Non‐homologous end joining (NHEJ) is the principal repair mechanism used by mammalian cells to cope with double‐strand breaks (DSBs) that continually occur in the genome. One of the key components of the mammalian NHEJ machinery is the DNA‐PK complex, formed by the Ku86/70 heterodimer and the DNA‐PK catalytic subunit (DNA‐PKcs). Here, we report on the detailed life‐long follow‐up of DNA‐PKcs‐defective mice. Apart from defining a role of DNA‐PKcs in telomere length maintenance in the context of the ageing organism, we observed that DNA‐PKcs‐defective mice had a shorter life span and showed an earlier onset of ageing‐related pathologies than the corresponding wild‐type littermates. In addition, DNA‐PKcs ablation was associated with a markedly higher incidence of T lymphomas and infections. In conclusion, these data link the dual role of DNA‐PKcs in DNA repair and telomere length maintenance to organismal ageing and cancer.
Aging involves a deterioration of cell functions and changes that may predispose the cell to undergo an oncogenic transformation. The carcinogenic risks following radiation exposure rise with age among adults. Increasing inflammatory response, loss of oxidant/antioxidant equilibrium, ongoing telomere attrition, decline in the DNA damage response efficiency, and deleterious nuclear organization are age-related cellular changes that trigger a serious threat to genomic integrity. In this review, we discuss the mechanistic interplay between all these factors, providing an integrated view of how they contribute to the observed age-related increase in radiation sensitivity. As life expectancy increases and so it does the medical intervention, it is important to highlight the benefits of radiation protection in the elderly. Thus, a deep understanding of the mechanistic processes confining the threat of aging-related radiosensitivity is currently of foremost relevance.
The effect of breed-production system on the myosin heavy chain 1 (MHC-I), the biochemical characteristics and the colour variables of longissimus thoracis (LT) from seven beef breeds was studied: Asturiana de la Montaña (AM), Asturiana de los Valles (AV), Avileña-Negra Ibérica (A-NI), Bruna dels Pirineus (BP), Morucha (MO), Pirenaica (PI) and Retinta (RE) (Age at slaughter between 368 and 541 days; carcass weight between 249 and 334 kg). Significant differences between breed-production systems were found for all traits evaluated. LT from the MO, a rustic type breed, was the most oxidative (MHC-I, 39.3%; isocitrate dehydrogenase activity, 52 nmol min(-1) mg(-1); pigment content, 188.4 μg acid haematin g(-1)) and showed a low L* value (32.6) and high a* and C* values (24 and 27.2, respectively). In terms of meat colour (L* and a*) the canonical discriminant analysis separated the breeds into two groups, the AV, the PI and the A-NI (the lightest ones) from the AM and the MO breeds (the reddest and darkest) whereas the BP showed an intermediate position. The RE and the A-NI were distinguished from the others by their high intramuscular fat content. Meat colour was affected by the muscle biochemical traits in the breed-production systems studied.