long lifespan, thickening of the epi-
dermis at the expense of the dermis in winter, abundance of
sebaceous and sweat glands in the skin compared to other
breeds (Dmitriev, Ernst, 1989). In Russia, the Kalmyk beef
herd is mainly found in two regions: the Republic of Kalmy-
kia and Rostov Oblast (Kayumov et al., 2014). This breed has
also been reared in the Republic of Sakha (Yakutia) since 2013
when about 200 Kalmyk cattle animals were imported from
the Republic of Kalmykia (Sleptsov, Machakhtyrova, 2019).
Yakutia has an extreme and severe climate, with the average
winter temperature below −35 °C.
The objectives of our study were (1) to assess the eects
of breed and breed group (dairy vs. beef) on the leukocyte
telomere length in the sample of 239 animals from 17 cattle
breeds and (2) to estimate the eect of cold climate on this trait
in Kalmyk cattle populations from the South and Far North
regions of Russia. We hypothesized that high milk yield or
extreme cold weather may be stress factors that may have led
to a change in telomere length in cattle.
Materials and methods
Samples. In this work, we leveraged data on leukocyte telo-
mere length, sex, and age of 239 animals from 17 cattle breeds
used in our previous study (Igoshin et al., 2023). The leukocyte
telomere lengths have been estimated computationally from
whole-genome resequencing data using TelSeq software (Ding
et al., 2014), which is a frequently used program for this pur-
pose and which has been conrmed by multiple experimental
techniques (Ding et al., 2014; Cook et al., 2016; Pinese et al.,
2020; Taub et al., 2022; Zhang D. et al., 2022). The details of
the estimation procedure can be found in our previous work
(Igoshin et al., 2023).
The breeds investigated are dairy (Russian Black Pied,
Holstein, Kholmogory, Red Steppe, Yaroslavl), beef (Charo-
lais, Hereford, Kalmyk, Kazakh Whiteheaded, Wagyu), and
dual-purpose (Alatau, Bestuzhev, Buryat, Kostroma, Tagil,
Ukrainian Grey, Yakut) (Dunin, Dankvert, 2013; Lhasaranov,
2020). Among 30 individuals of the Kalmyk cattle breed
(Supplementary Material 1)1, one group of animals (n = 10)
was reared in Rostov Oblast (Mechetny settlement), while the
other (n = 20) was from the Republic of Sakha (Kyuyore lyakh
settlement). The climatic conditions in these locations dier
substantially (see the Table). All the Kalmyk animals from
both locations were raised in a stall-pasture system.
Population structure. Even in the absence of selection,
a founder eect or, more broadly, genetic drift could lead to
genetic dierentiation between two isolated populations of
common origin. To ensure that two populations of the Kal-
myk breed are genetically indistinguishable, we performed
the principal component analysis using PLINK v.1.9 (Purcell
et al., 2007) (--pca option) and the analysis of population
structure using fastSTRUCTURE v1.0 (Raj et al., 2014). The
fastSTRUCTURE program was run with K ranging from K = 2
to K = 8. The resulting cluster memberships were visualized
with PONG v.1.5 software (Behr et al., 2016). For both me-
thods, we used an LD-pruned (PLINK: --indep-pairwise 5000
100 0.1) dataset containing genotypes of 20,184 SNPs in
116 animals (Kalmyk animals and individuals having SRA ID
from Supplementary Material 1).
Statistical analysis. Like in many other studies, the distri-
bution of LTL in our work was skewed. If not corrected, this
violates the assumptions of parametric tests, thus aecting
statistical power (Lantz, 2013). Therefore, associations with
LTL were tested by using log-transformed LTL values (e. g.
Leung et al., 2014; Lynch et al., 2016). To nd out whether
a breed factor contributes to LTL variation in cattle, we used
1 Supplementary Materials 1–6 are available at:
https://vavilovj-icg.ru/download/pict-2024-28/appx10.pdf
The climatic conditions for the sampling locations in Rostov Oblast and the Republic of Sakha
(according to https://climatecharts.net (Zepner et al., 2021), accessed on 30 August 2023)
Location Coordinates Mean January
temperature, °C
Mean July
temperature, °C
Mean annual
temperature, °C
Precipitation sum,
mm
Mechetny settlement
(Rostov Oblast)
48°03’54”N,
40°38’23”E
–4.4 23.7 9.8 508.7
Kyuyorelyakh settlement
(Republic of Sakha)
62°34’17”N,
126°50’26”E
–37.2 18.0 –9.1 312.7
Влияние породы и среды на длину теломер лейкоцитов
у крупного рогатого скота
Н.С. Юдин, А.В. Игошин, Г.А. Ромашов
А.А. Мартынов, Д.М. Ларкин
2024
28 • 2
193
ГЕНЕТИКА ЖИВОТНЫХ / ANIMAL GENETICS
ANOVA (“aov” R function) with log-transformed LTLs
(log10(LTLs)) as a response variable and breed as a factor va-
riable, accounting for age and sex: aov(logLTL ~ Age + Sex +
Breed). To nd out which breeds signicantly dier from each
other, we additionally performed a standard ANOVA post hoc
test – Tukey’s HSD test utilising the “glht” function from the
“multcomp” R package (Hothorn et al., 2008). Also, we com-
bined beef and dairy breeds into two groups and tested for a
dierence between them: aov(logLTL ~ Age + Sex + Group).
