Scientists Are Trying to Define What ‘Reversing Aging’ Really Means

Imagine being 50 and watching your biological age fall to 45. Five years younger, according to your test.

Now imagine that result arriving alongside stronger muscles, easier movement, and a sharper memory. That would make quite a birthday present.

Connecting those two things – a younger test result and a body that works better – is a challenge that aging researchers are trying to solve. With treatments targeting aging entering human studies, deciding what counts as success is becoming increasingly practical.

In a Cell Metabolism commentary, researchers including Harvard Medical School’s Jesse Poganik and Vadim Gladyshev explore how to recognize convincing biological age reversal.

Their proposal brings together measurements of changes inside the body and assessments of what it can do. They also want to know whether improvements last beyond the treatment.

For anyone hoping to celebrate a younger result, that raises an intriguing question: what exactly has the test measured?

Your birth date gives your chronological age. Tests estimating biological age examine features of your body that change as people grow older.

Poganik explained to ScienceAlert that, for a well-validated molecular measure, a falling score means the features being measured have shifted toward patterns associated with younger people.

“It may be accurate to say ‘biological age assessed by this biomarker was reversed by the equivalent of five years’,” he told ScienceAlert.

A broader assessment would make that conclusion more convincing. But saying aging itself has been reversed goes further.

“Aging as a process is unidirectional and cannot be fully reversed, like time,” Poganik said.

The distinction is simple: traveling more slowly along a road does not mean you have gone back down it. Slower aging and becoming younger are different outcomes.

There is also a gap between studying groups and interpreting your own report. These tools are developed and validated in populations; their usefulness for individual people is still being established.

“So while they are excellent research tools, we have a way to go before we can be confident that they are useful when applied to individuals,” he said.

Even in a controlled trial, the results can depend on which aging measure researchers choose.

In CALERIE, adults were randomly assigned to reduce their calorie intake or continue eating as usual for two years. A 2023 analysis of blood samples found a small slowing in the estimated pace of aging using a tool called DunedinPACE.

Two other measures, PhenoAge and GrimAge, found no significant treatment-related change in estimated biological age.

Yet Poganik finds these large trials exciting. Measuring health outcomes alongside aging markers gives researchers a chance to investigate what a changing score actually means.

That brings the story back to muscles, memory, and everyday abilities.

Consider someone whose molecular measurements suggest an older biological age, but whose grip strength, hearing, and mobility remain intact. Researchers who prioritize function would question whether that person should count as biologically older.

Researchers favoring molecular measurements see another opportunity: detecting changes before those abilities decline, when there may be more time to intervene.

Both approaches have limits. Training can improve a particular physical skill without necessarily changing underlying aging processes. Molecular tests, meanwhile, do not consistently reflect the changes researchers might expect from exercise.

For now, the authors advocate measuring both.

The commentary points to XPRIZE Healthspan as one concrete example of assessing rejuvenation through muscle, cognitive, and immune function. Poganik also names the competition among the initiatives whose future findings excite him.

A convincing result will also need to survive repeat testing. Poganik outlines three practical checks.

“Was the same measurement used before and after the intervention? Did the change persist after the intervention ended? And was it reproduced using an orthogonal approach?”

This could help distinguish lasting change from misleading fluctuations. An unusually high first reading, for example, may be followed by a result closer to someone’s usual level without any rejuvenation occurring.

The paper identifies this statistical effect, called regression to the mean, among the explanations researchers should rule out.

Related: A New Biological Clock Could Predict When You’ll Probably Die

The hope is that different measurements will begin to tell a consistent story: Younger molecular patterns accompanied by lasting improvements in how the body functions.

So imagine that biological age report saying ’45’ again. Alongside it, picture evidence that you can move more easily, think more clearly, and sustain those gains.

That would give you much more than a number to celebrate.

The commentary was published in Cell Metabolism.