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Several interventions have recently emerged that were proposed to reverse rather than just attenuate aging, but the criteria for what it takes to achieve rejuvenation remain controversial. Distinguishing potential rejuvenation therapies from other longevity interventions, such as those that slow down aging, is challenging, and these anti‐aging strategies are often referred to interchangeably. We suggest that the prerequisite for a rejuvenation intervention is a robust, sustained, and systemic reduction in biological age, which can be assessed by biomarkers of aging, such as epigenetic clocks. We discuss known and putative rejuvenation interventions and comparatively analyze them to explore underlying mechanisms., Emerging interventions have suggested that biological aging can be reversed rather than just attenuated, but the criteria for what it takes to achieve rejuvenation remain controversial. In this review, we discuss known and putative rejuvenation interventions, exploring their connections within the context of aging biomarkers. We suggest that the prerequisite for classifying an intervention as rejuvenating is a robust and reproducible reduction in biological age, which can be assessed by high‐dimensional trackers of aging such as epigenetic clocks.

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., Naked mole‐rats do not display thymic involution by 11 years of age, in contrast to continuous thymus shrinkage in mice. The key markers of youthful thymus function Aire and Foxn1 decrease with age in mice, but are maintained in naked mole‐rats. Characterization of organ integrity and function in >30 year‐old naked mole‐rats could provide a blueprint to naturally maintain a healthy thymus.