As all the Kalmyk individuals used were dams, the test for
dierences between this breed’s populations was conducted
by accounting only for age: aov(logLTL ~ Age + Population).
For statistically signicant variables we estimated the va-
riance explained (η2) using the “eta_squared” function from
the “eectsize” R package (Ben-Shachar et al., 2020) with the
“partial = TRUE” option.
Preparing data for visualization and descriptive sta-
tistics. As conrmed in our study, telomere length typically
decreases with age (Spearman’s ρ = –0.305, p = 1.58 × 10–6
for raw and log-transformed LTLs) (Supplementary Mate-
rial 2). Therefore, for boxplot visualization and descriptive
statistics, we calculated the log10(LTL) values expected given
the constant age. For this purpose, we tted a regression model
(“lm” R function) with logLTL as the response variable, and
age, sex (coded by 0/1) and breed (16 covariates coded by
0/1) variables as predictors. As a result, we obtained regres-
sion parameters (intercept and slopes for each predictor) and
residuals. For each animal, we summed up: the intercept, the
animal’s residual, and products of each predictor value and
its respective slope. For the age predictor, however, actual
values were substituted by the average value of 4.5 years. The
resulting values represent the expectation for logLTL given
the constant age of 4.5 years. These age-ad justed log10(LTLs)
and their corresponding values in kilobases (here after “age-
adjusted LTLs”) are shown in Supplementary Material 1. The
descriptive statistics for breeds can be found in Supplementary
Material 3.
Results
The statistical analysis shows that breed factor has a signi-
cant ( p = 6.12 × 10–15, η2 = 0.37) eect on leukocyte telomere
length across our sample of 239 individuals (see Figure, a).
Tukey’s HSD test showed signicant dierences for 28 breed
pairs (Supplementary Material 4). At the same time, there is no
signicant dierence in LTL between dairy and beef groups
( p = 0.0748) (see Figure, b).
The statistical testing performed for the Kalmyk breed
shows that the population factor has a signicant ( p = 0.0283,
Boxplots illustrating the log-transformed and adjusted for age (expectation at 4.5 years) leukocyte telomere lengths
in(a) dierent breeds; (b) beef and dairy breed groups, and (c) in two populations of the Kalmyk breed.
The p-values designate the statistical significance for dierences between the abovementioned categories. The brown, pink
and light-yellow colours correspond to beef, dual-purpose, and dairy breeds. The numbers at the top of boxplots indicate the
number of animals.
1.8
1.6
1.4
1.2
1.0
0.8
0.6
1.8
1.6
1.4
1.2
1.0
0.8
0.6
1.0
0.9
0.8
Ukrainian Grey
Wagyu
Red Steppe
Alatau
Tagil
Kalmyk
Kostroma
Bestuzhev
Yakut
Charolais
Black Pied
Kazakh Whiteheaded
Holstein
Yaroslavl
Kholmogory
Hereford
Buryat
Beef
a b c
10
10
20
20
12
12
37
17
15
22
12
96
60
19
3
8
4
3
5
30
p = 0.0748 p = 0.0283
Kalmyk
Rostov
Kalmyk
Sakha
Dairy
Age-adjusted log(LTL)
10
N.S. Yudin, A.V. Igoshin, G.A. Romashov
A.A. Martynov, D.M. Larkin
194 Вавиловский журнал генетики и селекции / Vavilov Journal of Genetics and Breeding • 2024 • 28 • 2
Influence of breed and environment
on leukocyte telomere length in cattle
η2 = 0.17) eect on LTL in studied Kalmyk animals, with
the individuals from Rostov Oblast having shorter telomeres
(see Figure, c). The results of the principal component ana-
lysis show that the Rostov and Sakha populations form two
highly overlapping clusters (Supplementary Material 5). Also,
fastSTRUCTURE results suggest that the two Kalmyk po-
pulations are homogeneous and possible genetic dierences
between them do not exceed the level of variation within
other breeds (Supplementary Material 6). Therefore, the LTL
dierences between the two groups are most likely explained
by environmental conditions.
It should also be mentioned that the age variable signi-
cantly aects LTL in all tests: p = 1.46 × 10–6, η2 = 0.10 (testing
for the eect of breed); p = 0.0248, η2 = 0.07 (dairy vs. beef
group); and p = 0.0038, η2 = 0.27 (Kalmyk Sakha vs. Kalmyk
Rostov). However, the sex factor has no signicant eect on
LTL either in the test for breed factor ( p = 0.205) or in the
test for the factor of breed group ( p = 0.8752).
Discussion
The primary aim of this study was to investigate the correlation
between the breed type and leucocyte telomere length (LTL)
in cattle. Our additional goal was to check the eect of the
environment (e. g., colder climate) on the LTL within popula-
tions of the same breed grown in dierent climates. Based on
the resequencing data of 17 cattle breeds, our ndings indicate
that the breed factor has a signicant impact on LTL. These
results align with earlier studies that reported LTL dierences
in pairwise comparisons between cattle breeds (Tilesi et al.,
2010; Iannuzzi et al., 2022). We also found evidence for an
association between LTL and dierences in climatic conditions
for a single cattle breed reared in dierent regions of Russia.
