Targeting dormant cancer cells cuts recurrence by 80-87% in breast cancer survivors
Targeting dormant cancer cells cuts recurrence by 80-87% in breast cancer survivors
This week brought breakthroughs in targeting the cellular mechanisms that drive aging and disease - from sleeping cancer cells to metabolic clocks that predict how fast we're aging.
๐ฏ Dormant Cancer Cells Successfully Targeted in Breakthrough Trial
Researchers tackled one of cancer's biggest challenges: dormant tumor cells that hide in bone marrow and cause recurrence years later. In a phase 2 trial with 51 breast cancer survivors who had detectable dormant cells, they tested three treatments - hydroxychloroquine (HCQ), everolimus (EVE), or both combined.
The results were striking: 3-year recurrence-free survival rates hit 91.7% for HCQ alone, 92.9% for EVE alone, and 100% for the combination
All three treatments reduced dormant cell counts by 78-87% compared to no treatment, with 98-99.9% probability these reductions were real
The treatments were well-tolerated - only one patient stopped early due to side effects
Why this matters: This is the first human trial to successfully target dormant cancer cells, potentially preventing recurrence in the 30% of breast cancer patients who develop metastases years after initial treatment.
Key Findings
๐งฌ Aging Protein EPS8 Drives Disease-Related Protein Clumps
Scientists discovered that EPS8, a protein that accumulates with age, promotes the toxic protein clumps seen in Huntington's disease and ALS. When they knocked down EPS8 in worms and human cells, it prevented protein aggregation and neurodegeneration. The key regulator? USP4, an enzyme that normally breaks down EPS8 - reducing USP4 during aging prevented EPS8 buildup and extended lifespan.
๐ฌ Asparagine Starvation Selectively Kills Senescent Cells
Researchers found that senescent cells (damaged cells that accumulate with age) have a critical weakness: they can't make their own asparagine amino acid. By combining L-asparaginase (which destroys external asparagine) with autophagy inhibitors (which block internal recycling), they selectively killed senescent cells in aged mice. This dual treatment reduced age-related bone loss, atherosclerosis, and fatty liver disease.
๐ Nerve-Associated Fat Cells Control Aging Inflammation
Using single-cell sequencing, scientists mapped how different fat tissue immune cells change with age. They discovered that CD169+ nerve-associated macrophages (NAMs) decline with aging, and when depleted in old mice, inflammation increased and fat breakdown was impaired. These specialized cells appear to control both tissue inflammation and metabolic function throughout life.
๐งช Engineered Probiotic Yeast Fights Colon Cancer
Scientists engineered Saccharomyces boulardii yeast to secrete spermidine, a longevity-promoting molecule. In mouse models of inflammatory bowel disease and colon cancer, this engineered probiotic significantly outperformed regular S. boulardii in reducing colitis symptoms and preventing cancer development. The modified yeast successfully colonized the gut and raised local spermidine levels.
๐ Mediterranean Diet Evidence Shows Mixed Longevity Results
A comprehensive review challenged the assumption that vegetarian diets automatically increase longevity. While one 'blue zone' (areas with exceptional longevity) is largely vegetarian, most are inhabited by flexitarians who eat some meat. The analysis found a lack of high-quality evidence for vegetarian diets extending telomeres or definitively reducing mortality when objective measures were used.
๐ฌ Metabolic Clocks Predict Biological Age from Blood
Researchers developed new 'metabolomic clocks' that estimate biological age using metabolic markers measurable in blood via NMR spectroscopy. These clocks can identify disease-specific metabolic distortions and support early detection of accelerated aging. The approach combines high accuracy in age prediction with clinical interpretability for risk assessment.
Implications
These studies reveal aging as a highly targetable process - from dormant cancer cells to senescent cell metabolism to inflammatory immune cells. The convergence on autophagy, metabolism, and cellular quality control suggests we're identifying the core mechanisms that could be manipulated to extend healthy lifespan.
Studies in this issue
Primary sources used for this newsletter.
- Stopping inactive tumor cells to help prevent breast cancer from coming back: a phase 2 clinical trialmain storyNature medicine2025-09-02PMID 40897974
- Modified yeast that releases spermidine reduces colon inflammation and cancer in micekey findingScientific reports2025-08-30PMID 40885775
- Removing Aging Cells by Combining Asparaginase and Autophagy Blockers to Cut Asparagine Supplykey findingAging cell2025-09-04PMID 40905331
- Are vegetarian diets good or bad for living longer?key findingMaturitas2025-09-03PMID 40902289
- Aging Clocks Based on Metabolic Chemicalskey findingnpj metabolic health and disease2025-09-03PMID 40903544
- The aging-related protein EPS8 may cause harmful protein clumps by overactivating RAC signalingkey findingNature aging2025-09-03PMID 40903652
- Nerve-related immune cells regulate fat tissue balance throughout life and reduce inflammation with agingkey findingNature aging2025-09-02PMID 40897908
Continue reading
All Longevity & Aging issuesGet the next Longevity & Aging issue
Seven papers, once a week. Free.