Evidence verdict: Circadian biology is a useful framework for understanding timing in physiology and health. A rhythm measurement is context-dependent, and improving one sleep or timing outcome does not by itself demonstrate slower biological aging or longer life.
Evidence verdict: Immunosenescence is a real, multi-component feature of aging associated with reduced vaccine responsiveness, impaired immune surveillance and higher vulnerability to infection. Thymic involution contributes importantly to declining naïve T-cell production, but immune aging also reflects hematopoietic, metabolic, inflammatory and cellular-senescence changes. Human immune-rejuvenation strategies remain experimental;…
Evidence verdict: Chronic, low-grade systemic inflammation is strongly associated with aging and many age-related diseases, and current geroscience treats inflammaging as a convergence point linking senescence, immune dysregulation, mitochondrial stress and environmental exposures. Yet there is no single validated inflammaging test or universally safe anti-inflammatory longevity therapy. The…
Evidence verdict: Loss of proteostasis is a recognized hallmark of aging and is supported by mechanistic work across model systems and by human tissue evidence. A 2025 Cell atlas of 516 samples across 13 human tissues found widespread transcriptome–proteome decoupling, proteostasis decline and age-related amyloid accumulation. However, most…
Evidence verdict: DNA methylation and other epigenetic patterns change reproducibly with age, and some methylation-based clocks predict morbidity and mortality risk. Human interventions can shift certain clocks, but responsiveness varies substantially by clock and intervention. The 2026 TranslAGE analysis of 51 longitudinal studies found stronger and more consistent…
Evidence verdict: Sirtuins are deeply involved in metabolism, DNA repair, mitochondrial function, inflammation and stress responses, and several sirtuins modify lifespan or healthspan in model organisms. Human genetics and small cohort studies support biological relevance, especially for SIRT6, but no intervention has shown that activating a sirtuin extends…
Evidence verdict: Cellular senescence is a heterogeneous family of stress-associated cell states, not a single uniform cell type. Transient senescence can support wound healing, development and tumor suppression, whereas persistent senescent cells and their secretory programs can contribute to chronic inflammation and tissue dysfunction. Human translation is limited…
Evidence verdict: Autophagy is fundamental to cellular maintenance and is required for many lifespan-extending interventions in model organisms. Human studies can measure selected components and intervention-related signals, but no validated clinical threshold shows that more autophagy equals slower human aging or longer lifespan.
Evidence verdict: Mitophagy is a central mitochondrial quality-control process associated with aging and age-related disease. Some interventions alter mitophagy-related markers in humans, but proving that increasing completed mitophagic flux slows human aging remains a major translational challenge.
Evidence verdict: Mitochondrial aging is not simply “less ATP.” It involves interacting failures in quality control, dynamics, proteostasis, mitophagy, biogenesis, redox signaling, mitochondrial DNA integrity and inflammatory signaling. These defects are strongly linked to age-related functional decline, but no single mitochondria-targeted intervention has yet been proven to broadly…