It was shown in our analysis that the breed factor contributes
more to total LTL variation compared to age. The possible
practical implication for this could be the use of breeds cha-
racterised by long telomeres in crossbreeding programs aimed
to improve telomere-length-associated phenotypes in cattle.
Apart from cattle, studies are reporting LTL dierences
between Caenorhabditis elegans strains (Cook et al., 2016),
outbred populations and inbred strains of mice (Mus musculus
and Peromyscus leucopus) (Manning et al., 2002), and dog
breeds (Fick et al., 2012). These reports suggest the existence
of a genetic basis for such variability. Based on heritability
estimates for LTL in Holsteins (0.32–0.47) (Seeker et al.,
2018a, b), we propose that genetic factors may largely explain
inter-breed dierences observed in our study.
Herein we compared the LTL in dairy and beef breeds. The
results however, did not reveal any statistically signicant
dierence between these two groups. This nding is con-
sistent with a previous study that compared LTLs between
dairy and dual-purpose cattle breeds, which also showed no
dierence (Kordowitzki et al., 2021). Our study focused on
distinct groups of cattle breeds, specically dairy and beef,
covering a wider range of genetics than the previous study.
Also, each production breed type was represented by ve
breeds. Therefore, the results reported herein could provide
stronger support for the lack of LTL dierences between the
cattle breed types. Our results are also consistent with similar
studies done in other domestic species, e. g., dogs, where no
dierence in LTL was reported for breed groups (working,
herding, hunting) (Fick et al., 2012). It appears that comple-
mentary contributions of many factors aecting a particular
breed (e. g. genetic makeup, management practices, veterina-
ry care, climate conditions, etc.) have a greater inuence on
the LTL than physiological features associated with dierent
pro duction types. This result suggests that the selection for
telomere-length-associated traits will probably not lead to
substantial changes in milk or meat yields.
To investigate the possible eects of environments on
telomere lengths of the same cattle breed, we compared the
LTLs between two populations of the Kalmyk cattle reared
in dierent climatic conditions. We observed a signicant
dierence in agreement with a previous human study show-
ing an association between prenatal cold exposure and longer
blood telomere length in newborns (Martens et al., 2019).
Indeed, longer telomere lengths detected in animals from the
Sakha Republic with colder climates compared to the control
population from Rostov Oblast imply that there could be a
mechanism of telomere maintenance in colder climates in
cattle. In ectotherms, however, there are reports that at cooler
conditions telomere shortening happens during development
(Friesen et al., 2022; Burraco et al., 2023), but other authors
did not conrm this observation (McLennan et al., 2018).
In bat species, Myotis myotis, average and minimum tem-
peratures, rainfall and wind speed during the spring when
bats emerge from hibernation, give birth and rear young were
associated with higher telomere attrition (Foley et al., 2020).
The authors, however, did not report which variable is the
driver for telomere length change. The comparison of telomere
length between two species of rodents hibernating at either 3
or 14 °C revealed that individuals hibernating at the warmer
temperature had longer telomeres than individuals hibernating
at the colder temperature (Nowack et al., 2019). The authors
hypothesized that the observed eect was not related to cold
climate, but rather was associated with restoration of telomere
length during frequent arousals when the body temperature
returns to normal values.
The mechanisms by which cold climate impacts leukocyte
telomere length in cattle remain unclear. On the one hand,
cold exposure may inhibit telomere shortening, since low
temperature reduces the rate of cell proliferation in mamma-
lian cells (Kanagawa et al., 2006; Fulbert et al., 2019). On the
other hand, cold exposure may induce telomere elongation by
inuencing the components of the telomerase complex. It was
shown that cold-inducible RNA-binding protein (CIRP) was
essential for telomere maintenance at hypothermia conditions
in vitro by regulating both reverse transcriptase TERT and the
RNA subunit TERC in the telomerase core complex (Zhang Y.
et al., 2016). The transcription of telomeric repeat-containing
RNAs (TERRAs), which are associated with telomere stabil-
ity, was induced in mice exposed to cold (Galigniana et al.,
2020).
One could ask if there is an optimal ambient temperature
at which the LTL in cattle would be the longest. The few
studies on the eect of ambient temperature on the LTL of
endothermic mammals do not allow us to answer this question
unambiguously. Extremely low or high ambient temperatures
lead to hypo- and hyperthermia when the body temperature
deviates substantially below and above the narrow limits of
the regulated range, i. e., cause stress. The inuence of a large
Влияние породы и среды на длину теломер лейкоцитов
у крупного рогатого скота
Н.С. Юдин, А.В. Игошин, Г.А. Ромашов
А.А. Мартынов, Д.М. Ларкин
2024
28 • 2
195
ГЕНЕТИКА ЖИВОТНЫХ / ANIMAL GENETICS
number of stressors, including extreme environmental fac-
tors, is known to be associated with shorter telomeres or an
increased rate of telomere shortening (Chatelain et al., 2020;
Lin, Epel, 2022).
