A review from Wrocław proposes testing the hypothesis that aging is a wound that never begins to heal by measuring the speed and completeness of tissue recovery after a defined injury
A review from Wrocław proposes testing the hypothesis that aging is a wound that never begins to heal by measuring the speed and completeness of tissue recovery after a defined injury
On October 10, Piotr Paweł Chmielewski and Bartłomiej Strzelec of Wroclaw Medical University published a review in the International Journal of Molecular Sciences. They suggest that some age-related impairments arise when tissue repair stalls midway: dead cells remain uncleared, and inflammation persists.
Vienna-based researcher Mikołaj Ogrodnik proposed the hypothesis that aging is a wound that never begins to heal in Nature Communications in 2025. He noted that inflammation and senescent cells (cells that no longer divide and release inflammatory substances) persist in aging skin, liver, and brain tissue, resembling the inflammatory phase of wound healing. Ogrodnik proposed that repair had become stuck in this phase.
Chmielewski and Strzelec propose assessing tissue damage, repair capacity, and residual loss of function separately to distinguish inadequate repair from excessive damage. In their view, tissue resilience is reflected in its response to a defined injury: the peak response, the rate at which it subsides, and the completeness of recovery.
Derek Gilroy’s group at University College London described such measurements in humans in Nature Immunology in 2020. They applied cantharidin, a blistering agent, to the forearms of volunteers aged 18–40 and over 65. After one day, neutrophil (white blood cell) counts in the blisters were similar in both groups; by the third day, counts had fallen in younger participants but remained unchanged in older participants. Macrophages (cells that clear cellular debris) from older participants were less able to bind dying cells: elevated activity of the enzyme p38 left them with insufficient TIM-4 receptor. Eleven older participants took losmapimod, a p38 inhibitor, before cantharidin application. In the samples tested, the receptor was restored, and fewer dying neutrophils accumulated than in participants who had not taken the drug, although neutrophil influx and levels of two inflammatory proteins in the blisters were unchanged.
An experiment at Stanford University published in Science showed that impaired clearance contributes to organ aging in mice. Researchers disabled EP2, a receptor that inhibits the clearance of senescent neutrophils, in tissue macrophages. As these mice aged, clearance continued, and memory and muscle mass were preserved.
According to the review, treatment choice depends on the tissue’s main measurable defect (excessive damage, senescent cells, or impaired clearance) and on timing: suppressing an early protective response can hinder repair, whereas correcting a prolonged response may help. Senolytics, drugs that target senescent cells, “induce death in susceptible senescent cells but do not themselves clear the resulting cellular material,” the authors write. When clearance is inadequate, dead cell remnants and secondary inflammatory signals may take the place of living senescent cells.
The hypothesis would be weakened if a prolonged response to injury failed to predict functional decline; if the rate of recovery added no predictive value beyond “aging clocks” (estimates of biological age based on DNA marks) and similar measures; or if a drug that demonstrably engaged its target and corrected a repair defect repeatedly failed to improve tissue function.
According to the review, trials should enroll people with a confirmed repair defect and assess success by the recovery of tissue function. Lower inflammatory markers and a younger molecular age remain intermediate measurements: in a Harvard Medical School preprint, clocks based on gene activity estimated that mouse intestinal epithelium at the peak of healing was younger than uninjured epithelium.