Targeting Senescence to Improve Wound Healing in Aging

靶向衰老以改善衰老过程中的伤口愈合

基本信息

  • 批准号:
    10729963
  • 负责人:
  • 金额:
    $ 24.3万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-01 至 2028-05-31
  • 项目状态:
    未结题

项目摘要

Impaired or delayed wound healing is a major problem affecting primarily older adults, millions of older adults in the United States are affected per year. Delayed wound healing increases aged patients’ risk of chronic wounds, wound infections, and tissue necrosis, resulting in significant morbidity and mortality. Wound care is also a rising economic problem with an estimated $10 billion annually spent on wound care for older adults. The various causes for delayed healing of aging ultimately result in perturbations of normal wound healing processes. This includes a recently discovered wound healing response incorporating cellular senescence, a biologically active state of permanent growth arrest caused by various stressors like tissue injury. Senescent cells (SnC) that arise acutely in cutaneous wounds have beneficial effects in wound healing when they are transiently present, however, specific SnC identities and their associated functions during wound healing have still not been thoroughly characterized. My preliminary data generated during my GEMSSTAR award confirm a robust and transient increase in beneficial senescence during excisional wound healing in young (2 month) mice, required for timely wound resolution. However, my data also demonstrates that in aged (24 month) mice with delayed wound healing, this acute wound senescence response is significantly attenuated. A similar diminished acute senescence-like response occurs during aged human wound healing suggesting that attenuation is conserved between species. To gain better understanding of wound SnCs that benefit wound healing and which are diminished in aging, my lab has isolated high-expressing p16Ink4a (a common senescence marker) cells from the wounds of young p16tdTom mice. Preliminary single-cell RNAseq analysis reveals multiple wound cell types with high p16+ expression during wound healing. A majority are within distinct clusters of fibroblasts (Fb) and macrophages (Mϕ) with p16+ expression associated with positive regulation of wound healing: p16+ wound Fbs upregulate genes for protein synthesis and certain collagens while p16+ wound Mϕs are more anti-inflammatory and promote extracellular matrix deposition with both cell types being more apoptosis-resistant compared to their respective p16-negative counterparts. As transient senescence is important for optimal wound healing in younger organisms this project’s goals are to uncover the cellular mechanisms by which specific wound SnCs positively influence wound healing and determine their roles in delayed healing of aging. I will test the overall hypothesis that age-related attenuation of beneficial wound SnCs contributes to delayed wound healing in aged mammals and that restoration of these key wound SnCs can promote more timely wound resolution. The following Aims are designed to elucidate changes in wound SnCs throughout aging, define their beneficial impact on wound healing, and provide the therapeutic framework for treatment of delayed healing of aging with senescence modification.
伤口愈合受损或延迟是主要影响老年人的主要问题

项目成果

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Daniel Sam Roh其他文献

Daniel Sam Roh的其他文献

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{{ truncateString('Daniel Sam Roh', 18)}}的其他基金

Role of Senescence in the Impaired Wound Healing of Aging
衰老在衰老伤口愈合受损中的作用
  • 批准号:
    10027701
  • 财政年份:
    2020
  • 资助金额:
    $ 24.3万
  • 项目类别:
Role of Senescence in the Impaired Wound Healing of Aging
衰老在衰老伤口愈合受损中的作用
  • 批准号:
    10251307
  • 财政年份:
    2020
  • 资助金额:
    $ 24.3万
  • 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
  • 批准号:
    8215633
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
  • 批准号:
    8044043
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
  • 批准号:
    7805954
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:
Homeostatic Roles of Connexin43 in Response to DNA Damage
Connexin43 在 DNA 损伤反应中的稳态作用
  • 批准号:
    8403696
  • 财政年份:
    2010
  • 资助金额:
    $ 24.3万
  • 项目类别:

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