AGE

, Volume 33, Issue 3, pp 461–473 | Cite as

Age relationships of postmortem observations in Portuguese Water Dogs

  • Kevin Chase
  • Dennis F. Lawler
  • Lawrence D. McGill
  • Shawn Miller
  • Mark Nielsen
  • Karl G. Lark
Article

Abstract

A dog model has been used to evaluate histological changes arising from senescence. Autopsies of 145 Portuguese Water Dogs have been used to evaluate the individual and group “state of health” at time of death. For each dog, weights or dimensions of organs or tissues were obtained, together with histological evaluation of tissues. Twenty-three morphological metrics correlated significantly to age at death. Many of these involved muscles; others were associated with derivatives of embryonic foregut. The latter included lengths of the small intestine and trachea as well as weights of the stomach and some lung lobes. Nearly all of the dogs examined had histological changes in multiple tissues, ranging from two to 12 per dog. Associations among pathologies included inflammatory bowel disease with osteoporosis and dental calculus/periodontitis with atherosclerosis and amyloidosis. In addition, two clusters of histological changes were correlated to aging: hyperplasia, frequency of adenomas, and hemosiderosis constituted one group; inflammation, plasmacytic and lymphocytic infiltration, fibrosis, and atrophy, another. Heritability analysis indicated that many of the changes in tissue/organ morphology or histology could be heritable and possibly associated with IGF1, but more autopsies will be required to substantiate these genetic relationships.

Keywords

Age of death Autopsy Dog Pathology Histology 

Notes

Acknowledgements

This research was supported by a grant to KGL from NIH (GM063056) as well as gifts from the Judith L. Chiara Fund, from the Purina Nestle Co. and smaller gifts from a large number of Portuguese Water Dog owners. We would like to thank the following undergraduate students for invaluable assistance carrying out gross autopsies: Nicholas S. Livdahl, Armando M. Calderon, Chandra Hayes, Richard W. Homer, Nathan T. Mortensen, Spencer B. Dowdle, Heather Hawker, and Mark S. Vantassell. Deborah Broughton arranged with individual owners for the transfer of deceased dogs to the University of Utah. Without her sensitive and caring assistance, this project would not have been possible. Karen Miller, director of “The Georgie Project” played a crucial role in the initial stages of this project informing PWD owners and breeders of the importance of autopsy as a key to improving the health of their breed.

Finally, we cannot begin to express our endebtedness to the very many Portuguese Water Dog owners and breeders, whose love for their breed led them to participate in the autopsy project. Their care and tender thoughtfulness at a time when parting was most painful and participation was a final act of saying goodbye stands as a monument to what people can do when they really care about others.

Supplementary material

11357_2010_9181_MOESM1_ESM.doc (105 kb)
Supplementary Table 1Portuguese Water Dog autopsy protocol (DOC 105 kb)
11357_2010_9181_MOESM2_ESM.doc (103 kb)
Supplementary Table 2Most frequent non-neoplastic histological changes (DOC 103 kb)

