Twelve candidate indicators, based on studies in mice, could make developing anti-aging interventions faster—while offering new insights into age-related diseases.
Drugs, diets, and single-gene mutations can all slow aging in mice—but one of the biggest obstacles in research today is having to wait years, or even decades, to see whether a particular intervention works. A new article published today in Frontiers in Science argues that researchers may be able to use measurable biological signals called aging rate indicators (ARIs) to detect much sooner whether an intervention slows the pace of aging.
An ARI is a single measurement, taken at a single age, that indicates whether an intervention has shifted animals into a slow-aging state. By contrast, many familiar tests that estimate "biological age" gauge how much aging has already accumulated, and must be taken at least twice to show whether anything has changed.
This new ARI-based approach could accelerate the search for treatments that extend healthy years of life, while also sharpening scientists' understanding of the biological processes that connect aging to major chronic diseases—from diabetes and cancer to cardiac and neurodegenerative diseases.
Senior author Prof Richard A. Miller from the University of Michigan said: "We hope aging rate indicators (ARIs) will advance the search for anti-aging drugs in three ways. First, they may provide a quicker and less expensive way to select drugs that deserve testing in mice. Second, they may allow us to see which drugs can induce patterns of change in healthy people that make them more similar to slow aging mice, and therefore give clues about drugs that may slow aging in people. Lastly, the ARI panel can give us clues about the changes shared by many—perhaps all—anti-aging drugs, and in this way select way targets and new drug families to work on."
Evidence based interventions could extend healthy lifespan
The researchers reviewed evidence from mouse studies conducted under the US National Institute on Aging-supported Interventions Testing Program, which has identified 14 agents or combinations shown to significantly extend lifespan, with 8 producing increases of 12% or more [2]. Several were effective even when initiated in late adulthood.
The team found that many of the same molecular and physiological changes appeared whether the extended lifespan was caused by drugs, a calorie-restricted diet, and single-gene mutations.
These key changes, which distinguish control mice from slow-aging mice, provide the basis for the team's 12 proposed candidate ARIs [3]. A full mouse lifespan study takes 3–4 years. The authors estimate that if ARIs can reliably separate effective drugs from ineffective ones, mouse studies could be done around four times faster and at roughly one-twentieth the cost.
These candidate markers are not yet ready for clinical use, and the authors stress that they still need to be validated across mammalian species and tested in humans.
The researchers' focus is now testing the robustness of each ARI, finding additional ARIs that can be measured in blood plasma, uncovering how different interventions influence them, and clarifying their connections to late-life diseases. If confirmed, ARIs could offer a vital and practical bridge between basic aging biology and shorter, more feasible trials of interventions designed to promote healthier aging.
Lead author Prof Steven Austad from the University of Alabama at Birmingham said: "The surprising discovery in mice that many effective anti-aging drugs remain fully active even when started in late adulthood suggests that similar therapies could perhaps benefit people in middle age, which is an exciting possibility. ARIs could play a pivotal role in advancing these preventative therapies, culminating—eventually—in human clinical trials that can be completed in far shorter timeframes to speed access to new anti-aging drugs."
Co-author Dr Matt Kaeberlein added: "The biggest challenge in translating the biology of aging into better health is knowing whether an intervention actually affects the rate of aging. Developing and validating aging rate indicators could give us the tools to answer that question on a practical timescale, rather than waiting years or decades for lifespan outcomes. If we can do that rigorously, it will fundamentally change our ability to find interventions that extend healthy lifespan."