Indirect information on the eect of moderate cold on LTL,
when body temperature remains within the normal range,
could be obtained from studies of the eect of body tempera-
ture on the ageing process. On the one hand, in endotherms,
a small decrease in body temperature is associated with an
increase in life expectancy (Conti et al., 2006; Carrillo, Flouris,
2011). On the other hand, in some cases, there is an inverse
relationship (Zhao et al., 2022). For example, human females
tend to have a longer life expectancy than males, but their body
temperature is higher (Waalen, Buxbaum, 2011). The mecha-
nisms that control the relationship between body temperature
and life expectancy involve not only a decrease in metabolic
rate when the temperature declines, but also neuroendocrine
processes that indirectly aect a variety of physiological
responses when temperature changes. Therefore, the optimal
limits of ambient temperature at which the LTL in cattle will
be longest could exist, but this question requires further study.
Conclusion
In conclusion, we found that breed, but not breed group (dairy
vs. beef ), signicantly inuenced leukocyte telomere length
in cattle. Residence in colder climates was associated with
longer leukocyte telomere length in the Kalmyk cattle breed.
Our results add to the evidence regarding the inuence of
breed origin and cold climate on this trait in farm animals.
References
Andrew T., Aviv A., Falchi M., Surdulescu G.L., Gardner J.P., Lu X.,
Kimura M., Kato B.S., Valdes A.M., Spector T.D. Mapping genetic
loci that determine leukocyte telomere length in a large sample of
unselected female sibling pairs. Am. J. Hum. Genet. 2006;78(3):
480-486. DOI 10.1086/500052
Armanios M. The role of telomeres in human disease. Annu. Rev.
Genomics Hum. Genet. 2022;23:363-381. DOI 10.1146/annurev-
genom-010422-091101
Asghar M., Palinauskas V., Zaghdoudi-Allan N., Valkiūnas G., Mu-
khin A., Platonova E., Färnert A., Bensch S., Hasselquist D. Paral-
lel telomere shortening in multiple body tissues owing to malaria
infection. Proc. Biol. Sci. 2016;283(1836):20161184. DOI 10.1098/
rspb.2016.1184
Astuti Y., Wardhana A., Watkins J., Wulaningsih W.; PILAR Research
Network. Cigarette smoking and telomere length: A systematic re-
view of 84 studies and meta-analysis. Environ. Res. 2017;158:480-
489. DOI 10.1016/j.envres.2017.06.038
Behr A.A., Liu K.Z., Liu-Fang G., Nakka P., Ramachandran S. pong:
fast analysis and visualization of latent clusters in population ge-
netic data. Bioinformatics. 2016;32(18):2817-2823. DOI 10.1093/
bioinformatics/btw327
Ben-Shachar M.S., Lüdecke D., Makowski D. eectsize: Estimation
of eect size indices and standardized parameters. J. Open Source
Softw. 2020;5(56):2815. DOI 10.21105/joss.02815
Blackburn E.H., Epel E.S., Lin J. Human telomere biology: A con-
tributory and interactive factor in aging, disease risks, and protec-
tion. Science. 2015;350(6265):1193-1198. DOI 10.1126/science.
aab3389
Broer L., Codd V., Nyholt D.R., Deelen J., Mangino M., Willemsen G.,
Albrecht E., … Vink J.M., Spector T.D., Slagboom P.E., Mar-
tin N.G., Samani N.J., van Duijn C.M., Boomsma D.I. Meta-ana-
lysis of telomere length in 19,713 subjects reveals high heritability,
stronger maternal inheritance and a paternal age eect. Eur. J. Hum.
Genet. 2013;21(10):1163-1168. DOI 10.1038/ejhg.2012.303
Brown D.E., Dechow C.D., Liu W.S., Harvatine K.J., Ott T.L. Hot
topic: association of telomere length with age, herd, and culling
in lactating Holsteins. J. Dairy Sci. 2012;95(11):6384-6387. DOI
10.3168/jds.2012-5593
Burraco P., Hernandez-Gonzalez M., Metcalfe N.B., Monaghan P.
Ageing across the great divide: tissue transformation, organismal
growth and temperature shape telomere dynamics through the meta-
morphic transition. Proc. Biol. Sci. 2023;290(1992):20222448. DOI
10.1098/rspb.2022.2448
Carrillo A.E., Flouris A.D. Caloric restriction and longevity: eects of
reduced body temperature. Ageing Res. Rev. 2011;10(1):153-162.
DOI 10.1016/j.arr.2010.10.001
Chakravarti D., LaBella K.A., DePinho R.A. Telomeres: history, health,
and hallmarks of aging. Cell. 2021;184(2):306-322. DOI 10.1016/
j.cell.2020.12.028
Chatelain M., Drobniak S.M., Szulkin M. The association between
stressors and telomeres in non-human vertebrates: a meta-analysis.
Ecol. Lett. 2020;23(2):381-398. DOI 10.1111/ele.13426
Chik H.Y.J., Sparks A.M., Schroeder J., Dugdale H.L. A meta-analy-
sis on the heritability of vertebrate telomere length. J. Evol. Biol.
