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Telomere length: any perspective as a biomarker for longevity in dairy cows? Susanne Häußler & Lilian Laubenthal University of Bonn Institute of Animal Sciences, Physiology & Hygiene Unit 1 st Dairy Care Conference, Copenhagen, August 23 rd 2014

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Page 1: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

Telomere length:

any perspective as a biomarker for

longevity in dairy cows?

Susanne Häußler & Lilian Laubenthal

University of Bonn Institute of Animal Sciences, Physiology & Hygiene Unit

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 2: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

Telomeres

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m/2

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-with-d

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]

• protect chromosomal integrity

• allow for complete replication of genomic DNA (BROWN ET AL. 2012)

2 1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 3: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

SHAMMAS 2011

Telomeres

• [TTAGGG]n repeats on the end of chromosomes

• 5 – 15 kilobase pairs of telomere repeats

3

sub-telomeric DNA TTAGGG repeats

interact with specific

proteins

looped confirmation (AUBERT & LANSDORP 2008)

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 4: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

Telomeres

4

young

cells

old

cells

1st Dairy Care Conference, Copenhagen, August 23rd 2014

(AUBERT & LANSDORP 2008)

Page 5: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

Telomerase

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/ww

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ss 1

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]

• reverse transcriptase

• add nucleotides for telomeric DNA

• replenish telomeres (AUTEXIER & LUE 2006)

5 1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 6: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

6

Telomere length

shortening lengthening

cell

proliferation cellular

stress telomerase

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 7: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

7

Causes of telomere shortening

Telomere

shortening

oxidative

stress

chronic

stress

inflammation

immune

exhaustion

(EITAN ET AL. 2014)

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Telomere shortening is associated with ageing and

age-related pathologies in humans (BLASCO 2007)

Page 8: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

increased susceptibility to metabolic disorders

compromised immune response (MALLARD ET AL. 1998) and

reduced fertility (BUTLER & SMITH 1989)

High-yielding dairy cows

milk

synthesis

lipolysis dry matter

intake

nutrient

demand

8

Early lactation

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 9: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

over-conditioned versus lean cows:

• greater incidence of health problems in the transition period

High-yielding dairy cows

9

mid to late lactation

body

weigth

lipogenesis dry matter

intake

milk

synthesis

(reviewed by SORDILLO & RAPHAEL 2013)

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 10: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

10

Telomere length in dairy cows

oxidative

stress

chronic

stress

inflammation

immune

exhaustion

Telomere

shortening

• reduced telomere length in cattle related to age and herd

environment (BROWN ET AL. 2012)

chronic stress response

1st Dairy Care Conference, Copenhagen, August 23rd 2014

• telomeres respond to environmental changes and stressors (THEALL ET AL. 2013)

Page 11: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

11 1st Dairy Care Conference, Copenhagen, August 23rd 2014

Hypothesis

Telomeres shorten in bovine adipose tissue

in association with

increased oxidative stress.

Page 12: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

Thank you!

e-mail: [email protected]

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 13: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

13

Experimental design

540 ± 20 Body weight (kg) 792 ± 29

2.31 ± 0.12 Body condition score 4.53 ± 0.14

1st Dairy Care Conference, Copenhagen, August 23rd 2014

AT biopsy

+ blood

AT biopsy

+ blood Sampling:

Page 14: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

14 1st Dairy Care Conference, Copenhagen, August 23rd 2014

Methods

Data analysis:

Mann-Whitney-Test and Spearman correlation (SPSS 22)

Telomere quantitiy Derivates of reactive

oxygen metabolites

(dROM)

Page 15: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

weeks of conditioning

telo

mere

pro

du

cts

/b-g

lob

in

P = 0.01

Telomere quantity

Telomeres in bovine adipose tissue

15

Correlation between

quantitiy of telomeres and dROM

r = -0.596; P = 0.015

LAUBENTHAL ET AL. 2014

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Page 16: Telomere length: any perspective as a biomarker for ... · 540 ± 20 Body ... AT biopsy + blood Sampling: 14 1st Dairy Care Conference, Copenhagen, August 23rd 2014 Methods Data analysis:

16

Perspective

Saliva

• non-invasive

• ideal medium to monitor long-term effects of metabolic

stress in dairy cows

Catch-AllTM buccal swab

1st Dairy Care Conference, Copenhagen, August 23rd 2014

Telomeres:

• mirror chronic stress, environmental influences and

health disorders

• biomarker for longevity in dairy cows