An Age-Associated Decline in Thymic Output Differs in Dog Breeds According to Their Longevity

Abstract

The age associated decline in immune function is preceded in mammals by a reduction in thymic output. Furthermore, there is increasing evidence of a link between immune competence and lifespan. One approach to determining thymic output is to quantify signal joint T cell receptor excision circles (sj-TRECs), a method which has been developed and used in several mammalian species. Life expectancy and the rate of aging vary in dogs depending upon their breed. In this study, we quantified sj-TRECs in blood samples from dogs of selected breeds to determine whether there was a relationship between longevity and thymic output. In Labrador retrievers, a breed with a median expected lifespan of 11 years, there was an age-associated decline in sj-TREC values, with the greatest decline occurring before 5 years of age, but with sj-TREC still detectable in some geriatric animals, over 13 years of age. In large short-lived breeds (Burnese mountain dogs, Great Danes and Dogue de Bordeaux), the decline in sj-TREC values began earlier in life, compared with small long-lived breeds (Jack Russell terriers and Yorkshire terriers), and the presence of animals with undetectable sj-TRECs occurred at a younger age in the short-lived breeds. The study findings suggest that age-associated changes in canine sj-TRECs are related to breed differences in longevity, and this research highlights the use of dogs as a potential model of immunosenescence.

The Effects of Tissue Regenerative Status on Hormesis in Dogs Irradiated during Their Lifespan

“…This may partly explain why anemia was not noted in WO animals ( -3) [21]. At this time, thymus function ceases in dog breeds [43]. This dramatic decline in hormesis at 10 years (Figure 3) indicates that the process is dependent on morphogenic cells that are of lymphocytopoietic origin.…”

Polymorphisms in the canine IL7R 3′UTR are associated with thymic output in Labrador retriever dogs and influence post-transcriptional regulation by microRNA 185

“…Since the formation of sj-TREC occurs specifically in the thymus and this DNA does not replicate, sj-TREC has been used as a biomarker for thymic output/RTEs in a wide range of species, including humans (Douek et al, 1998), mice (Sempowski et al, 2002), primates (Sodora et al, 2000), chickens (Kong et al, 1999) and pigs (Vallabhajosyula et al, 2011). In Labrador retriever dogs an ageassociated decline in sj-TREC values was observed which appear to be bi-phasic in nature, with differences occurring between different age groups, and has been previously described (Holder et al, 2016). This is similar to that seen in humans, where the greatest decline in sj-TRECs occur between the teenage years and middle age (40-50 years) (Geenen et al, 2003), subsequently, sj-TREC values show a slow decline between the 6 th and 9 th decades of life before decreasing significantly in the 10 th decade (Mitchell et al, 2010).…”

“…The association between sj-TREC and IL7R genotypes also suggests a relationship between IL-7R expression and thymic involution. Human longitudinal studies have shown that sj-TREC values decline by an average of 3% of the baseline level per year (Kilpatrick et al, 2008), while a recent study in dogs suggests that differences in sj-TREC levels observed between individual young Labrador retrievers might be indicative of the rate of thymic involution (Holder et al, 2016). In mouse strains which undergo rapid thymic involution, as determined by an earlier decline in sj-TREC values, developing thymocytes were found to have increased expression of IL-7R, compared to those mouse strains demonstrating a slower rate of thymic involution (Wang et al, 2006).…”

“…Genomic DNA samples from the 100 Labrador retrievers were used to quantify sj-TREC expression by real-time qPCR as previously described by Holder et al (Holder et al, 2016).…”

“…These small episomal circles of DNA are generated during T cell development, when the T cell receptor (TCR)  gene segments, positioned within the TCR α locus, are excised as a prelude to VDJ recombination (de Villartay et al, 1988;Hockett et al, 1988). In a recent study (Holder et al, 2016), we have demonstrated that this technique can be applied in dogs, and that there is an ageassociated decline in sj-TREC values. This suggests that in dogs, there is a reduction in the number of recent thymic emigrants (RTEs) with increasing age, which is similar to that observed in humans (Douek et al, 1998) and mice (Sempowski et al, 2002).…”