2022;35(10):1283-1295. DOI 10.1111/jeb.14071
Conti B., Sanchez-Alavez M., Winsky-Sommerer R., Morale M.C., Lu-
cero J., Brownell S., Fabre V., Huitron-Resendiz S., Henriksen S.,
Zorrilla E.P., de Lecea L., Bartfai T. Transgenic mice with a reduced
core body temperature have an increased life span. Science. 2006;
314(5800):825-828. DOI 10.1126/science.1132191
Cook D.E., Zdraljevic S., Tanny R.E., Seo B., Riccardi D.D., Nob-
le L.M., Rockman M.V., Alkema M.J., Braendle C., Kammenga J.E.,
Wang J., Kruglyak L., Félix M.A., Lee J., Andersen E.C. The ge-
netic basis of natural variation in Caenorhabditis elegans telomere
length. Genetics. 2016;204(1):371-383. DOI 10.1534/genetics.116.
191148
Crocco P., De Rango F., Dato S., Rose G., Passarino G. Telomere length
as a function of age at population level parallels human survival
curves. Aging (Albany NY ). 2021;13(1):204-218. DOI 10.18632/
aging.202498
de Lange T. Shelterin-mediated telomere protection. Annu. Rev. Genet.
2018;52:223-247. DOI 10.1146/annurev-genet-032918-021921
Ding Z., Mangino M., Aviv A., Spector T., Durbin R. Estimating telo-
mere length from whole genome sequence data. Nucleic Acids Res.
2014;42(9):e75. DOI 10.1093/nar/gku181
Dmitriev N.G., Ernst L.K. (Eds.). Animal Genetics Resources of the
USSR. Rome: Food and Agriculture Organization of the United Na-
tions, 1989
Dugdale H.L., Richardson D.S. Heritability of telomere variation: it is
all about the environment! Philos. Trans. R. Soc. Lond. B Biol. Sci.
2018;373(1741):20160450. DOI 10.1098/rstb.2016.0450
Dunin I.M., Dankvert A.G. (Eds.). Breeds and Types of Farm Animals
in the Russian Federation. Moscow: All-Russia Research Institute of
Animal Breeding, 2013 (in Russian)
Fick L.J., Fick G.H., Li Z., Cao E., Bao B., Heelnger D., Par-
ker H.G., Ostrander E.A., Riabowol K. Telomere length correlates
with life span of dog breeds. Cell Rep. 2012;2(6):1530-1536. DOI
10.1016/j.celrep.2012.11.021
Foley N.M., Petit E.J., Brazier T., Finarelli J.A., Hughes G.M., Touza-
lin F., Puechmaille S.J., Teeling E.C. Drivers of longitudinal telo-
mere dynamics in a long-lived bat species, Myotis myotis. Mol. Ecol.
2020;29(16):2963-2977. DOI 10.1111/mec.15395
Friesen C.R., Wapstra E., Olsson M. Of telomeres and temperature:
Measuring thermal eects on telomeres in ectothermic animals. Mol.
Ecol. 2022;31(23):6069-6086. DOI 10.1111/mec.16154
Fulbert C., Gaude C., Sulpice E., Chabardès S., Ratel D. Moderate hy-
pothermia inhibits both proliferation and migration of human glio-
blastoma cells. J. Neurooncol. 2019;144(3):489-499. DOI 10.1007/
s11060-019-03263-3
N.S. Yudin, A.V. Igoshin, G.A. Romashov
A.A. Martynov, D.M. Larkin
196 Вавиловский журнал генетики и селекции / Vavilov Journal of Genetics and Breeding • 2024 • 28 • 2
Influence of breed and environment
on leukocyte telomere length in cattle
Galigniana N.M., Charó N.L., Uranga R., Cabanillas A.M., Piwien-Pi-
lipuk G. Oxidative stress induces transcription of telomeric repeat-
containing RNA (TERRA) by engaging PKA signaling and cyto-
skeleton dynamics. Biochim. Biophys. Acta Mol. Cell. Res. 2020;
1867(4):118643. DOI 10.1016/j.bbamcr.2020.118643
Grandl F., Furger M., Kreuzer M., Zehetmeier M. Impact of longe vity
on greenhouse gas emissions and protability of individual dairy
cows analysed with dierent system boundaries. Animal. 2019;
13(1):198-208. DOI 10.1017/S175173111800112X
Herborn K.A., Heidinger B.J., Boner W., Noguera J.C., Adam A.,
Daunt F., Monaghan P. Stress exposure in early post-natal life reduc-
es telomere length: an experimental demonstration in a long-lived
seabird. Proc. Biol. Sci. 2014;281(1782):20133151. DOI 10.1098/
rspb.2013.3151
Hothorn T., Bretz F., Westfall P. Simultaneous inference in general
parametric models. Biom. J. 2008;50(3):346-363. DOI 10.1002/
bimj.20081042
Hu H., Mu T., Ma Y., Wang X., Ma Y. Analysis of longevity traits in
Holstein cattle: A review. Front. Genet. 2021;12:695543. DOI
10.3389/fgene.2021.695543
Iannuzzi A., Albarella S., Parma P., Galdiero G., D’Anza E., Pistuc-
ci R., Peretti V., Ciotola F. Characterization of telomere length in
Agerolese cattle breed, correlating blood and milk samples. Anim.
Genet. 2022;53(5):676-679. DOI 10.1111/age.13227
Igoshin A.V., Yudin N.S., Romashov G.A., Larkin D.M. A multibreed
genome-wide association study for cattle leukocyte telomere length.
