🔬TODAY’S BREAKTHROUGH
Aging doesn’t just slow you down, it silences your immune defense.
The Discovery:
A new study reveals that declining leptin levels with age drive the senescence of CD8+ T cells inside tumors. Leptin, a hormone produced by fat cells, protects T cells from aging by blocking p38 MAPK signaling. When leptin drops, as it naturally does in older adults, tumor-infiltrating T cells lose function, accelerate senescence, and allow cancers to grow unchecked. Boosting leptin restored immune function and improved survival in aged mice.
The Science:
Senescent CD8+ T cells increase with age inside tumors in humans and mice, marked by high p16 and poor survival
Systemic leptin levels decline with age, especially in lean older individuals
Leptin treatment rejuvenated T cells, reduced p16 expression, and restored IFN-γ production in aged tumor-bearing mice
Mechanism: Leptin blocks p38 MAPK, preventing T cell senescence at the transcriptional and protein levels
Mice with leptin receptor knockout in T cells showed higher tumor burden, early death, and more T cell senescence
Orlistat-induced fat loss reduced leptin and worsened T cell aging, despite reducing fat mass
Human cancer patients (CRC, LC, RCC): low plasma leptin strongly correlated with higher intratumoral p16+ CD8+ T cell levels
Moderate BMI and healthy adipose tissue preserved leptin and limited immune aging
Your Action:
This study is not about obesity, it’s about avoiding excess fat loss that strips away immune-supportive leptin. Support healthy leptin levels with stable body composition, anti-inflammatory eating, resistance training, and avoiding chronic caloric deprivation. Talk to a physician before experimenting with leptin-related interventions, but don’t ignore fat loss side effects in later life.
Bottom Line:
Age-related leptin decline drives T cell aging in tumors, and restoring it may slow immune senescence.
Source:
An age-related decrease in leptin contributes to CD8+ T cell aging in the tumor microenvironment, Cell Reports Medicine, Wang et al., Shanghai Jiao Tong University
https://doi.org/10.1016/j.xcrm.2025.102310
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.