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Last Updated:
06 February 2026 - 09:25 AM
Perspectives on Aging Research and the Near Future of the Field 05 February 2026 - 07:22 PM
Aging research is not a field marked by its unity. At the high level there is some degree of consensus on the need to treat aging as a medical condition, and that this is a plausible goal given time and effort. But ask questions about any particular detail regarding the mechanisms of aging, how to progress towards therapies, the bounds of the possible, and the state of the field, and you will usually find almost as many opinions as there are researchers to hold them. This is characteristic of a field of study in which far more remains to be discovered than has been mapped to date. The research community cannot be said to fully understand the cell, let alone how an organism made up countless cells of many diverse types changes over time.
Still, enough is known to make inroads. We can target senescent cells for selective destruction. We can replace mitochondria. We can reprogram epigenetic patterns. And so forth. We can have opinions on how well any specific class of therapy will perform, but only by earnestly trying a given approach - building the therapies, conducting the clinical trials, and bringing drug into widespread use - will we actually find out how well that approach works.
As recent history demonstrates, the creation of novel therapies is a slow process in the present environment of medical regulation. Ten years is a rapid pace for the move from idea to first clinical trial. Another decade might pass between that first trial and commercial availability of the resulting drug for the average patient. Success for any given line of research is not inevitable. Viable therapies can be completely ignored because the drugs involved are generic, or the approach otherwise cannot be effectively patented and monopolized. A long road lies ahead, given the way in which medical research and development is presently conducted.
Past, present and future perspectives on the science of aging
Juan Carlos Izpisua Belmonte: In the next decade, I expect aging research to move from describing decline to restoring function. High-resolution human datasets, from single-cell and spatial maps to longitudinal studies, will provide a clearer picture of how aging progresses across tissues. At the same time, systemic biology will become even more important, with interorgan communication and circulating signals serving as key therapeutic entry points. Clinically, biological age measures will help to personalize prevention and allow earlier intervention. In the long term, I am hopeful that these developments will reshape medicine.
Steve Horvath: Over the next 10 years, I expect the field to shift decisively from measuring aging to modulating it in humans. I hope that epigenetic clocks will continue to mature into tools for evaluating interventions in individuals and even at population scale. My hope is that the aging field will identify safe, well-tolerated interventions that are capable of rejuvenating multiple human organ systems.
Bérénice A. Benayoun: In the next decade, I think the future of our field will be precision geroscience - understanding what shapes aging trajectories and which levers can be potentially acted upon to promote long-term health, not only based on private unique genetic variation but also other important factors that we are just beginning to appreciate/
Steve N. Austad: I see a takeover by massive omics. I am not suggesting this is a bad thing. It will certainly lead to a personalization of health and medical treatments, but I don't think it will lead to the kind of breakthrough that something like antibiotics represented. I think there will be more interventions on the market over that time (mostly supplements) - some might even be effective, although I doubt they will outdo what the best lifestyle choices do now. Real breakthroughs, if they come, will be further out than 5-10 years.
Terrie E. Moffitt: Over the next 5-10 years, I envision aging research evolving into an era of close integration between basic and clinical sciences, much like what has been achieved in hypertension, diabetes and cancer research. As our understanding of the molecular mechanisms that regulate aging deepens, we will see the identification of diverse therapeutic targets and an acceleration in the development of drugs, vaccines and other interventional strategies.
Guang-Hui Liu: The coming decade will probably see a shift towards precision geroscience. Multidimensional aging clocks may become clinically useful tools for quantifying biological age and intervention effects. We anticipate early human trials targeting newly recognized aging drivers, and advances in gene and cell-based regenerative strategies. Critically, the field is moving towards a unified medical paradigm: targeting the root causes of aging to prevent multiple chronic conditions together, rather than individually.
Vadim N. Gladyshev: I expect to see organ- and systems-resolved aging maps and clinically qualified aging biomarkers; routine real-time biological age monitoring (omics, digital, wearables, and imaging); embryo-inspired rejuvenation cues; advances in replacement; insights from long-lived species on complex interventions that slow down aging; and advances in the theoretical understanding of aging.
Vera Gorbunova: I expect the first antiaging interventions to be approved and introduced to clinical practice. I see aging biomarkers to become a routine part of a health check-up linked to individualized recommendations on improving healthspan. I also expect the development of safe interventions focused on restoring a more youthful epigenome, and preventative strategies to enhance genome stability and improve DNA repair to become available.