Genes (Basel). 2023;14(8):1596. DOI 10.3390/genes14081596
Ilska-Warner J.J., Psidi A., Seeker L.A., Wilbourn R.V., Under-
wood S.L., Fairlie J., Whitelaw B., Nussey D.H., Coey M.P., Ba-
nos G. The genetic architecture of bovine telomere length in early
life and association with animal tness. Front. Genet. 2019;10:
1048. DOI 10.3389/fgene.2019.01048
Jenner L.P., Peska V., Fulnečková J., Sýkorová E. Telomeres and their
neighbors. Genes (Basel). 2022;13(9):1663. DOI 10.3390/genes130
91663
Kanagawa T., Fukuda H., Tsubouchi H., Komoto Y., Hayashi S., Fu-
kui O., Shimoya K., Murata Y. A decrease of cell proliferation by
hypothermia in the hippocampus of the neonatal rat. Brain Res.
2006;1111(1):36-40. DOI 10.1016/j.brainres.2006.06.112
Kayumov F.G., Chernomyrdin V.N., Mayevskaya L.A., Surundae-
va L.G., Polskikh S.S. The use of Kalmyk cattle on animal breeding
farms in Russia. Izv. Orenbg. State Agrar. Univ. 2014;5(49):116-119
(in Russian)
Kordowitzki P., Merle R., Hass P.-K., Plendl J., Rieger J., Kaess-
meyer S. Inuence of age and breed on bovine ovarian capillary
blood supply, ovarian mitochondria and telomere length. Cells.
2021;10(10):2661. DOI 10.3390/cells10102661
Lantz B. The impact of sample non-normality on ANOVA and alterna-
tive methods. Br. J. Math. Stat. Psychol. 2013;66(2):224-244. DOI
10.1111/j.2044-8317.2012.02047.x
Laubenthal L., Hoelker M., Frahm J., Dänicke S., Gerlach K., Süde-
kum K.-H., Sauerwein H., Häussler S. Short communication: Telo-
mere lengths in dierent tissues of dairy cows during early and late
lactation. J. Dairy Sci. 2016;99(6):4881-4885. DOI 10.3168/jds.
2015-10095
Law E., Girgis A., Lambert S., Sylvie L., Levesque J., Pickett H. Telo-
meres and stress: promising avenues for research in psycho-onco-
logy. Asia-Pacific J. Oncol. Nurs. 2016;3(2):137-147. DOI 10.4103/
2347-5625.182931
Leung C.W., Laraia B.A., Needham B.L., Rehkopf D.H., Adler N.E.,
Lin J., Blackburn E.H., Epel E.S. Soda and cell aging: associations
between sugar-sweetened beverage consumption and leukocyte telo-
mere length in healthy adults from the National Health and Nutri-
tion Examination Surveys. Am. J. Public Health. 2014;104(12):
2425-2431. DOI 10.2105/AJPH.2014.302151
Lhasaranov B. Pasture animal husbandry in Eastern Siberia. Biomed.
J. Sci. Tech. Res. 2020;31(3):24160-24163. DOI 10.26717/BJSTR.
2020.31.005094
Lin J., Epel E. Stress and telomere shortening: Insights from cellular
mechanisms. Ageing Res. Rev. 2022;73:101507. DOI 10.1016/j.arr.
2021.101507
Liu J., Wang L., Wang Z., Liu J.-P. Roles of telomere biology in cell
senescence, replicative and chronological ageing. Cells. 2019;8(1):
54. DOI 10.3390/cells8010054
López-Otín C., Blasco M.A., Partridge L., Serrano M., Kroemer G.
Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243-
278. DOI 10.1016/j.cell.2022.11.001
Lynch S.M., Peek M.K., Mitra N., Ravichandran K., Branas C., Span-
gler E., Zhou W., Paskett E.D., Gehlert S., DeGranreid C., Reb-
beck T.R., Riethman H. Race, ethnicity, psychosocial factors, and
telomere length in a multicenter setting. PLoS One. 2016;11(1):
e0146723. DOI 10.1371/journal.pone.0146723
Manning E.L., Crossland J., Dewey M.J., Van Zant G. Inuences of in-
breeding and genetics on telomere length in mice. Mamm. Genome.
2002;13(5):234-238. DOI 10.1007/s003350020027
Martens D.S., Plusquin M., Cox B., Nawrot T.S. Early biological ag-
ing and fetal exposure to high and low ambient temperature: A birth
cohort study. Environ. Health Perspect. 2019;127(11):117001. DOI
10.1289/EHP5153
McLennan D., Armstrong J.D., Stewart D.C., Mckelvey S., Boner W.,
Monaghan P., Metcalfe N.B. Telomere elongation during early de-
velopment is independent of environmental temperatures in Atlantic
salmon. J. Exp. Biol. 2018;221(Pt. 11):jeb178616. DOI 10.1242/
jeb.178616
Meesters M., Van Eetvelde M., Martens D.S., Nawrot T.S., Dewulf M.,
Govaere J., Opsomer G. Prenatal environment impacts telomere
length in newborn dairy heifers. Sci. Rep. 2023;13(1):4672. DOI
10.1038/s41598-023-31943-8
Miyashita N., Shiga K., Yonai M., Kaneyama K., Kobayashi S., Koji-
ma T., Goto Y., Kishi M., Aso H., Suzuki T., Sakaguchi M., Nagai T.
