As you age you naturally lose neurons and muscle mass and experience a decline in fertility and wound healing ability.

Previous research in animals has offered several potential techniques for turning back the biological clock in specific tissues, including exercise and calorie restriction.

However, age reversal of blood cells or at whole organism level has so far been elusive.

Longhua Guo, Ph.D., assistant professor of Molecular and Integrative Physiology and Cell and Developmental Biology at U-M Medical School, has been interested in planarians (Schmidtea mediterranea) as a model system for aging research because they are considered immortal, and can regenerate body parts, even so far as to grow new heads after being decapitated.

“People have been aware of planarians’ regenerative capacity for more than 100 years. But very little is known about how they regenerate and why they live seemingly forever,” said Guo, who is a member of the U-M Institute of Gerontology.

His lab is examining the aging process in sexually reproducing planarians in order to more readily define their age, starting from the zygote stage.

From fertilization to around 18 months, planarians, like mammals, show signs of decline, notes Guo, including the loss of neurons, muscle and diminished fertility.

One of their more obvious signs of age are abnormal changes in their eyes over time.

When the older planarians’ heads were removed, however, they generated new heads with normal eyes.

Further studies found that worms that had undergone regeneration also saw improved fertility as well as renewed physiological performance when compared to older planarians.

Their findings are described in the journal Nature Aging.

Additionally, unlike mammals, Guo’s team discovered that planarians did not lose adult stem cells with age and that regeneration reversed age-associated transcriptional changes in various tissues.

“In the older planarians, not only did they not lose the regenerative capacity, but they can also still completely regenerate, which is different from a lot of species already, suggesting they have mechanisms to support longevity and healing even at much older ages,” he said.

The team also directly compared single cell sequencing data from planarians with datasets of mouse, rat, and human aging and mice that have undergone lifespan-extending interventions.

They found that signatures of aging from planarians are shared with aging mammals and, more interestingly, with those of lifespan extended mice.

Guo’s next goal is to define the genes and cells of the regenerative program that lead to planarians’ reversal of aged states.

“The message of this study is that age-associated decline may be reversible at whole-organism level, not just for the planarians, but other organisms.”

Additional authors: Xiaoting Dai, Xinghua Li, Alexander Tyshkovskiy, Cassandra Zuckerman, Nan Cheng, Peter Lin, David Paris, Saad Qureshi, Leonid Kruglyak, Xiaoming Mao, Jayakrishnan Nandakumar, Vadim N. Gladyshev, Scott Pletcher and Jacob Sobota.

Funding/disclosures: Glenn Foundation for Medical Research, Global Consortium for Reproductive Longevity & Equality, AFAR, The Pew Charitable Trusts and the National Institute on Aging of the National Institutes of Health.

Paper cited: “Regeneration leads to global tissue rejuvenation in aging sexual planarians,” Nature Aging. DOI: 10.1038/s43587-025-00847-9

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