David A. Sinclair: I expect the emergence of interventions that treat common diseases by resetting cellular age and allowing the body to heal itself. This will include Yamanaka factor mediated epigenetic reprogramming, due to be tested in humans in 2026, followed by epigenetic editing, small-molecule reprogramming drugs and AI-guided therapies. Within 10 years, I foresee whole-body rejuvenation.
George A. Kuchel: I firmly believe that the future of geroscience, and also its most important impact, will be in the prevention of multiple chronic conditions, which are among the most prevalent and typical features of aging in humans.
John W. Rowe: First, there will be a dramatic increase in the number of clinical trials focused on senescence and age-related disorders with interventions arising from geroscience. Second, we are lagging behind in care of older persons and geriatric medicine continues to suffer severe workforce inadequacies, especially for those with low or middle income. Societies must recognize the need and develop incentives, including financial, to bolster all facets of the eldercare workforce including public health, acute care and long-term care. Third, we have largely viewed aging as an accumulation of deficits and have systematically neglected the valuable capabilities that older people bring to society.
Oskar Hansson: In the space of neurodegenerative diseases, I think we are now moving into the therapeutic era, and I hope that the research community will develop several effective and safe interventions for these devastating brain diseases. Personally, I have especially high hopes for different genetic medicine approaches.
Anne Brunet: The field is moving forward very rapidly, and it is amazing to be part of it! I think there will be several translational breakthroughs in the next 5 to 10 years, notably for devastating age-related diseases such as Alzheimer's disease. Research-wise, it will be very cool to see what happens because so much more is feasible at the organismal level, and it will be an era of quantitative physiology that can be done at scale.
Ming Xu: In the next 5 to 10 years, I expect that the field of aging research will make incredible progress in these three directions. (1) I expect to see a significant rise in large-scale, human clinical trials for geroscience interventions. (2) Single-cell and spatial omics technologies will allow us to reveal the cellular and tissue-specific heterogeneity of aging. 3) AI will become an indispensable tool for aging research. AI and machine-learning models will be used to understand the complexity of multiomics data, identify novel aging targets and design personalized therapies.
Eiji Hara: Cellular senescence research is currently attracting considerable attention, with growing evidence that senescent cells are deeply involved in aging and various age-related diseases. Many studies suggest that targeting senescent cells could help to prevent or treat age-related conditions. Over the next 5-10 years, I expect we will gain a clearer understanding of several critical questions: which types of senescent cells drive specific pathologies, what are the optimal strategies for selective elimination versus functional modulation of these cells, and what are the potential risks of senolytic interventions.
Jing-Dong J. Han: I envision the next decade as the era when aging research becomes a predictive science. Big data will provide the 'language' of aging - a comprehensive, high-resolution dictionary of biological changes. AI models will be the 'translator', enabling us to read this language to forecast health trajectories, identify vulnerabilities and design personalized interventions long before clinical symptoms appear. The goal will be to move from treating age-related diseases to preemptively managing the aging process itself.
Felipe Sierra: As with all other areas of human activity, the field will be dominated by AI and other computer-based approaches to translate the biology of aging into interventions. In addition, I believe the field will succeed within the next 5 years at identifying predictive and clinically useful biomarkers that will take us into a more quantitative stage of research. I fear that, combined, AI and biomarkers will 'suck up the oxygen' from more basic mechanistic research, and this in turn will lead to progressively diminishing returns from AI and biomarkers.
Matt Kaeberlein: I am optimistic that the importance of geroscience will continue to gain recognition, and lead to greater investment from both public and private sectors. I expect substantial engagement from major pharmaceutical companies and anticipate the first FDA approval for a drug that slows aging, probably in companion animals. That milestone would mark a turning point for translational geroscience. Clinically, the landscape will remain frothy for a while. Some longevity clinics already practice evidence-based medicine, whereas others promote unproven or even unsafe interventions. Over time, I expect consolidation around data-driven, ethical standards.
View the full article at FightAging
Increasing Senolytic Effectiveness by Stressing Mitochondria 05 February 2026 - 05:09 PM
Researchers publishing in Nature Aging have described how mitochondrial stress is a key part of why senolytics are effective.
Finding targeted effectiveness
The researchers began this study by summarizing senescent cells and the senolytics created to eliminate them. They noted that few attempts have been made to determine which senolytics are the most broadly effective against senescent cells while having the least effects on non-senescent ones [1].
