Background: As a result of the attacks on September 11, 2001, the entirety of lower Manhattan was consumed by a dust cloud containing numerous biological hazards. World Trade Center (WTC) responders who were present at the time of the collapse and cleanup were exposed to these toxins and carcinogens. Because aging acceleration is known to occur in response to some environmental exposures as well as trauma, we hypothesize that WTC exposures may have led to premature biological aging, although the impact of WTC exposure on aging is underexplored.
 
Objectives: To analyze the effect of WTC exposure on accelerated aging by studying the biological aging profiles of prostate cancer tissue, thyroid cancer tissue, and normal tissue samples.
 
Methods: Tissue samples were collected from WTC-exposed prostate (n = 10) and thyroid tumors (n = 32) and frequency matched to unexposed prostate (n = 11) and thyroid tumors (n = 37). Samples were also obtained from histologically normal thyroid tissue of WTC-exposed (n = 14) and unexposed (n = 19) subjects. RNA sequencing was performed for each tissue sample, and biological age was estimated using a transcriptomic aging model. Aging acceleration was calculated as the residuals from a linear regression of biological age on chronological age, to quantify how much an individual’s biological age deviates from what is expected based on their chronological age. The association between WTC exposure and aging acceleration in prostate and thyroid cancer tissues was evaluated using linear regression adjusting for tissue type. An aging acceleration by exposure linear regression model was separately performed on the normal thyroid tissue samples. Aging acceleration distributions were compared across exposure groups within each tissue type using Wilcoxon rank-sum tests.
 
Results: WTC-exposed samples showed higher aging acceleration differences than controls across all three tissue types, with significantly different distributions among normal and tumor thyroid tissues (p = 0.024, p = 0.011 respectively). WTC-exposed tumor tissue samples showed higher aging acceleration compared with the controls (β = 5.41, 95% CI: 1.47–9.36, p = 0.007). WTC exposure was also associated with higher aging acceleration in normal thyroid tissue (β = 5.337, 95% CI: 0.168–10.5, p = 0.0434).

Conclusions: WTC exposure corresponded to higher aging acceleration compared with unexposed controls. This was true for cancer as well as normal tissues. The consistent trend across all tissue types suggests that WTC exposure may influence accelerated aging. These findings are aligned with results from a prior study conducted among 9/11 survivors, which found that WTC exposed females had an average of +6 years accelerated aging compared to unexposed females. The observed accelerated biological aging could play a role in the increase in cancer rates and other morbidities observed in WTC responders.

Accelerated Aging in World Trade Center Responders