Longevity through immunity: the unusual naked mole-rat immune system

Area of Science:

• Immunology
• Comparative Biology
• Longevity Research

Background:

• Naked mole-rats (NMRs) exhibit remarkable longevity and resistance to aging.
• Their immune system is hypothesized to play a crucial role in their healthspan.
• Adult NMRs possess functional thymic tissue, a paedomorphic trait.

Purpose of the Study:

• To investigate the unique immunological characteristics of naked mole-rats.
• To understand how their immune system contributes to their exceptional longevity and healthspan.
• To compare NMR immune cell populations and diversity with those of mice.

Main Methods:

• Transcriptomic analysis of NMR immune cells.
• Comparison of myeloid to lymphoid ratios between NMRs and mice.
• Characterization of T cell populations, including αβ and γδ T cells, in NMRs.

Main Results:

• NMRs have a higher myeloid to lymphoid ratio and lack natural killer (NK) cells compared to mice.
• NMR CD8 T cell clonotypic diversity is limited and less than their CD4 T cells.
• NMRs possess a large circulating population of γδ T cells with distinct subsets, including a cytotoxic subset with a dominant clonotype.

Conclusions:

• The NMR immune system is biased towards innate immune surveillance and cancer protection, rather than viral defense.
• This atypical immune strategy, including a prominent cytotoxic γδ T cell population, likely contributes to their prolonged healthspan and longevity.
• NMRs may have evolved under relaxed viral selective pressure, optimizing their immunity for their specific environment.