Core Viewpoint - CAR-T cell therapy is one of the most promising cancer treatment methods, but its efficacy is significantly limited by aging-related factors, particularly the decline in nicotinamide adenine dinucleotide (NAD) levels, which drives CAR-T cell failure [2][8]. Group 1: Research Findings - A study published by researchers from the University of Lausanne and Geneva University Hospitals indicates that restoring NAD levels can enhance the therapeutic effects of aging CAR-T cells, providing a promising approach to improve CAR-T therapy [2][8]. - The study demonstrates that aging is a limiting factor for effective CAR-T cell responses, with evidence showing that CAR-T cells derived from aged female mice exhibit mitochondrial dysfunction due to NAD depletion, leading to poor stem-like characteristics and impaired anti-tumor function [7][8]. - Human data analysis further supports that both age and NAD metabolism influence the response to CAR-T cell therapy, highlighting the potential of targeting NAD pathways to restore mitochondrial health and function in CAR-T cells from older patients [7][8]. Group 2: Importance of NAD in T Cell Function - NAD metabolism plays a critical regulatory role in T cell fate and function, with alterations in NAD homeostasis linked to impaired T cell responses [5][6]. - Aging is a primary risk factor associated with cancer, with approximately 75% of cancer patients eligible for immunotherapy being over 65 years old, indicating the need for strategies that address age-related declines in treatment efficacy [5][6]. - The maintenance of stem cell-like T cell populations is crucial for the success of CAR-T cell therapy, and recent studies suggest that enhancing mitochondrial metabolism through metabolic interventions can improve CAR-T cell efficacy [4][8].

Core Viewpoint - The recent study challenges the belief that NAD+ depletion significantly impacts muscle function and accelerates aging, suggesting that muscle health may not be as dependent on NAD levels as previously thought [2][5][11]. Group 1: Study Findings - The study utilized an inducible skeletal muscle-specific Nampt gene knockout (iSMNKO) mouse model, resulting in an 85% reduction in NAD+ levels without affecting muscle mass, integrity, contraction strength, or exercise performance [2][9]. - Even with lifelong NAD+ depletion, the mice did not exhibit accelerated muscle aging or systemic metabolic impairment [8][9]. - The research indicates that skeletal muscle can tolerate significant NAD+ depletion without losing functionality or accelerating aging, contradicting the common belief that NAD+ reduction is a primary driver of muscle aging and weakness [5][11]. Group 2: Implications for NAD+ Supplementation - The findings raise questions about the efficacy of NAD+ supplementation as an anti-aging strategy, suggesting that it may be a waste of resources [5][11]. - The study's leader emphasized that the results challenge the notion that reduced NAD+ levels are a major factor in muscle aging and weakness [5][11]. - The research highlights the need for further investigation into the extent to which NAD+ reduction affects mitochondrial function and the aging process [6][11].