A three-drug combination that exploits a metabolic weakness shared by cancer cells and senescent cells has extended post-treatment survival and improved physical performance in aged mice, according to a new study published in Aging-US. The experimental therapy, called DMA, combines dichloroacetate, metformin and a dose of the senolytic drug navitoclax that is approximately ten times lower than doses commonly used in previous studies. The researchers say the approach selectively stressed unhealthy cells while largely sparing healthy tissues, raising the possibility of a new strategy against both cancer and age-related cellular dysfunction.
The study, titled “Selective targeting of cancer and senescence via shared metabolic shifts extends lifespan of old mice,” was led by Zachery R. Robinson, with Irina M. Conboy as corresponding author. Both researchers are affiliated with the Department of Bioengineering and the QB3 Institute at the University of California, Berkeley. Their work addresses a major challenge in aging biology: senescent cells accumulate over time, remain metabolically active and release inflammatory factors known collectively as the senescence-associated secretory phenotype, or SASP. These signals can damage neighboring tissues, promote chronic inflammation and create an environment that supports tumor development.
Senescent cells and cancer cells are biologically different, but many share a critical vulnerability. Their mitochondria and energy-producing pathways are frequently impaired or rewired, leaving them dependent on limited metabolic reserves. Unlike healthy cells, which can often switch between fuel sources when energy production is disrupted, these damaged or rapidly proliferating cells may have little capacity to compensate for a sudden decline in ATP, the molecule that powers most cellular processes. The researchers designed DMA to intensify this energy crisis selectively, pushing vulnerable cells toward apoptosis while allowing healthy cells to preserve their energy balance.
Each component of DMA contributes to the metabolic pressure. Dichloroacetate inhibits pyruvate dehydrogenase kinase, an enzyme that regulates the entry of pyruvate into mitochondrial oxidation and can alter how cells use glucose. Metformin, widely prescribed for type 2 diabetes, can reduce mitochondrial respiratory activity and limit ATP production under certain conditions. Navitoclax blocks anti-apoptotic members of the BCL-2 protein family, lowering the threshold for programmed cell death. Used together, the drugs were intended to weaken energy production and simultaneously remove part of the molecular protection that allows senescent and cancer cells to survive.
The investigators tested DMA in several human cellular systems, including senescent cells generated through different biological mechanisms and cancer cell lines derived from cervical, breast and colorectal tumors. The treatment reduced the viability of these unhealthy cells while sparing healthy primary fibroblasts, neural precursor cells and hepatocytes. Human myoblasts, which develop into muscle cells, were also largely preserved. Notably, the combination affected breast cancer cells that showed relative resistance to navitoclax alone, suggesting that the metabolic agents may increase the effectiveness of the apoptosis-targeting drug.
Laboratory analyses supported the proposed mechanism. DMA caused a pronounced depletion of ATP in senescent and cancer cells, whereas healthy cells were better able to maintain energy production. The researchers concluded that senescent cells lacked sufficient metabolic flexibility to redirect energy generation when the treatment disrupted their normal pathways. This imbalance activated apoptosis and reduced cancer-cell proliferation. The findings suggest that the therapy does not simply identify senescent or malignant cells through a single surface marker; instead, it exploits the functional consequences of mitochondrial dysfunction and altered metabolism.
The team then evaluated DMA in aged mice. In a short-term experiment, animals receiving the combination showed a significantly greater improvement in treadmill running time than control animals treated with solvent. The therapy did not produce a measurable advantage in hanging-test performance, a test of muscular endurance and grip, and it did not significantly alter frailty scores. These results indicate that the immediate functional benefits were selective rather than a broad reversal of every age-related physical deficit. The authors also assessed blood proteins and observed changes in several inflammatory factors associated with the SASP, shifting the circulating profile toward a more youthful pattern.
A longer-term experiment produced the most striking result. Intermittent DMA treatment began when the mice were approximately 18 months old, an age corresponding to advanced adulthood in laboratory animals. After treatment began, the mice receiving DMA lived an average of 102.6 days longer than controls, representing an increase of approximately 41.7 percent in post-treatment survival. The researchers reported no marked thrombocytopenia, the dangerous decline in platelet numbers that has limited the use of conventional high-dose navitoclax. Reducing the navitoclax dose while reinforcing its activity through metabolic stress may therefore be central to the treatment’s apparent tolerability.
The findings remain preliminary and cannot yet establish whether DMA would extend healthy lifespan or treat cancer in humans. The animal survival groups were small, and the experiments did not use mice carrying spontaneous cancers or models that reproduce the full complexity of age-related disease. Additional studies will be needed to determine how the drugs interact over longer periods, whether the treatment affects different organs or tumor types, and whether subtle toxicities emerge with repeated dosing. Even so, the study offers a potentially important framework: rather than targeting cancer and senescence separately, a carefully calibrated metabolic intervention may attack both through their shared dependence on compromised energy systems. With metformin and dichloroacetate already used clinically for other indications, and navitoclax having undergone human testing, the researchers say DMA could provide a practical starting point for future translational research.
Subject of Research: Animals
Article Title: Selective targeting of cancer and senescence via shared metabolic shifts extends lifespan of old mice
News Publication Date: August 3, 2026
Web References: https://doi.org/10.18632/aging.206399; https://www.aging-us.com/figure/206399/f4
References: Robinson Z. R. et al., “Selective targeting of cancer and senescence via shared metabolic shifts extends lifespan of old mice,” Aging-US, published July 17, 2026. DOI: 10.18632/aging.206399
Image Credits: Copyright © 2026 Robinson et al., released under the Creative Commons Attribution License (CC BY 4.0).
Keywords: senescence, cancer, aging, metabolic shift, ATP, senolytics, mitochondria, metformin, dichloroacetate, navitoclax, lifespan extension, cellular metabolism
Tags: bioengineering approaches to extend lifespancancer cell metabolismcombination drug therapy for age-related diseasesdual targeting of cancer and cellular senescenceinnovative strategies for cancer and aginglifespan extension in aged micelow-dose navitoclax for senolytic treatmentmetabolic vulnerabilities of cancer and senescent cellssenescence-associated secretory phenotype (SASP)senolytic therapy in agingtargeting inflammatory factors in agingtargeting senescent cells to improve physical performance
