Scientists discover a two-stage aging process that may cause cancer and arthritis

 

Researchers are offering a new way to understand why aging is so closely connected to chronic illness. In a review published in Aging-US titled "Aging as a multifactorial disorder with two stages," scientists from University College London and Queen Mary University of London describe a model suggesting that diseases linked to aging may develop through two separate but connected phases over the course of life.

The review was written by David Gems and Alexander Carver from University College London, along with Yuan Zhao from Queen Mary University of London. Their work combines ideas from evolutionary biology with findings from modern biomedical research to explain how early damage in the body may later contribute to diseases such as cancer, arthritis, and infections.

How Early-Life Damage May Shape Health Decades Later

According to the researchers, the first stage begins earlier in life when the body experiences various forms of disruption. These can include infections, physical injuries, or genetic mutations. While the body is often able to repair or contain much of this damage, some of it may remain hidden rather than being fully removed.

The second stage occurs later in life as normal genetic activity starts changing in ways that are no longer beneficial to the body. These late-life biological changes can weaken the body's ability to keep earlier damage under control. As a result, previously contained problems may gradually develop into disease.

The scientists argue that this process helps explain why many illnesses appear mainly in older adults even though their origins may trace back much earlier.

Why Diseases Like Shingles and Arthritis Appear With Age

The review highlights aging as a multifactorial process, meaning it is driven by many interacting biological factors instead of a single cause. The proposed model suggests that the combination of earlier damage and later-life genetic changes plays a major role in age-related disease.

For example, dormant viruses that remain inactive for years can become active again when the immune system weakens with age, leading to conditions such as shingles. In a similar way, injuries sustained in youth may eventually contribute to osteoarthritis as aging tissues become less resilient over time.

Inherited genetic mutations may also stay silent for decades before increasing the risk of diseases such as cancer or fibrosis later in life.

Evolutionary Biology and Aging Research

The researchers say their model builds on long-standing evolutionary theories of aging. One influential idea is that natural selection becomes weaker later in life, allowing harmful biological processes to emerge with age because they have less impact on reproduction and survival earlier in life.

The review also references studies involving the roundworm Caenorhabditis elegans. In these experiments, early mechanical damage in the worms eventually led to fatal infections in old age. The scientists suggest similar patterns may also occur in humans.

A New Framework for Healthier Aging

Overall, the review presents aging as a process shaped by multiple interacting causes that unfold over time. By separating aging into two major stages, early-life damage and later-life genetic activity, the researchers believe their framework could help guide future strategies aimed at disease prevention and healthier aging.

The findings also raise the possibility that reducing damage earlier in life or targeting harmful late-life biological changes could help lower the risk of chronic disease in older adults.

Journal Reference:

1. David Gems, Alexander Carver, Yuan Zhao. Aging as a multifactorial disorder with two stages. Aging, 2025; 17 (12): 2989 DOI: 10.18632/aging.206339

Courtesy:

Impact Journals LLC. "Scientists discover a two-stage aging process that may cause cancer and arthritis." ScienceDaily. ScienceDaily, 21 May 2026. <www.sciencedaily.com/releases/2026/05/260521072420.htm>. 

 

 

 

Scientists successfully transfer longevity gene and extend lifespan

 

Naked mole rats are not much to look at, but their biology has made them one of the most fascinating animals in aging research. These small, wrinkled rodents can live for decades, rarely develop cancer, and seem unusually protected from many of the diseases that normally arrive with age.

Researchers at the University of Rochester showed that one of those biological advantages can be moved into another mammal. By transferring a gene linked to the naked mole rat's unusually high levels of high molecular weight hyaluronic acid (HMW-HA), the team improved health and modestly extended lifespan in mice.

The work, published in Nature in 2023, suggested that at least some longevity traits that evolved in long-lived animals may be adaptable beyond the species that developed them. The genetically modified mice lived healthier lives and had an approximate 4.4 percent increase in median lifespan compared with ordinary mice.

"Our study provides a proof of principle that unique longevity mechanisms that evolved in long-lived mammalian species can be exported to improve the lifespans of other mammals," says Vera Gorbunova, the Doris Johns Cherry Professor of biology and medicine at Rochester.

Gorbunova, along with Andrei Seluanov, a professor of biology, and their colleagues, focused on a gene that helps produce HMW-HA. This substance is abundant in naked mole rats and has been tied to their striking resistance to cancer, inflammation, and age-related decline.

