The synergism of age and db/db genotype impairs wound healing

Harold Brem, Marjana Tomic-Canic, Hyacinth Entero, Andrew M. Hanflik, Vincent M. Wang, John T. Fallon, H. Paul Ehrlich

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Both diabetes and advanced age have been implicated in delaying wound repair. However, the contribution of age alone has not been shown clinically to significantly impair the ability to heal. To determine the contribution of age and db/db genotype multiple wound healing parameters were determined in young db/db mice, aged db/db mice, age-matched non-db/db control and wild-type C57BL/6 mice. Biomechanical properties (breaking load and tensile stiffness), epithelialization, and collagen deposition were determined for the four groups of mice 14 days after wounding with suture-closed incisional wounds. While neither hyperglycemia nor age alone caused impairment in biomechanical properties, the combination of age and db/db genotype resulted in a 36% reduction in stiffness and a 42% reduction in breaking load, when compared to young control mice, suggesting poor quality of healing. Statistically significant differences in the volume of granulation tissue deposited within the wound site were also observed, with the aged db/db mice displaying more than any other group, suggesting greater dermal loss from the dermal edges of incisional wounds in aged db/db mice, suggesting that the combination of age and diabetes act synergistically to impair healing in mice with type 2 diabetes. Interestingly, the impairment occurs independently of the prevailing glycemia, supporting the hypothesis that diabetes in synergy with advanced age has downstream effects, leading to further impairment, necessitating initiation of early and aggressive intervention in elderly patients with diabetic foot ulcers.

Original languageEnglish
Pages (from-to)523-531
Number of pages9
JournalExperimental Gerontology
Volume42
Issue number6
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

Fingerprint

Medical problems
Wound Healing
Genotype
Loads (forces)
Stiffness
Wounds and Injuries
Granulation
Repair
Collagen
Skin
Tissue
Diabetic Foot
Granulation Tissue
Inbred C57BL Mouse
Hyperglycemia
Type 2 Diabetes Mellitus
Sutures

Keywords

  • db/db mouse model
  • Diabetes
  • Effects of aging
  • Pathology
  • Wound healing

ASJC Scopus subject areas

  • Aging
  • Medicine(all)

Cite this

Brem, H., Tomic-Canic, M., Entero, H., Hanflik, A. M., Wang, V. M., Fallon, J. T., & Ehrlich, H. P. (2007). The synergism of age and db/db genotype impairs wound healing. Experimental Gerontology, 42(6), 523-531. https://doi.org/10.1016/j.exger.2006.11.018

The synergism of age and db/db genotype impairs wound healing. / Brem, Harold; Tomic-Canic, Marjana; Entero, Hyacinth; Hanflik, Andrew M.; Wang, Vincent M.; Fallon, John T.; Ehrlich, H. Paul.

In: Experimental Gerontology, Vol. 42, No. 6, 01.06.2007, p. 523-531.

Research output: Contribution to journalArticle

Brem, H, Tomic-Canic, M, Entero, H, Hanflik, AM, Wang, VM, Fallon, JT & Ehrlich, HP 2007, 'The synergism of age and db/db genotype impairs wound healing', Experimental Gerontology, vol. 42, no. 6, pp. 523-531. https://doi.org/10.1016/j.exger.2006.11.018
Brem, Harold ; Tomic-Canic, Marjana ; Entero, Hyacinth ; Hanflik, Andrew M. ; Wang, Vincent M. ; Fallon, John T. ; Ehrlich, H. Paul. / The synergism of age and db/db genotype impairs wound healing. In: Experimental Gerontology. 2007 ; Vol. 42, No. 6. pp. 523-531.
@article{f2cf124f3952438693f10f132ea17394,
title = "The synergism of age and db/db genotype impairs wound healing",
abstract = "Both diabetes and advanced age have been implicated in delaying wound repair. However, the contribution of age alone has not been shown clinically to significantly impair the ability to heal. To determine the contribution of age and db/db genotype multiple wound healing parameters were determined in young db/db mice, aged db/db mice, age-matched non-db/db control and wild-type C57BL/6 mice. Biomechanical properties (breaking load and tensile stiffness), epithelialization, and collagen deposition were determined for the four groups of mice 14 days after wounding with suture-closed incisional wounds. While neither hyperglycemia nor age alone caused impairment in biomechanical properties, the combination of age and db/db genotype resulted in a 36{\%} reduction in stiffness and a 42{\%} reduction in breaking load, when compared to young control mice, suggesting poor quality of healing. Statistically significant differences in the volume of granulation tissue deposited within the wound site were also observed, with the aged db/db mice displaying more than any other group, suggesting greater dermal loss from the dermal edges of incisional wounds in aged db/db mice, suggesting that the combination of age and diabetes act synergistically to impair healing in mice with type 2 diabetes. Interestingly, the impairment occurs independently of the prevailing glycemia, supporting the hypothesis that diabetes in synergy with advanced age has downstream effects, leading to further impairment, necessitating initiation of early and aggressive intervention in elderly patients with diabetic foot ulcers.",
keywords = "db/db mouse model, Diabetes, Effects of aging, Pathology, Wound healing",
author = "Harold Brem and Marjana Tomic-Canic and Hyacinth Entero and Hanflik, {Andrew M.} and Wang, {Vincent M.} and Fallon, {John T.} and Ehrlich, {H. Paul}",
year = "2007",
month = "6",
day = "1",
doi = "10.1016/j.exger.2006.11.018",
language = "English",
volume = "42",
pages = "523--531",
journal = "Experimental Gerontology",
issn = "0531-5565",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - The synergism of age and db/db genotype impairs wound healing

