Elderly cancer patients treated with ionizing radiation (IR) or chemotherapy experience more frequent and greater normal tissue toxicity relative to younger patients. The current study demonstrates that exponentially growing fibroblasts from elderly (old) male donor subjects (70, 72, 78 years) are significantly more sensitive to clonogenic killing mediated by platinum-based chemotherapy and IR, (~70-80% killing) relative to young fibroblasts (5 months and 1 year; ~10-20% killing) and adult fibroblasts (20 years old; ~10-30% killing). Old fibroblasts also displayed significantly increased (2-4 fold) steady-state levels of O2(·-), O2 consumption, and mitochondrial membrane potential as well as significantly decreased (40-50%) electron transport chain (ETC) complex I, II, IV, V, and aconitase (70%) activities, decreased ATP levels, and significantly altered mitochondrial structure. Following adenoviral-mediated overexpression of SOD2 activity (5-7 fold), mitochondrial ETC activity and aconitase activity were restored, demonstrating a role for mitochondrial O2(·-) in these effects. Old fibroblasts also demonstrated elevated levels of endogenous DNA damage that were increased following treatment with IR and chemotherapy. Most importantly, treatment with the small-molecule, superoxide dismutase (SOD) mimetic (GC4419; 0.25 µM), significantly mitigated the increased sensitivity of old fibroblasts to IR and chemotherapy and partially restored mitochondrial function without affecting IR or chemotherapy-induced cancer cell killing. These results support the hypothesis that age-associated increased O2(·-) and resulting DNA damage mediate the increased susceptibility of old fibroblasts to IR and chemotherapy and can be mitigated by GC4419.
Pharmacology, Toxicology and Pharmaceutical Science
2
7%
Other
3
10%
Unknown
10
33%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 18. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 February 2026.
All research outputs
#2,490,364
of 33,493,714 outputs
Outputs from Cancer Research
#1,780
of 34,193 outputs
Outputs of similar age
#36,020
of 349,494 outputs
Outputs of similar age from Cancer Research
#24
of 153 outputs
Altmetric has tracked 33,493,714 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 92nd percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 34,193 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.3. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 349,494 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 89% of its contemporaries.
We're also able to compare this research output to 153 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 84% of its contemporaries.