Why Naked Mole Rats Fascinate Aging Scientists

Naked mole rats are about the size of mice, yet their lifespans are extraordinary for rodents. They can live up to 41 years, nearly ten times longer than similarly sized rodents.

Their long lives are not the only reason scientists study them. As they age, naked mole rats appear to avoid many conditions that commonly affect other mammals, including neurodegeneration, cardiovascular disease, arthritis, and cancer. For decades, Gorbunova, Seluanov, and other researchers have been investigating how these animals stay so resilient.

One major clue is HMW-HA. Naked mole rats carry roughly ten times more of it than mice and humans. In earlier work, researchers found that when HMW-HA was removed from naked mole rat cells, those cells became more likely to form tumors.

That finding raised a powerful question. If HMW-HA helps naked mole rats resist cancer and age-related damage, could the same mechanism work in a different animal?

Transferring a Naked Mole Rat Longevity Gene

To test the idea, the Rochester team engineered mice to carry the naked mole rat version of the hyaluronan synthase 2 gene. This gene helps make the protein that produces HMW-HA.

All mammals have a version of hyaluronan synthase 2, but the naked mole rat version appears to be especially active. It seems to drive stronger gene expression, leading to greater production of the protective molecule.

The modified mice developed higher levels of hyaluronan in several tissues. They also showed stronger protection against spontaneous tumors and chemically induced skin cancer.

The effects were not limited to cancer resistance. The mice carrying the naked mole rat gene stayed healthier overall, lived longer than regular mice, had less inflammation in multiple tissues as they aged, and maintained better gut health.

Because chronic inflammation is one of the major biological features of aging, the reduction in inflammation was especially important. The researchers believe HMW-HA may work partly by directly influencing the immune system, although more research is needed to explain exactly how it produces such broad benefits.

A Small Lifespan Gain With Big Implications

The increase in median lifespan was about 4.4 percent, which is modest. But the larger significance is that a longevity mechanism from one mammal was successfully transferred to another.

That makes the finding more than a mouse study about a single gene. It supports the idea that nature's long-lived species may contain biological tools that can be studied, adapted, and possibly used to improve health in other animals.

"It took us 10 years from the discovery of HMW-HA in the naked mole rat to showing that HMW-HA improves health in mice," Gorbunova says. "Our next goal is to transfer this benefit to humans."

The researchers believe there may be two main ways to pursue that goal. One would be to slow the breakdown of HMW-HA in the body. Another would be to increase its production.

"We already have identified molecules that slow down hyaluronan degradation and are testing them in pre-clinical trials," Seluanov says. "We hope that our findings will provide the first, but not the last, example of how longevity adaptations from a long-lived species can be adapted to benefit human longevity and health."

Newer Research Adds to the Naked Mole Rat Story

Since the 2023 Nature study, naked mole rats have continued to offer new clues about why they age so differently from other mammals. A 2025 study in Science reported another potential longevity mechanism involving cGAS, a protein better known for its role in immune defense. In humans and mice, cGAS can interfere with some forms of DNA repair, but the naked mole rat version appears to help cells repair DNA damage more effectively. That study found that specific changes in the naked mole rat protein improved genome stability and delayed signs of aging in experimental models.

This newer work does not replace the HMW-HA finding. Instead, it strengthens a broader pattern. Naked mole rats likely owe their unusually long, healthy lives to several overlapping defenses, including cancer resistance, inflammation control, DNA repair, and tissue protection.

For human aging research, that matters. A single molecule is unlikely to become a simple fountain of youth. But each discovery gives scientists another possible route for targeting the biological processes that drive age-related disease.

The 2023 gene transfer study remains a striking proof of concept. A survival strategy that evolved in one of nature's strangest mammals helped mice resist disease, age more smoothly, and live longer. The next challenge is determining whether those same biological tricks can be safely adapted to improve human healthspan.

Journal Reference:

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, 2023; 621 (7977): 196 DOI: 10.1038/s41586-023-06463-0

Courtesy:

University of Rochester. "Scientists successfully transfer longevity gene and extend lifespan." ScienceDaily. ScienceDaily, 10 May 2026. <www.sciencedaily.com/releases/2026/05/260510030948.htm>.