References

  1. Amenta PS, Martinez-Hernandez A, Trelstad RL (1990) Repair and regeneration. In: Damjanov I, Linder J (eds) Anderson’s pathology, 10th edn. Mosby, St. Louis, pp 416–447Google Scholar
  2. Arden NK, Cooper C (2002) Osteoporosis in patients with inflammatory bowel disease. Gut 50(1):9–10PubMedCrossRefGoogle Scholar
  3. Aupperle H, Marz I, Ellenberger C, Buschatz S, Reischauer A, Schoon HA (2007) Primary and secondary heart tumours in dogs and cats. J Comp Pathol 136:18–26PubMedCrossRefGoogle Scholar
  4. Barthet M, Lesavre N, Desplats S, Panuel M, Gasmi M, Bernard JP, Dagorn JC, Grimaud JC (2006) Frequency and characteristics of pancreatitis in patients with inflammatory bowel disease. Pancreatology 6:464–471PubMedCrossRefGoogle Scholar
  5. Bartke A (2005) Minireview: role of the growth hormone/insulin-like growth factor system in mammalian aging. Endocrinology 146:3718–3723PubMedCrossRefGoogle Scholar
  6. Chase K, Adler FR, Miller-Stebbings K, Lark KG (1999) Teaching a new dog old tricks: identifying quantitative trait loci [in dogs] using lessons from plants. J Heredity 90:43–51CrossRefGoogle Scholar
  7. Chase K, Carrier DR, Adler FR, Jarvik T, Ostrander EA, Lorentzen TD, Lark KG (2002) Genetic basis for systems of skeletal quantitative traits: principal component analysis of the canid skeleton. Proc Natl Acad Sci USA 99:9930–9935PubMedCrossRefGoogle Scholar
  8. Chase K, Sargan D, Miller K, Ostrander EA, Lark KG (2006) Understanding the genetics of autoimmune disease: two loci that regulate late onset Addison’s disease in Portuguese Water Dogs. Int J Immunogenet 33:179–184PubMedCrossRefGoogle Scholar
  9. Chase K, Jones P, Martin A, Ostrander EA, Lark KG (2009) Genetic mapping of fixed phenotypes: disease frequency as a breed characteristic. J Hered 100(Suppl 1):S37–S41PubMedCrossRefGoogle Scholar
  10. Cheville N (1983) Inflammation and repair. In: Cheville N (ed) Cell pathology, 2nd edn. Iowa State University Press, Ames, pp 236–297Google Scholar
  11. Clark RD, Stainer JR (1994) Medical & genetic aspects of purebred dogs. Forum, Fairway, pp 432–436Google Scholar
  12. Clifford D, McCullagh P (2006) The regress library. R News: The Newsletter of the R Project. http://www.r-project.org/doc/Rnews/Rnews_2006-2.pdf. Accessed 01 June 2006
  13. Davis A (2007) Dog days of science. NIH/OER Animals in Research Web SiteGoogle Scholar
  14. de la Grandmaison GL, Clairand I, Durigon M (2001) Organ weight in 684 adult autopsies: new tables for a Caucasoid population. Forensic Sci Int 119:149–154PubMedCrossRefGoogle Scholar
  15. Dungworth RL (1993) The respiratory system. In: Jubb KVF, Kennedy PC, Palmer N (eds) Pathology of domestic animals, vol 2, 4th edn. Academic, San Diego, pp 584–588Google Scholar
  16. Falconer DS, Mackay TFC (1996) Introduction to quantitative genetics. Longman, New YorkGoogle Scholar
  17. Fleischer S, Sharkey M, Mealey K, Ostrander EA, Martinez M (2008) Pharmacogenetic and metabolic differences between dog breeds: their impact on canine medicine and the use of the dog as a preclinical animal model. AAPS J 10:110–119PubMedCrossRefGoogle Scholar
  18. Galis F, Van Der Sluijs I, Van Dooren TJM, Metz JAJ, Nussbaumer M (2007) Do large dogs die young? J Exp Zoolog B Mol Dev Evol 308B:119–126CrossRefGoogle Scholar
  19. Gough A, Thomas A (2004) Breed predispositions to diseases in dogs & cats. Blackwell, Ames, p 124CrossRefGoogle Scholar
  20. Grauer GF, DiBartola SP (2000) Glomerular disease. In: Ettinger SJ, Feldman EC (eds) Textbook of veterinary internal medicine, vol 2, 5th edn. Saunders, Philadelphia, pp 1662–1678Google Scholar
  21. Haddad S, Restieri C, Krishnan K (2001) Characterization of age-related changes in body weight and organ weights from birth to adolescence in humans. J Toxicol Environ Health A 64:453–464PubMedCrossRefGoogle Scholar
  22. Hall EH, Simpson KW (2000) Diseases of the small intestine. In: Ettinger SJ, Feldman EC (eds) Textbook of veterinary internal medicine, 5th edn. Saunders, Philadelphia, pp 1182–1238Google Scholar
  23. Jones P, Chase K, Martin A, Davern P, Ostrander EA, Lark KG (2008) Single-nucleotide-polymorphism-based association mapping of dog stereotypes. Genetics 179:1033–1044PubMedCrossRefGoogle Scholar
  24. Jubb KVF, Kennedy PC, Palmer N (1993) Pathology of domestic animals, vol 2, 4th edn. Academic, San Diego, p 329Google Scholar
  25. Kenyon C (2001) A conserved regulatory system for aging. Cell 105:165–168PubMedCrossRefGoogle Scholar
