Nav: Home

Peptide targeting senescent cells restores stamina, fur, and kidney function in old mice

March 23, 2017

Regular infusions of a peptide that can selectively seek out and destroy broken-down cells that hamper proper tissue renewal, called senescent cells, showed evidence of improving healthspan in naturally-aged mice and mice genetically engineered to rapidly age. The proof-of-concept study, published March 23 in Cell, found that an anti-senescent cell therapy could reverse age-related loss of fur, poor kidney function, and frailty. It is currently being tested whether the approach also extends lifespan, and human safety studies are being planned.

The peptide took over four years of trial and error to develop and builds on nearly a decade of research investigating vulnerabilities in senescent cells as a therapeutic option to combat some aspects of aging (Trends in Molecular Medicine, 10.1016/j.molmed.2016.11.006). It works by blocking the ability of a protein implicated in senescence, FOXO4, to tell another protein, p53, not to cause the cell to self-destruct. By interfering with the FOXO4-p53 crosstalk, the peptide causes senescent cells to go through apoptosis, or cell suicide.

"Only in senescent cells does this peptide cause cell death," says senior author Peter de Keizer, a researcher of aging at Erasmus University Medical Center in the Netherlands. "We treated mice for over 10 months, giving them infusions of the peptide three times a week, and we didn't see any obvious side effects. FOXO4 is barely expressed in non-senescent cells, so that makes the peptide interesting as the FOXO4-p53 interaction is especially relevant to senescent cells, but not normal cells."

Results appeared at different times over the course of treatment. Fast-aging mice with patches of missing fur began to recover their coats after 10 days. After about three weeks, fitness benefits began to show, with older mice running double the distance of their counterparts who did not receive the peptide. A month after treatment, aged mice showed an increase in markers indicating healthy kidney function.

Senescent cell therapy is one of several strategies being tested in mice aimed at reversing aging or lengthening healthspan. In 2015, the Valter Longo laboratory at the University of Southern California reported that mice on a calorie-restricted diet that mimics fasting benefited from a longer life, a reduction in inflammatory disease, and improved memory (Cell Metabolism, 10.1016/j.cmet.2015.05.012). And last December, Juan Carlos Izpisua Belmonte at the Salk Institute of Biological Science and colleagues made headlines with their discovery that cellular reprogramming of epigenetic marks could extend lifespan and improve health in fast-aging mice (Cell, 10.1016/j.cell.2016.11.052).

"This wave of research on how we can fight aging is complementary, and not in competition," says de Keizer. "The common thread I see for the future of anti-aging research is that there are three fronts in which we can improve: The prevention of cellular damage and senescence, safe therapeutic removal of senescent cells, to stimulate stem cells--no matter the strategy--to improve tissue regeneration once senescence is removed."

de Keizer aims to start a company based on these findings, but in the short term, he and his group want to show that their peptide is non-toxic in humans with no unforeseen side effects. They plan to offer a safety clinical trial in people with Glioblastoma multiforme, an aggressive brain tumor, which also shows high levels of the biomarkers needed for this FOXO4 peptide to be effective.
-end-
The work was supported by grants from the National Institutes of Health, the National Institute on Aging, the Austrian Science Fund, the Royal Netherlands Academy of Arts and Sciences, the Erasmus University Medical Center, the Dutch Kidney Foundation, and the Dutch Cancer Society. Co-author Judith Campisi is co-founder and shareholder of Unity Pharmaceuticals. Co-author Jan Hoeijmakers is co-founder of AgenD. Neither companies have been involved in this research.

Cell, Baar et al.: "Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging" http://www.cell.com/cell/fulltext/S0092-8674(17)30246-5

Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit http://www.cell.com/cell. To receive Cell Press media alerts, contact press@cell.com.

Cell Press

Related Aging Articles:

Brain development and aging
The brain is a complex organ -- a network of nerve cells, or neurons, producing thought, memory, action, and feeling.
Aging gracefully in the rainforest
In an article that appears in the current issue of Evolutionary Anthropology, researchers synthesize over 15 years of theoretical and empirical findings from long-term study of the Tsimane forager-farmers.
Reversing aging now possible!
DGIST's research team identified the mechanism of reversible recovery of aging cells by inducing lysosomal activation.
Brain-aging gene discovered
Researchers at Columbia University Medical Center have discovered a common genetic variant that greatly affects normal brain aging in older adults.
Aging can be good for you (if you're a yeast)
It's a cheering thought for anyone heading towards their golden years.
How eating less can slow the aging process
New research shows why calorie restriction made mice live longer and healthier lives.
Turning back the aging clock
By boosting genes that destroy defective mitochondrial DNA, researchers can slow down and potentially reverse an important part of the aging process.
Insilico Medicine launches a deep learned biomarker of aging, Aging.AI 2.0 for testing
Insilico Medicine, Inc., a company applying latest advances in deep learning to biomarker development, drug discovery and aging research, launched Aging.AI 2.0.
Substance with the potential to postpone aging
The coenzyme NAD+ plays a main role in aging processes.
What does a healthy aging cat look like?
Just as improved diet and medical care have resulted in increased life expectancy in humans, advances in nutrition and veterinary care have increased the life span of pet cats.

Related Aging Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Digital Manipulation
Technology has reshaped our lives in amazing ways. But at what cost? This hour, TED speakers reveal how what we see, read, believe — even how we vote — can be manipulated by the technology we use. Guests include journalist Carole Cadwalladr, consumer advocate Finn Myrstad, writer and marketing professor Scott Galloway, behavioral designer Nir Eyal, and computer graphics researcher Doug Roble.
Now Playing: Science for the People

#529 Do You Really Want to Find Out Who's Your Daddy?
At least some of you by now have probably spit into a tube and mailed it off to find out who your closest relatives are, where you might be from, and what terrible diseases might await you. But what exactly did you find out? And what did you give away? In this live panel at Awesome Con we bring in science writer Tina Saey to talk about all her DNA testing, and bioethicist Debra Mathews, to determine whether Tina should have done it at all. Related links: What FamilyTreeDNA sharing genetic data with police means for you Crime solvers embraced...