In this issue of Blood, Liu et al provide the first genetic evidence that pl6 defines a lymphoid lineage intrinsic gatekeeper, which prevents B-lymphocyte transformation but impairs T-lymphocyte function in aging mice.Imagine if we could influence our immune system to produce youthful numbers of highly functional lymphocytes throughout life up to a very advanced age, without increasing the risk of tumors derived from the lymphoid lineage. It is conceivable that such an intervention would reduce the risk of deleterious infections and cancer. To therapeutically target the immune system to prevent aging-associated declines in immune function, it is of utmost importance to identify molecular causes of this process. Molecular mechanisms that limit cell proliferation (eg, telomere shortening) have been implemented in cancer protection, but were also shown to contribute to the decline in tissue maintenance and regeneration during aging.
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