  26. Lark K, Chase K, Carrier D, Adler F (2006a) Genetic analysis of the canid skeleton: Analysis of morphological loci (QTLs) in the Portuguese water dog population. In: Ostrander EA, Giger U, Lindblad-Toh K (eds) The genome of the domestic dog. Cold Spring Harbor Press, Woodbury, pp 67–80Google Scholar
  27. Lark KG, Chase K, Sutter NB (2006b) Genetic architecture of the dog: sexual size dimorphism and functional morphology. Trends Genet 22:537–544PubMedCrossRefGoogle Scholar
  28. Lawler DF, Chase K, Teckenbrock R, Lark KG (2006) Heritable components of feline hematology, clinical chemistry, and acid-base profiles. J Hered 97:549–554PubMedCrossRefGoogle Scholar
  29. Lawler DF, Larson BT, Ballam JM, Smith GK, Biery DN, Evans RH, Greeley EH, Segre M, Stowe HD, Kealy RD (2008) Diet restriction and ageing in the dog: major observations over two decades. Br J Nutr 99:793–805PubMedCrossRefGoogle Scholar
  30. Lin S-L, Kisseleva T, Brenner DA, Duffield JS (2008) Pericytes and perivascular fibrosis are the primary source of collagen-producing cells in obstructive fibrosis of the kidney. Am J Pathol 173:1617–1726PubMedCrossRefGoogle Scholar
  31. MacEwen EG, Pastor J, Kutzke J, Tsan R, Kurzman ID, Thamm DH, Wilson M, Radinsky R (2004) IGF-1 receptor contributes to the malignant phenotype in human and canine osteosarcoma. J Cell Biochem 92:77–91PubMedCrossRefGoogle Scholar
  32. Manly BFJ (1997) Randomization and Monte Carlo methods in biology. Chapman and Hall, New York, pp 148–169Google Scholar
  33. Maxie MG (1993) The urinary system. In: Jubb KVF, Kennedy PC, Palmer N (eds) Pathology of domestic animals, vol 2, 4th edn. Academic, San Diego, pp 468–470Google Scholar
  34. Molinari C (1993) The Portuguese water dog. ELO-Publicidade, PortugalGoogle Scholar
  35. Pavlica Z, Petelin M, Juntes P, Erzen D, Crossley DA, Skaleric U (2008) Periodontal disease burden and pathological changes in organs of dogs. J Vet Dent 25:97–105PubMedGoogle Scholar
  36. R Development Core Team (2006) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, ViennaGoogle Scholar
  37. Renvert S (2003) Destructive periodontal disease in relation to diabetes mellitus, cardiovascula disease, osteoporosis and respiratory disease. Oral Health Prev Dentist 1(Suppl 1):341–357Google Scholar
  38. Robinson WF, Maxie MG (1993a) The cardiovascular system. In: Jubb KVF, Kennedy PC, Palmer N (eds) Pathology of domestic animals, vol 3, 4th edn. Academic, San Diego, pp 66–67Google Scholar
  39. Robinson WF, Maxie MG (1993b) The heart. In: Jubb KVF, Kennedy PC, Palmer N (eds) Pathology of domestic animals, vol 3, 4th edn. Academic, San Diego, pp 1–47Google Scholar
  40. Rodriguez S, Gaunt TR, Day IN (2007) Molecular genetics of human growth hormone, insulin-like growth factors and their pathways in common disease. Hum Genet 122:1–21PubMedCrossRefGoogle Scholar
  41. Seluanov A, Hine C, Bozzella M, Hall A, Sasahara TH, Ribeiro AA, Catania KC, Presgraves DC, Gorbunova V (2008) Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan. Aging Cell 7:813–823PubMedCrossRefGoogle Scholar
  42. Seyrig J-A, Jian R, Modigliani R, Golfain D, Florent C, Messing B, Bitoun A (1985) Idiopathic pancreatitis associated with inflammatory bowel disease. Dig Dis Sci 30:1121–1126PubMedCrossRefGoogle Scholar
  43. Slavkin HC, Baum BJ (2000) Relationship of dental and oral pathology to systemic illness. J Am Med Assoc 284:1215–1217CrossRefGoogle Scholar
  44. Sutter NB, Ostrander EA (2004) Dog star rising: the canine genetic system. Nat Rev Genet 5:900–910PubMedCrossRefGoogle Scholar
  45. Sutter NB, Bustamante CD, Chase K, Gray MM, Zhao K, Zhu L, Padhukasahasram B, Karlins E, Davis S, Jones PG, Quignon P, Johnson GS, Parker HG, Fretwell N, Mosher DS, Lawler DF, Satyaraj E, Nordborg M, Lark KG, Wayne RK, Ostrander EA (2007) A single IGF1 allele is a major determinant of small size in dogs. Science 316:112–115PubMedCrossRefGoogle Scholar
  46. Triantafillidis JK, Cheracakis P, Merikas EG, Gikas A, Mylonaki M, Georgopoulos F (2004) Acute idiopathic pancreatitis in patients with inflammatory bowel disease: a retrospective case-series description. Annals Gastroenterology 17:288–293Google Scholar
  47. Tromm A, Huppe D, Micklefield GH, Schwegler U, May B (1992) Acute pancreatitis complicating Crohn’s disease: mere coincidence or causality? Gut 33:1289–1291PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2010

Authors and Affiliations

  • Kevin Chase
    • 1
  • Dennis F. Lawler
    • 2
  • Lawrence D. McGill
    • 3
  • Shawn Miller
    • 1
  • Mark Nielsen
    • 1
  • Karl G. Lark
    • 1
  1. 1.Department of BiologyUniversity of UtahSalt Lake CityUSA
  2. 2.O’FallonUSA
  3. 3.Animal Reference Pathology DivisionARUPSalt Lake CityUSA

Personalised recommendations