To that end, they created a senolytic specificity index (SSI), a simple metric that compares the number of senescent cells removed to the number of non-senescent cells removed. They tested 21 distinct agents, ranging from the well-known combination of dasatinib and quercetin (D+Q) to three different ABT compounds, one of which, ABT263 (Navitoclax), is well-known in the field as being an effective senolytic.
This researchers’ initial experiment confirmed that finding. Navitoclax was the most effective at selectively removing RPE-1 cells, which are human epithelial cells that are commonly used in senescence research; it was barely edged out in effectiveness by ARV825 at dealing with IMR-90, a line of human fibroblasts that serve the same purpose. Unfortunately, D+Q and fisetin performed very poorly on the SSI metric compared to these two compounds. Testing other types of senescent cells, and driving them senescent both replicatively and through toxin exposure, confirmed the broad effectiveness of both navitoclax and ARV825.
Some cells refuse to die
While these and similar compounds have advantages over other senolytics, such as not prompting suicidal apoptotic responses in non-senescent cells, they are not perfect. The researchers noted that previous work has found that BCL-2 inhibitors such as navitoclax are not effective against senescent preadipocytes [2] and that their own work has found imperfect clearance; roughly a quarter of the treated senescent cells survived navitoclax or ARV825, even after a week of senolytic treatment.
The researchers then took a step further, looking into why such strong senolytics failed against those particular cells. They found that the survivors had unusually high expressions of senescent cells’ characteristic SASP factors and that they fought more strongly against oxidative stress, decreasing the reactive oxygen species (ROS) that may have contributed to the other cells’ death.
Further analysis found that these cells were also better at clearing damaged mitochondria. One particular gene, ATP6V0E1, plays a key role in this process [3], and knocking this gene down greatly increased the effectiveness of navitoclax. The accumulation of damaged mitochondria is key to the effectiveness of both navitoclax and ARV825; cells with depleted mitochondria were significantly less likely to die to these senolytics.
Mitochondrial stress helps senolytics do their job
The researchers then experimented with various methods of imposing mitochondrial stress. First, they did so directly through gene silencing, finding that direct downregulation of mitochondrial maintenance functions causes senescent cells to die in the same way as when they are treated with these two senolytics. Directly interfering with mitochondrial DNA replication boosted their effects as well, and, critically, did not appear to kill off non-senescent cells.
The researchers switched cells from glycolysis to oxidative phosphorylation (OXPHOS) by reducing the amount of glucose that the cells received, simulating a low-carbohydrate diet and causing oxidative stress [4], but this had effects on normal cells as well as senescent ones. They then tested a GLUT1 inhibitor, BAY-876 [5], to force this shift; co-treating cells with BAY-876 along with navitoclax or ARV825 was found to increase the effectiveness of these senolytics while still sparing non-senescent cells from death.
These findings were replicated in mice. Older male mice were injected with melanoma cells that are known to co-locate with senescent cells, which fuel the growth of this cancer. Then, they were fed either navitoclax or ARV825 alongside either a normal or a low-carbohydrate ketogenic diet. The mice receiving the ketogenic diet had significantly stronger responses to senolytics; two key SASP factors that are known to attract this cancer were substantially reduced in the low-carb groups compared to the normal ones. While some previous work has linked ketogenic diets to cellular senescence [6], these researchers did not observe this in the lungs of their tested mice.
These findings are limited, and they present a conundrum to the field. The same basic stresses that prime senescent cells for removal by senolytics also affect how normal cells function. While these experiments showed benefits when stresses were combined with senolytics, it is still uncertain whether senolytics should be combined with physical interventions, such as low-carb diets or intensive exercise, for maximum effectiveness. Further work will need to be done on animals and people in order to determine if such combinations are helpful or harmful in the long run.
Literature
[1] Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021). Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nature reviews Molecular cell biology, 22(2), 75-95.
[2] Zhu, Y. I., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., … & Kirkland, J. L. (2016). Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors. Aging cell, 15(3), 428-435.
[3] Colacurcio, D. J., & Nixon, R. A. (2016). Disorders of lysosomal acidification—The emerging role of v-ATPase in aging and neurodegenerative disease. Ageing research reviews, 32, 75-88.
[4] Liu, Y., Song, X. D., Liu, W., Zhang, T. Y., & Zuo, J. (2003). Glucose deprivation induces mitochondrial dysfunction and oxidative stress in PC12 cell line. Journal of cellular and molecular medicine, 7(1), 49-56.