AU - Brem, Harold

AU - Tomic-Canic, Marjana

AU - Entero, Hyacinth

AU - Hanflik, Andrew M.

AU - Wang, Vincent M.

AU - Fallon, John T.

AU - Ehrlich, H. Paul

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Both diabetes and advanced age have been implicated in delaying wound repair. However, the contribution of age alone has not been shown clinically to significantly impair the ability to heal. To determine the contribution of age and db/db genotype multiple wound healing parameters were determined in young db/db mice, aged db/db mice, age-matched non-db/db control and wild-type C57BL/6 mice. Biomechanical properties (breaking load and tensile stiffness), epithelialization, and collagen deposition were determined for the four groups of mice 14 days after wounding with suture-closed incisional wounds. While neither hyperglycemia nor age alone caused impairment in biomechanical properties, the combination of age and db/db genotype resulted in a 36% reduction in stiffness and a 42% reduction in breaking load, when compared to young control mice, suggesting poor quality of healing. Statistically significant differences in the volume of granulation tissue deposited within the wound site were also observed, with the aged db/db mice displaying more than any other group, suggesting greater dermal loss from the dermal edges of incisional wounds in aged db/db mice, suggesting that the combination of age and diabetes act synergistically to impair healing in mice with type 2 diabetes. Interestingly, the impairment occurs independently of the prevailing glycemia, supporting the hypothesis that diabetes in synergy with advanced age has downstream effects, leading to further impairment, necessitating initiation of early and aggressive intervention in elderly patients with diabetic foot ulcers.

AB - Both diabetes and advanced age have been implicated in delaying wound repair. However, the contribution of age alone has not been shown clinically to significantly impair the ability to heal. To determine the contribution of age and db/db genotype multiple wound healing parameters were determined in young db/db mice, aged db/db mice, age-matched non-db/db control and wild-type C57BL/6 mice. Biomechanical properties (breaking load and tensile stiffness), epithelialization, and collagen deposition were determined for the four groups of mice 14 days after wounding with suture-closed incisional wounds. While neither hyperglycemia nor age alone caused impairment in biomechanical properties, the combination of age and db/db genotype resulted in a 36% reduction in stiffness and a 42% reduction in breaking load, when compared to young control mice, suggesting poor quality of healing. Statistically significant differences in the volume of granulation tissue deposited within the wound site were also observed, with the aged db/db mice displaying more than any other group, suggesting greater dermal loss from the dermal edges of incisional wounds in aged db/db mice, suggesting that the combination of age and diabetes act synergistically to impair healing in mice with type 2 diabetes. Interestingly, the impairment occurs independently of the prevailing glycemia, supporting the hypothesis that diabetes in synergy with advanced age has downstream effects, leading to further impairment, necessitating initiation of early and aggressive intervention in elderly patients with diabetic foot ulcers.

KW - db/db mouse model

KW - Diabetes

KW - Effects of aging

KW - Pathology

KW - Wound healing

UR - http://www.scopus.com/inward/record.url?scp=34248529660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34248529660&partnerID=8YFLogxK

U2 - 10.1016/j.exger.2006.11.018

DO - 10.1016/j.exger.2006.11.018

M3 - Article

C2 - 17275236

AN - SCOPUS:34248529660

VL - 42

SP - 523

EP - 531

JO - Experimental Gerontology

JF - Experimental Gerontology

SN - 0531-5565

IS - 6

ER -