Remarkable dierences in telomere lengths among cloned cattle de-
rived from dierent cell types. Biol. Reprod. 2002;66(6):1649-1655.
DOI 10.1095/biolreprod66.6.1649
Mizutani Y., Niizuma Y., Yoda K. How do growth and sibling competi-
tion aect telomere dynamics in the rst month of life of long-lived
seabird? PLoS One. 2016;11(11):e0167261. DOI 10.1371/journal.
pone.0167261
Monaghan P., Ozanne S.E. Somatic growth and telomere dynamics in
vertebrates: relationships, mechanisms and consequences. Philos.
Trans. R. Soc. London Ser. B. Biol. Sci. 2018;373(1741):20160446.
DOI 10.1098/rstb.2016.0446
Nowack J., Tarmann I., Hoelzl F., Smith S., Giroud S., Ruf T. Al-
ways a price to pay: hibernation at low temperatures comes with a
trade-o between energy savings and telomere damage. Biol. Lett.
2019;15(10):20190466. DOI 10.1098/rsbl.2019.0466
O’Daniel S.E., Kochan K.J., Long C.R., Riley D.G., Randel R.D.,
Welsh T.H.J. Comparison of telomere length in age-matched pri-
miparous and multiparous Brahman cows. Animals (Basel). 2023;
13(14):2325. DOI 10.3390/ani13142325
Pinese M., Lacaze P., Rath E.M., Stone A., Brion M.-J., Ameur A.,
Nagpal S., … Kaplan W., Gibson G., Gyllensten U., Cairns M.J.,
McNamara M., Dinger M.E., Thomas D.M. The Medical Genome
Reference Bank contains whole genome and phenotype data of
2570 healthy elderly. Nat. Commun. 2020;11(1):435. DOI 10.1038/
s41467-019-14079-0
Purcell S., Neale B., Todd-Brown K., Thomas L., Ferreira M.A.R.,
Bender D., Maller J., Sklar P., de Bakker P.I.W., Daly M.J., Sham P.C.
PLINK: a tool set for whole-genome association and population-
based linkage analyses. Am. J. Hum. Genet. 2007;81(3):559-575.
DOI 10.1086/519795
Rae N., Golpour Hamedani S., Barak F., Safavi S.M., Miraghajani M.
Dietary patterns, food groups and telomere length: a systematic re-
view of current studies. Eur. J. Clin. Nutr. 2017;71(2):151-158. DOI
10.1038/ejcn.2016.149
Raj A., Stephens M., Pritchard J.K. fastSTRUCTURE: variational
inference of population structure in large SNP data sets. Genetics.
2014;197(2):573-589. DOI 10.1534/genetics.114.164350
Влияние породы и среды на длину теломер лейкоцитов
у крупного рогатого скота
Н.С. Юдин, А.В. Игошин, Г.А. Ромашов
А.А. Мартынов, Д.М. Ларкин
2024
28 • 2
197
ГЕНЕТИКА ЖИВОТНЫХ / ANIMAL GENETICS
Funding. The work was supported by the Russian Scientific Foundation grant No. 22-26-00143 (https://rscf.ru/project/22-26-00143/).
Conflict of interest. The authors declare no conflict of interest.
Received December 3, 2023. Revised December 25, 2023. Accepted December 25, 2023.
Reichert S., Stier A., Zahn S., Arrivé M., Bize P., Massemin S., Cris-
cuolo F. Increased brood size leads to persistent eroded telomeres.
Front. Ecol. Evol. 2014;2:9. DOI 10.3389/fevo.2014.00009
Ribas-Maynou J., Llavanera M., Mateo-Otero Y., Ruiz N., Muiño R.,
Bonet S., Yeste M. Telomere length in bovine sperm is related to
the production of reactive oxygen species, but not to reproductive
performance. Theriogenology. 2022;189:290-300. DOI 10.1016/
j.theriogenology.2022.06.025
Rossiello F., Jurk D., Passos J.F., d’Adda di Fagagna F. Telomere dys-
function in ageing and age-related diseases. Nat. Cell Biol. 2022;
24(2):135-147. DOI 10.1038/s41556-022-00842-x
Schrumpfová P.P., Fajkus J. Composition and function of telomerase-A
polymerase associated with the origin of eukaryotes. Biomolecules.
2020;10(10):1425. DOI 10.3390/biom10101425
Seeker L.A., Ilska J.J., Psidi A., Wilbourn R.V., Underwood S.L.,
Fairlie J., Holland R., Froy H., Salvo-Chirnside E., Bagnall A.,
Whitelaw B., Coey M.P., Nussey D.H., Banos G. Bovine telomere
dynamics and the association between telomere length and produc-
tive lifespan. Sci. Rep. 2018a;8(1):12748. DOI 10.1038/s41598-018-
31185-z
Seeker L.A., Ilska J.J., Psidi A., Wilbourn R.V., Underwood S.L.,
Fairlie J., Holland R., Froy H., Bagnall A., Whitelaw B., Coey M.,
Nussey D.H., Banos G. Longitudinal changes in telomere length
and associated genetic parameters in dairy cattle analysed using
random regression models. PLoS One. 2018b;13(2):e0192864. DOI
10.1371/journal.pone.0192864
Seeker L.A., Underwood S.L., Wilbourn R.V., Dorrens J., Froy H., Hol-
land R., Ilska J.J., Psidi A., Bagnall A., Whitelaw B., Coey M.,
Banos G., Nussey D.H. Telomere attrition rates are associated with
weather conditions and predict productive lifespan in dairy cattle.
