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Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology of Aging and Evaluating Effects of Calorie Restriction

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Page 1: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Mary Ann OttingerIPA, LEG/NIA

Department of Animal and Avian Sciences, University of Maryland,

College Park, MD

Avian Models for the Comparative Biology of Aging and Evaluating Effects

of Calorie Restriction

Page 2: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Why is an avian system of interest and is there relevance for other species/phyla?

Understand basic biological processes, especially aging

Calorie restriction and has been used to optimize health and reproduction in domestic species for many years.

Domestic poultry include genetic strains selected for growth, disease resistance, reproductive and metabolic endocrine characteristics.

Some birds age rapidly (Japanese quail and domestic poultry); others have long lifespans and do not show classic signs of aging (terns and other sea birds, cranes, kestrals, humming birds).

Page 3: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Do Avian Species Have Similar Lifetime Reproductive Patterns?

Within classes patterns of aging appear similar

Some species with a relatively long life-span show little sign of aging

Page 4: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

CHOOSING APPROPRIATE MEASURES

LIFESPAN• What are the constraints?REPRODUCTION• Fertility• Number of viable young• Years of productivity• Reproductive success of offspringMETABOLIC ENDOCRINE • IGF-1, thyroid hormone, GHAGING• Post reproductive lifespan?• Biomarkers of aging (skin, etc)• ?

Page 5: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

What Needs to be Considered?

COMPARISON WITHIN A SPECIES • Individual variability • Environmental factors

(nutrition, stress, housing, photoperiod)• Captive versus wild

(seasonal factors, disease, predation, etc)

COMPARISONS BETWEEN SPECIES• Lifetime strategies in reproduction

(# young/year, precocial vs altricial)• Environmental factors

(season, migratory, nutrition, etc)

Page 6: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

COMPARING JAPANESE QUAIL AND KESTRELS (Work in Collaboration with Dr.

John French, USGS-Patuxent Wildlife Research CenterJAPANESE QUAIL•Short lived; terrestrial; migratory; omnivore •Rapidly aging•Large clutches; precocial chicks; coveys•Sex difference in senescence•Reproductive, metabolic, and sensory systems aging all decline •Neuroplasticity

KESTRELS•Long lived; terrestrial; carnivore•Slow maturation and aging•Small clutches; altricial; small groups•Pair bond

Page 7: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Relative Patterns in Reproduction

0255075

100%

repr

oduc

tive quail

terns

cranes

Page 8: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Relative Patterns in Reproduction

0

25

50

75

100

% re

prod

ucti

vequail

terns

cranes

kestrels

Species Lifespan (yrs) Clutch sizeQuail 2-5 yrs 12-15Terns 20-30 yrs 2.2Kestrel 12-15 yrs 4.5 Crane 35-40 yrs 1.4

Page 9: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Relative Patterns in Reproduction

0255075

100

mat

urat

ion ad

ult

(pea

k)

earl

yag

ing

sene

scen

t

% re

prod

ucti

ve J apanesequail

bobwhitequail

Page 10: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

American Kestrel colony at the Patuxent Wildlife Research

Center

Page 11: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

ID Male Female Inbreeding Coefficient Pen Hatch year M/F Endpoint

1 K0403 K0467 0.0222 665 91/91

2 K0319 K0412 0.0169 659 91/91 *stopped laying 2002

3 K0373 K0404 0.0062 658 91/91 *

4 K0413 K0389 0.0116 653 91/91

5 K0445 K0387 0.0134 652 91/91 *

6 K0312 K0385 0.0283 651 91/91

7 K0375 K0369 0.0149 650 91/91 *

8 K0336 K0367 0.0118 649 91/91 Female died 1997

9 K0341 K0357 0.0146 647 91/91 *

10 K0406 K0444 0.0034 644 91/91 *

11 K0410 K0303 0.0161 642 91/91

12 K0464 K0398 0.0128 641 91/91

13 K0407 K0338 0.0193 640 91/91 Female died 1997

14 K0408 K0328 0.0121 635 91/91

15 K0221 K0261 0.0039 679 90/90 *stopped laying 2002

16 K0231 K0246 0.0124 677 90/90

17 K0251 K0300 0.0234 675 90/90

18 K0287 K0361 0.0152 673 90/91

19 K0470 K0322 0.0135 670 91/91

20 K0450 K0443 0.0144 669 91/91

Using Microsoft Access to Follow Individuals and Pairs

Page 12: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Year

Male Age

Female Age

Start Date - Days off Mean

# Eggs Layed

# Fertile

# Hatched

# Fledged

Comments

1993

2 2 0 5 5 5 5

1994

3 3 1 5 5 5 5

1995

4 4 0 4 4 3 3 1 egg died

1996

5 5 1 4 - - - eggs euthanized

1997

6 6 0 5 5 3 3 2 eggs euthanized

1998

7 7 0 5 3+ 2 1 2 eggs lost; 1 hatchling died before fledge

1999

8 8 0 5 4 - - eggs euthanized

2000

9 9 0 5 3+ 0 0 1 egg lost; 3 eggs dead; 1 egg infertile

2001

10 10 1 5 2+ 2 1 2 eggs lost; I egg infertile; 1 hatchling died

2002

11 11 none 0 0 0 0 never laid

Page 13: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Current data for American kestrels

Cross sectional: Blood chemistry, cell counts [..years?] WNV antibody titer

Longitudinal Body weight Reproduction: date 1st egg, clutch size, fertility,

egg weight, proportions hatch & ‘fledge’

Page 14: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Age (x) nSurvival

Rate (sx)Survival

(lx)Life Expectancy

(ex)

0 884 0.893 1.000 4.784

1 85 1.000 0.893 3.784

2 84 0.881 0.893 2.784

3 69 0.942 0.787 2.815

4 59 0.932 0.741 2.304

5 45 0.867 0.691 1.790

6 34 0.882 0.599 1.615

7 22 0.955 0.528 1.333

8 20 0.750 0.504 0.500

9 14 0.867 0.378 0.333

10 13 0.923 0.328 0.167

11 12 1.000 0.339 1.000

12 2 ? ? ?