[5] Siebeneicher, H., Cleve, A., Rehwinkel, H., Neuhaus, R., Heisler, I., Müller, T., … & Buchmann, B. (2016). Identification and optimization of the first highly selective GLUT1 inhibitor BAY‐876. ChemMedChem, 11(20), 2261-2271.
[6] Wei, S. J., Schell, J. R., Chocron, E. S., Varmazyad, M., Xu, G., Chen, W. H., … & Gius, D. (2024). Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Science advances, 10(20), eado1463.
View the article at lifespan.io
Sex Differences in Atherosclerotic Cardiovascular Disease 05 February 2026 - 11:22 AM
The development of atherosclerosis is very different in males versus females. In the commonly used mouse models that develop atherosclerotic plaque in response to a high fat diet this is very evident. Interestingly, ovariectomized female mice develop plaque in a very similar way to male mice, indicating the importance of hormones to the mechanisms of atherosclerosis. In humans, atherosclerosis is broadly a male condition up to the age of menopause, at which point women start to catch up to the male extent of atherosclerotic plaque and subsequent cardiovascular disease and mortality.
Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States, though the age of onset differs by sex. Historical estimates suggest men experience earlier onset of coronary heart disease (CHD) by about 10 years as compared with women. Sex-specific differences in CVD are attributed to multiple different pathways, including hormonal influences, differences in cardiovascular health behaviors and factors, and exposure to adverse social determinants of health. Historically, men had higher rates of smoking, diabetes, and hypertension. However, population shifts in cardiometabolic risk phenotypes have resulted in similar or higher rates of obesity, diabetes, and hypertension in women than men. Additionally, the overall prevalence of smoking has decreased and is similar among men and women.
This study analysed data from the CARDIA (Coronary Artery Risk Development in Young Adults) study, a prospective multicenter cohort study. US adults aged 18 to 30 years enrolled in 1985 to 1986 and were followed through August 2020. Sex differences in the cumulative incidence functions of premature CVD (onset earlier than 65 years), were compared overall and for each subtype (CHD, heart failure, stroke).
Among 5,112 participants with a mean age of 24.8 ± 3.7 years at enrollment and a median follow-up of 34.1 years, men had a significantly higher cumulative incidence of CVD, CHD, and heart failure, with no difference in stroke. Men reached 5% incidence of CVD 7.0 years earlier than women (50.5 versus 57.5 years). CHD was the most frequent CVD subtype, and men reached 2% incidence 10.1 years earlier than women. Men and women reached 2% stroke and 1% heart failure incidence at similar ages. Sex differences in CVD risk emerged at age 35, persisted through midlife, and were not attenuated by accounting for cardiovascular health.
Link: https://doi.org/10.1161/JAHA.125.044922
View the full article at FightAging
α-Ketoglutarate Interacts with TET to Regulate Cellular Senescence 05 February 2026 - 11:11 AM
A recent human trial of α-ketoglutarate supplementation failed to show benefits, but researchers continue to show interest in α-ketoglutarate based on results in cells and animal studies. In this example, researchers link α-ketoglutarate availability to the regulation of cellular senescence via TET. It may be that this interaction is not as important to cellular senescence in humans as it is in mice, or that middle aged people (40 to 60) don't have a large enough burden of senescent cells to make effect sizes resulting from α-ketoglutarate supplementation easily visible, or that the optimal dose is higher than the trial dose. Regardless, it seems a poor substitute for senolytics if the goal is to influence the burden of senescence in older people.
Cellular senescence, a state of stable cell-cycle arrest associated with aging, is characterized by a distinct pro-inflammatory secretome. This study systematically interrogates the critical role of the α-ketoglutarate (AKG)-Ten-eleven translocation (TET) axis in regulating senescence in human somatic cells. Downregulating TET expression and activity, either genetically (siRNA) or pharmacologically (via C35), or limiting AKG bioavailability through a targeting peptide, trigger widespread epigenetic reprogramming, amplify pro-inflammatory signaling, and enhance the senescence-associated secretory phenotype (SASP), ultimately driving cells toward replicative senescence.
Conversely, augmenting AKG bioavailability or TET expression and activity significantly enhances cellular resilience to stress, effectively preventing and reversing senescent phenotypes. These findings not only position the AKG-TET axis as a critical regulatory nexus of cellular senescence but also challenge the traditional view of senescence as a fixed endpoint, revealing its dynamic and plastic nature susceptible to therapeutic intervention.
Link: https://doi.org/10.1016/j.isci.2025.114298
View the full article at FightAging
