Scientists Find Longevity Gene That Helps Mice Live Longer

Key Takeaways

• Naked mole rats live far longer than similar‑sized rodents and stay remarkably healthy as they age; one factor is their unusually high levels of a protective molecule called high‑molecular‑weight hyaluronic acid (HMW‑HA).

• Researchers engineered mice to carry the naked mole rat version of the hyaluronan synthase 2 gene, boosting HMW‑HA production. These mice showed better overall health, lower age‑related damage, and about a 4.4% increase in median lifespan compared with typical mice.

• The study is an early proof of concept that longevity adaptations in one mammal can be transferred to another, pointing to future strategies that enhance HMW‑HA pathways to support healthy aging.

Naked mole rats are small rodents that can live for more than four decades—nearly ten times longer than many animals of similar size. As they age, they maintain an unusual level of resilience: they tend to keep physical function, tissue integrity, and cellular health far longer than expected.

One major clue is their abundance of HMW‑HA, a form of hyaluronic acid that is larger and more structurally protective than what is typically found in humans or mice. Naked mole rats carry roughly ten times more of this molecule. Earlier work showed that when HMW‑HA was removed from their cells, those cells became more prone to uncontrolled growth and stress‑related damage, suggesting HMW‑HA acts as a kind of biochemical shield.

Transferring a Longevity Gene Into Mice

To see whether this shield could help another species, the University of Rochester team introduced the naked mole rat version of the hyaluronan synthase 2 (HAS2) gene into mice. All mammals have HAS2, but the naked mole rat variant is especially active and drives higher production of HMW‑HA.

The engineered mice developed elevated HMW‑HA levels in multiple tissues. Over time, they showed:

• Less age‑related tissue damage

• Better preservation of gut health and tissue structure

• Lower levels of chronic, background inflammation

• A 4.4% increase in median lifespan relative to unmodified mice

Because persistent, low‑grade inflammation is a hallmark of biological aging, the reduction in inflammatory signals is particularly important. The findings suggest HMW‑HA may influence not only structural support around cells but also how the immune system responds as the body grows older.

What This Means for Human Healthy Aging

On its own, a roughly 4% lifespan gain in mice is modest. The deeper importance lies in what the experiment demonstrates: a protective aging mechanism that evolved in a long‑lived mammal can be exported into another mammal and still work.

For human longevity research, the authors highlight two main avenues:

• Slowing the breakdown of HMW‑HA, allowing naturally produced molecules to persist longer in tissues

• Boosting its production, for example by targeting human versions of the HAS enzymes or pathways that regulate them

Early candidate compounds that slow hyaluronan degradation are already being explored in preclinical models.

Since this work, additional studies have uncovered other protective features in naked mole rats—such as versions of DNA‑maintenance proteins that appear to enhance genomic stability and delay cellular aging. Taken together, these findings point to a broader pattern: long‑lived species likely stack multiple overlapping defenses—better control of inflammation, stronger genome maintenance, and tissue‑protective molecules like HMW‑HA—rather than relying on a single “magic switch.”

The naked mole rat gene‑transfer study stands out as a striking early example. A survival strategy from one of nature’s longest‑lived small mammals helped mice stay healthier and live longer. The next challenge is determining whether similar biological levers can be safely adapted to support human healthspan, while staying within regulatory guidelines that focus on promoting healthy aging rather than treating or preventing specific conditions.

References:

1. Zhihui Zhang, Xiao Tian, J. Yuyang Lu, Kathryn Boit, Julia Ablaeva, Frances Tolibzoda Zakusilo, Stephan Emmrich, Denis Firsanov, Elena Rydkina, Seyed Ali Biashad, Quan Lu, Alexander Tyshkovskiy, Vadim N. Gladyshev, Steve Horvath, Andrei Seluanov, Vera Gorbunova. Increased hyaluronan by naked mole-rat Has2 improves healthspan in mice. Nature; 621 (7977): 196 DOI: 10.1038/s41586-023-06463-0