AMERICAN KESTREL Life Table

PATUXENT WILDLIFE RESEARCH CENTER

1993 - 2000

Note:

- estimate of S0 from fledging

- missing 1y information

- includes all birds (partial LH)

- birds from 1991 on: earlier?

- all 11, 12y birds still alive

- evidence of aging?

Page 15: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Studies in Broiler Breeders

hatch maturation adult (peak reprod, health, metabolism) aging Age 0-3 or…8wks 18-24 wks 28-55 wks 56-64 wks

diet ad lib skip a day restricted daily feeding

DietGroup 1: ad lib weeks 1-3; 15% CR

Group 2: ad lib weeks 1-8; 15% CR

Page 16: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Females initiating CR at 3 weeks matured slower; egg production continued at a higher level than birds full fed for 8 weeks and then restricted.

0

50

100

28 36 44 52 60

weeks of age

eg

g p

rod

uc

tio

n

(% h

en

da

y)

3 wk-15%CR

8 wk-15%CR

Page 17: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

(Robinson et al., 20002)

As the hen ages, the number of eggs laid in a sequence declines, due to increasing irregular ovulation.

CR AL

LCR hens lay regularly as they age, with less signs of aging.

Eggs are produced in a hierarchy with daily ovoposition; yolk accumulation occurs over several days.

Page 18: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Studies in Broiler Breeders

hatch maturation adult (peak reprod, health, metabolism) aging Age 0-3 wks 18-24 wks 28-55 wks 56-64 wks

Diet: ad lib skip a day restricted daily feeding

DietGroup 1: ad lib weeks 1-3; then 15% CR

Group 2: ad lib weeks 1-3; 15% CR until mature (24 wks); then 37% CR

Group 3: low protein diet weeks 1-10; then 15% CR

Page 19: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

0

20

40

60

80

100

eg

g p

rod

uc

tio

n

35 39 52 61

weeks in age

Egg Production (% hen day)

15% CR

15-35% CR

15% CR (lowprotein)

Fertility

0

20

40

60

80

100

32 42 52 61weeks in age

% fe

rtili

ty

Hatching success

010

203040

506070

8090

32 42 52 61weeks in age

%ha

tch

Page 20: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

The Japanese Quail as a Model System for Studying AgingNatural historyCharacteristics of aging in male quail

sexual behavior as an index of reproductive status

circulating hormone levels phases in reproductive aging

Page 21: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

The Hypothalamic-Pituitary-Gonadal Axis in Japanese Quail

Hypothalamus GnRH-I

Pituitary Gland LH, FSH

Gonadsandrogens, estrogens, progestins

+

+

NEDA

Opioid peptides

OTAVTGABA- + -

Neuroendocrine systems regulate endocrine and behavioral components of reproduction.

Page 22: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Table 1: Effects of CR in adult male Japanese quail after 8 weeks treatment

(different letters denote significant (p<0.05) differences within a column).

% CR Body weight

gm

Testes

weight

LH ng/ml

plasma

Androgen

pg/ml

Corticos

ng/ml

0% 115a 3.1

a 7.2

a 2828

a 3.1

a

20% 97b 3.3

a 4.7

b 1392

b 2.8

a

40% 75c 2.2

b 2.5

c 266

c 7.2

b

Page 23: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Effects of Calorie Restriction in Japanese Quail (% difference between 20 or 40% CR with pair fed ad

lib control; data expressed as % difference)

0

25

50

75

100

125

150

% o

f Con

trol

body wt testes wt LH androgen cort

control

20% CR

40% CR

(230%)

from Mobarak, Abdelnabi, and Ottinger, 1995

Page 24: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

Saline treatment

Saline treatment

LHRH challenge

LHRH challenge

Treatment Preinjection Post inj (15 min)

Preinjection Post inj (15 min)

0% CR 6.5a 5.6a 6.8a 9.8b

20% CR 4.8c 4.0c 4.6c 9.4b

40% CR 2.4d 1.9d 1.8d 6.8a

Effects of LHRH challenge (20 g/kg body weight) in castrated CR males on serum LH (ng/ml plasma; different

letters denote significant (p<0.05) differences in rows).

Page 25: Mary Ann Ottinger IPA, LEG/NIA Department of Animal and Avian Sciences, University of Maryland, College Park, MD Avian Models for the Comparative Biology

AcknowledgementsThis work has been supported by the Maryland Agriculture Experiment Station, University of Maryland, College Park, NRI #92-37203 and NSF #9817024 (MAO).

Dr. Joseph SoaresDr. Mohammed MobarakDr. Estelle Russek-CohenDr. Mahmoud AbdelnabiNichola ThompsonDr. Robert ClarkeDr. Qichang LiOur animal care crew!