Sci. Rep. 2021;11(1):5589. DOI 10.1038/s41598-021-84984-2
Sleptsov I.I., Machakhtyrova V.A., Ivanova N.P. Clinical and physio-
logical indicators of the Kalmyk cattle breed in Yakutia conditions.
Bull. Kurgan State Agric. Acad. 2019;4(32):44-46 (in Russian)
Szczotka M., Kocki J., Iwan E., Pluta A. Determination of telomere
length and telomerase activity in cattle infected with bovine leu-
kaemia virus (BLV). Pol. J. Vet. Sci. 2019;22(2):391-403. DOI
10.24425/pjvs.2019.129299
Taub M.A., Conomos M.P., Keener R., Iyer K.R., Weinstock J.S.,
Yanek L.R., Lane J., … de Andrade M., Correa A., Chen Y.I., Boer-
winkle E., Barnes K.C., Ashley-Koch A.E., Arnett D.K.; NHLBI
Trans-Omics for Precision Medicine (TOPMed) Consortium;
TOPMed Hematology and Hemostasis Working Group; TOPMed
Structural Variation Working Group; Laurie C.C., Abecasis G.,
Nickerson D.A., Wilson J.G., Rich S.S., Levy D., Ruczinski I.,
Aviv A., Blackwell T.W., Thornton T., O’Connell J., Cox N.J.,
Perry J.A., Armanios M., Battle A., Pankratz N., Reiner A.P., Ma-
thias R.A. Genetic determinants of telomere length from 109,122 an-
cestrally diverse whole-genome sequences in TOPMed. Cell Genom.
2022;2(1):100084. DOI 10.1016/j.xgen.2021.100084
Tilesi F., Di Domenico E.G., Pariset L., Bosco L., Willems D., Valen-
tini A., Ascenzioni F. Telomere length diversity in cattle breeds. Di-
versity. 2010;2(9):1118-1129. DOI 10.3390/d2091118
Waalen J., Buxbaum J.N. Is older colder or colder older? The associa-
tion of age with body temperature in 18,630 individuals. J. Geron-
tol. A Biol. Sci. Med. Sci. 2011;66(5):487-492. DOI 10.1093/gerona/
glr001
Whittemore K., Vera E., Martínez-Nevado E., Sanpera C., Blasco M.A.
Telomere shortening rate predicts species life span. Proc. Natl.
Acad. Sci. USA. 2019;116(30):15122-15127. DOI 10.1073/pnas.
1902452116
Wilbourn R.V., Moatt J.P., Froy H., Walling C.A., Nussey D.H.,
Boonekamp J.J. The relationship between telomere length and mor-
tality risk in non-model vertebrate systems: a meta-analysis. Philos.
Trans. R. Soc. London Ser. B. Biol. Sci. 2018;373(1741):20160447.
DOI 10.1098/rstb.2016.0447
Zepner L., Karrasch P., Wiemann F., Bernard L. ClimateCharts.net – an
interactive climate analysis web platform. Int. J. Digit. Earth. 2021;
14(3):338-356. DOI 10.1080/17538947.2020.1829112
Zhang D., Newton C.A., Wang B., Povysil G., Noth I., Martinez F.J.,
Raghu G., Goldstein D., Garcia C.K. Utility of whole genome se-
quencing in assessing risk and clinically relevant outcomes for pul-
monary brosis. Eur. Respir. J. 2022;60(6):2200577. DOI 10.1183/
13993003.00577-2022
Zhang H., Liu A., Wang Y., Luo H., Yan X., Guo X., Li X., Liu L.,
Su G. Genetic parameters and genome-wide association studies of
eight longevity traits representing either full or partial lifespan in
Chinese Holsteins. Front. Genet. 2021;12:634986. DOI 10.3389/
fgene.2021.634986
Zhang X., Lin S., Funk W.E., Hou L. Environmental and occupa-
tional exposure to chemicals and telomere length in human stu-
dies. Occup. Environ. Med. 2013;70(10):743-749. DOI 10.1136/
oemed-2012-101350
Zhang Y., Wu Y., Mao P., Li F., Han X., Zhang Y., Jiang S., Chen Y.,
Huang J., Liu D., Zhao Y., Ma W., Songyang Z. Cold-inducible RNA-
binding protein CIRP/hnRNP A18 regulates telomerase activity in
a temperature-dependent manner. Nucleic Acids Res. 2016;44(2):
761-775. DOI 10.1093/nar/gkv1465
Zhao Z., Cao J., Niu C., Bao M., Xu J., Huo D., Liao S., Liu W., Speak-
man J.R. Body temperature is a more important modulator of life-
span than metabolic rate in two small mammals. Nat. Metab. 2022;
4(3):320-326. DOI 10.1038/s42255-022-00545-5
