“While the in vivo effects of DMA are yet to be fully explored, our findings suggest that it might represent a new, clinically viable way to combat cancer and senescence without toxicity to healthy cells and tissues.”
BUFFALO, NY — August 3, 2026 — A new research paper was published in Volume 18 of Aging on July 17, 2026, titled “Selective targeting of cancer and senescence via shared metabolic shifts extends lifespan of old mice.”
The study was led by first author Zachery R. Robinson, and corresponding author and Aging editorial board member Irina M. Conboy, both from the Department of Bioengineering and QB3 Institute, University of California, Berkeley. The researchers developed a new combination therapy that selectively targets both cancer cells and senescent cells by exploiting metabolic vulnerabilities shared by these two cell types. In laboratory studies and aged mice, the treatment selectively eliminated senescent cells and reduced cancer cell viability while improving physical performance and extending lifespan without significant toxicity to healthy tissues.
Cancer and aging are closely linked. As people age, senescent cells accumulate throughout the body. Although these cells no longer divide, they remain metabolically active and release inflammatory molecules known as the senescence-associated secretory phenotype (SASP), which contributes to chronic inflammation, tissue dysfunction, and tumor progression. Existing therapies such as the BCL-2/BCL-xL inhibitor navitoclax (ABT-263) can eliminate both cancer cells and senescent cells but require doses that frequently cause thrombocytopenia, a potentially serious reduction in platelet counts that has limited their clinical use.
To overcome these limitations, the investigators developed a three-drug combination called DMA, consisting of dichloroacetate (DCA), metformin, and a ten-fold lower dose of navitoclax than is typically used. They tested the treatment across multiple human senescent cell models, several human cancer cell lines, healthy primary human cells, and aged mice. DMA selectively eliminated senescent cells induced by different mechanisms while sparing healthy fibroblasts, neural precursor cells, hepatocytes, and largely preserving human myoblast viability. The combination also effectively reduced the viability of cervical, breast, and colorectal cancer cells, including breast cancer cells that were relatively resistant to navitoclax alone.
The researchers also investigated why DMA selectively affected unhealthy cells. Both senescent cells and many cancer cells have impaired mitochondrial function and altered energy metabolism, making them less able to tolerate additional ATP depletion. The study demonstrated that DMA dramatically depleted ATP levels in senescent and cancer cells while allowing healthy cells to maintain their energy production. Additional metabolic analyses showed that senescent cells lacked the metabolic flexibility needed to compensate for the treatment-induced stress, leading to selective apoptosis and reduced cancer cell proliferation.
When evaluated in aged mice, DMA produced encouraging results beyond the laboratory studies. Short-term treatment significantly improved treadmill endurance without increasing frailty or reducing strength. Longer-term intermittent treatment beginning at approximately 18 months of age extended average post-treatment survival by approximately 102.6 days, representing a 41.7% increase compared with control animals after treatment initiation. Importantly, the reduced-dose combination avoided the marked thrombocytopenia observed with conventional high-dose navitoclax while also shifting circulating inflammatory proteins toward a more youthful profile.
“In summary, this work provides evidence for overlapping, fundamental energy shifts in SnCs and cancer cells, allowing both subsets to avoid apoptosis.”
The authors note that these findings remain preclinical and that additional studies are needed to evaluate the treatment in animal models of spontaneous cancer and age-related diseases before clinical translation. Nevertheless, because metformin and dichloroacetate are already widely used medications and navitoclax has undergone clinical testing, the strategy may provide a practical foundation for developing therapies that simultaneously target cancer and cellular senescence while minimizing toxicity.
Overall, this study identifies a shared metabolic vulnerability between cancer cells and senescent cells that can be exploited therapeutically using a low-dose combination approach. By selectively disrupting energy production in pathological cells while largely sparing healthy tissues, DMA improved physical function and extended lifespan in aged mice, supporting further investigation of this strategy as a potential treatment for aging-related diseases and cancer.
Paper DOI: https://doi.org/10.18632/aging.206399
Corresponding author: Irina M. Conboy – [email protected]
Keywords: senescence, cancer, aging, metabolic shift, ATP
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