Ectopic cervical thymi and no thymic involution until midlife in naked mole rats

Abstract

Immunosenescence is a hallmark of aging and manifests as increased susceptibility to infection, autoimmunity, and cancer in the elderly. One component of immunosenescence is thymic involution, age‐associated shrinkage of the thymus, observed in all vertebrates studied to date. The naked mole rat (Heterocephalus glaber) has become an attractive animal model in aging research due to its extreme longevity and resistance to disease. Here, we show that naked mole rats display no thymic involution up to 11 years of age. Furthermore, we found large ectopic cervical thymi in addition to the canonical thoracic thymus, both being identical in their cell composition. The developmental landscape in naked mole rat thymi revealed overt differences from the murine T‐cell compartment, most notably a decrease of CD4+/CD8+ double‐positive cells and lower abundance of cytotoxic effector T cells. Our observations suggest that naked mole rats display a delayed immunosenescence. Therapeutic interventions aimed at reversing thymic aging remain limited, underscoring the importance of understanding the cellular and molecular mechanisms behind a sustained immune function in the naked mole rat.

Characterization of naked mole‐rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits

“…The low HSPC IFN signaling together with largely diminished cytotoxic CD8-TCs may explain the insufficient anti-viral response of NMRs. We also showed that total thymic cellularity was markedly lower in NMRs compared to mice (Emmrich et al, 2021). NMRs may not have evolved to deal with viral challenges because subterranean lifestyle with limited contact outside the native colony limits viral spread.…”

Immune system aging and the aging-related diseases in the COVID-19 era

“…Interestingly, the extremely long-lived subterranean rodent – the naked mole rat – has recently been shown to have not just one mediastinal thymus (as is typical for other mammals including humans), but also a few cervical thymi which apparently ascertain constant provision of new naïve T cells, prevent thymic involution until midlife of the mole rats, and in consequence, produce an extreme resistance of these animals to infections and cancers and increase their longevity [33] . Not surprisingly, this discovery yielded support to the search for ways of rejuvenation of our own thymuses as a way of prolonging healthy life.…”

Single-cell transcriptomics reveals age-resistant maintenance of cell identities, stem cell compartments and differentiation trajectories in long-lived naked mole-rats skin

“…More recently, NMR aged 3 and 11 years were used as compared to mice aged 3 and 12 months. They discovered that NMR owned an additional pair of cervical thymi and that they had no thymic involution up to 11 years of age, suggesting that they displayed a delayed immunosenescence [ 53 ]. Thus, we hypothesize that the maintenance of cellular compartments in the older NMR, especially the stem cell pool through high Igfbp3 expression, coupled with an increase skin immunity, could explain their skin slower rate of aging.…”