The synergism of age and db/db genotype impairs wound healing.
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.
Brem
Harold
H
Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, USA. hb2133@columbia.edu <hb2133@columbia.edu>
Tomic-Canic
Marjana
M
Entero
Hyacinth
H
Hanflik
Andrew M
AM
Wang
Vincent M
VM
Fallon
John T
JT
Ehrlich
H Paul
HP
D000375:Aging / Q000235:genetics* / Q000473:pathology* / Q000502:physiology; D000818:Animals; D001696:Biomechanical Phenomena; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D054411:Receptors, Leptin / Q000235:genetics*; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology
D001786:Blood Glucose; D006442:Glycated Hemoglobin; D054411:Receptors, Leptin; C515447:leptin receptor, mouse