LOS ANGELES— A new study led by researchers at the University of Southern California (USC) Leonard Davis School of Gerontology has demonstrated that humanin, a peptide encoded in the small genome of mitochondria, has a huge impact on longevity and healthier lives in both animals and humans. Perhaps the most compelling finding is that humanin could be a key factor to lowering risk for diseases such as Alzheimer’s disease (AD).
Dementia, of which Alzheimer’s is the most common form, is affects an estimated 36 million people worldwide, according to the National Institutes of Health (NIH). This number is expected to rise to 115 million by 2050 unless an effective therapeutic is developed.
“Humanin has long been known to help prevent many age-related diseases, and this is the first time that it has been shown that it can also increase lifespan,” says senior author Dr. Pinchas Cohen, a professor of gerontology, medicine and biological sciences and dean of the Leonard Davis School of Gerontology.
“While there have been many studies examining the effects of humanin in preventing AD in animal models, it was our observations that humanin declines with age in several species—combined with the fact that humanin treatment can prevent many age-related diseases—that gave us the idea that humanin would be involved in the general aging process,” Cohen tells DDN.
“The biggest takeaway would be that humanin can both increase healthspan and lifespan of model organisms, and this study suggests that it could be a novel anti-aging peptide for humans,” he adds. “The anti-AD properties of humanin have been known for a while, and this recent study combined with our previous studies extends the known beneficial effects of humanin to lifespan and healthspan extension.”
Kelvin Yen, a research assistant professor at USC Leonard Davis School of Gerontology and first author of the paper, comments, “This study has been a culmination of nearly a decade worth of data that we have been slowly accumulating. The in-vivo studies are more recent having been performed in the past few years. The next steps are to determine how humanin achieves all these beneficial effects ... to humans.”
Humanin has been found in the animal kingdom throughout evolution, according to the study, which was published online in the journal Aging. Researchers examined humanin in worms, mice and humans, including Alzheimer’s patients and the children of centenarians.
“The results highlight the potential for humanin and other mitochondrial proteins to become treatments for age-related ailments and indicate that humanin may be an ancient mitochondrial signaling mechanism that is key for regulating the body’s health and lifespan,” states Yen.
At the same time, he notes that humanin levels have previously been observed to decrease with age in many species. In this new study, the scientists observed higher levels of humanin in organisms predisposed to long lives, including the age-resistant naked mole rat, which experiences only a very slow decline in levels of humanin circulating in the body throughout its 30-year lifespan.
“In contrast, mice experience a 40-percent drop in humanin over the first 18 months of life, and primates such as rhesus macaques appeared to have a similarly dramatic drop in humanin between the ages of 19 and 25,” Yen points out.
In humans, researchers observed higher and more sustained levels of humanin in 18 children of centenarians versus a control group of 19 children of non-centenarians, according to Yen. Individuals whose parents reach 100 years old are statistically more likely than other people to reach very old age.
The study reports that in some species, including worms and mice, modifying their genes to produce higher amounts of humanin within their bodies was enough to significantly increase lifespans, but these longer-lived animals had fewer offspring. Scientists have observed a similar pattern in long-lived humans.
“This tradeoff between longevity and reproduction is thought to be due to an evolutionarily conserved balance between using energy to produce more offspring, or using the energy to maintain the organism for future reproductive efforts,” Yen explains. “Evolutionarily speaking, the goal of life is to reproduce and then you’re done. But if you can’t reproduce, you should try to hang around as long as possible—and a side effect of that is longevity.”
Researchers also analyzed samples of cerebral spinal fluid from a small number of Alzheimer’s patients and control individuals without dementia, and noticed that humanin levels were much lower in the Alzheimer’s patients. In newborn cord blood samples, high levels of humanin correlated with a high mitochondrial DNA copy number, or the number of copies of the mitochondrial genome present within each cell.
“Humanin levels are inversely correlated with a decrease in mitochondrial DNA copy number, which in itself has been associated with a number of different diseases such as cancer, kidney disease and cardiovascular disease,” says Yen.
“This study, as well as many others, suggests that humanin administration would be an effective therapeutic treatment for a large number of diseases, and further solidifies the importance of the mitochondria beyond its traditional role as the ‘powerhouse of the cell,’” Cohen concludes.
While the bulk of the work was performed by Cohen and Yen at USC, this research was a multi-university effort by more than 20 authors at eight universities and was supported by multiple funding sources.