Usc Leonard Davis School of Gerontology

Patients with growth hormone receptor deficiency, or Laron syndrome, appear to have lower than average risk factors for cardiovascular disease, according to a new study. A new study highlights possible cardiovascular health advantages in individuals with a rare condition known as growth hormone receptor deficiency (GHRD), also called Laron syndrome. GHRD, which is characterized by the body's impaired ability to use its own growth hormone and results in stunted growth, has been linked in mice to a record 40% longevity extension and lower risks for various age-related diseases. However, the risk of cardiovascular disease in individuals with GHRD has remained unclear until now, leading to the speculation that in people, this mouse longevity mutation may actually increase cardiovascular disease. The study, appearing in Med on April 26, 2024, is the latest product of an international collaboration spanning nearly 20 years between Valter Longo, professor of gerontology at the USC Leonard Davis School of Gerontology, and endocrinologist Jaime Guevara-Aguirre of the Universidad San Francisco de Quito, Ecuador. Over the past two decades, Longo, Guevara-Aguirre and colleagues have examined the health and aging of people with the gene mutation that causes GHRD. This rare mutation -- found in just 400 to 500 people worldwide -- was identified in a group of Ecuadorians whose ancestors had fled Spain during the Inquisition more than three centuries ago. The mutation leaves them with ineffective growth hormone receptors and results in a type of dwarfism. The team's previous research has indicated that while GHRD/Laron syndrome reduces growth, it also appears to reduce the risk of several age-related diseases. Although the Ecuadorians with GHRD have a higher rate of obesity, they have a very low risk of cancer and Type 2 diabetes. They also appear to have healthier brains and better performance on tests of cognition and memory. For the current study, the research team examined cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. Researchers conducted two phases of measurements in Los Angeles and Ecuador, involving a total of 51 individuals, with 24 diagnosed with GHRD and 27 relatives without GHRD serving as controls. Key findings from the study included: "These findings suggest that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors compared to their relatives," said Longo, senior author of the new study. "Although the population tested is small, together with studies in mice and other organisms this human data provide valuable insights into the health effects of growth hormone receptor deficiency and suggest that drugs or dietary interventions that cause similar effects could reduce disease incidence and possibly extend longevity." Along with co-corresponding authors Longo and Guevara-Aguirre, the study's coauthors included Amrendra Mishra and Priya Balasubramanian of USC; Carolina Guevara, Álvaro Villacres, Gabriela Peña, and Daniela Lescano of the Universidad San Francisco de Quito; Alexandra Guevara of the Instituto de Endocrinologia Metabolismo y Reproducción (IEMYR) in Quito; Marco Canepa of the University of Genova, Italy; and John Kopchick of Ohio University. Funding including National Institutes of Health/National Institute on Aging grant P01 AG034906 to Longo.

Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new study. Cycles of a diet that mimics fasting can reduce signs of immune system aging, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new USC Leonard Davis School of Gerontology-led study. The study, which appears in Nature Communications on Feb. 20, adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD). The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast. The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study. "This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age," Longo said. Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects. They can: In addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans. The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now. Lower disease risks & more youthful cells The study analyzed the diet's effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients who were randomized to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days. The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids. Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet. An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results. Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome. In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio -- an indicator of a more youthful immune system. Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age -- a measure of how well one's cells and tissues are functioning, as opposed to chronological age -- by 2.5 years on average. "This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function," Longo said. The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD's potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said. "Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age," Longo said.

Did the ancient Greeks and Romans experience Alzheimer's? Medical texts from 2,500 years ago rarely mention severe memory loss, suggesting today's widespread dementia stems from modern environments and lifestyles, a new analysis shows. You might think age-related dementia has been with us all along, stretching back to the ancient world. But a new analysis of classical Greek and Roman medical texts suggests that severe memory loss -- occurring at epidemic levels today -- was extremely rare 2,000 to 2,500 years ago, in the time of Aristotle, Galen and Pliny the Elder. The USC-led research, published in the Journal of Alzheimer's Disease, bolsters the idea that Alzheimer's disease and related dementias are diseases of modern environments and lifestyles, with sedentary behavior and exposure to air pollution largely to blame. "The ancient Greeks had very, very few -- but we found them -- mentions of something that would be like mild cognitive impairment," said first author Caleb Finch, a University Professor at the USC Leonard Davis School of Gerontology. "When we got to the Romans, and we uncovered at least four statements that suggest rare cases of advanced dementia -- we can't tell if it's Alzheimer's. So, there was a progression going from the ancient Greeks to the Romans." Ancient Greeks recognized that aging commonly brought memory issues we would recognize as mild cognitive impairment, or MCI, but nothing approaching a major loss of memory, speech and reasoning as caused by Alzheimer's and other types of dementia. Finch and co-author Stanley Burstein, a historian at California State University, Los Angeles, pored over a major body of ancient medical writing by Hippocrates and his followers. The text catalogs ailments of the elderly such as deafness, dizziness and digestive disorders -- but makes no mention of memory loss. Centuries later in ancient Rome, a few mentions crop up. Galen remarks that at the age of 80, some elderly begin to have difficulty learning new things. Pliny the Elder notes that the senator and famous orator Valerius Messalla Corvinus forgot his own name. Cicero prudently observed that "elderly silliness … is characteristic of irresponsible old men, but not of all old men." Finch speculates that as Roman cities grew denser, pollution increased, driving up cases of cognitive decline. In addition, Roman aristocrats used lead cooking vessels, lead water pipes and even added lead acetate into their wine to sweeten it -- unwittingly poisoning themselves with the powerful neurotoxin. (A few ancient writers recognized the toxicity of lead-containing material, but little progress was made in dealing with the problem until well into the 20th century. Some scholars blame lead poisoning for the fall of the Roman Empire.) For this paper, Finch did not just think about the Roman Empire or the Greeks. In the absence of demographic data for ancient Greece and Rome, Finch turned to a surprising model for ancient aging: today's Tsimane Amerindians, an Indigenous people of the Bolivian Amazon. The Tsimane -- like the ancient Greeks and Romans -- have a preindustrial lifestyle that is very physically active, and they have extremely low rates of dementia. An international team of cognitive researchers led by Margaret Gatz, a professor of psychology, gerontology and preventive medicine at the USC Leonard Davis School, found among older Tsimane people, only about 1% suffer from dementia. In contrast, 11% of people aged 65 and older living in the United States have dementia, according to the Alzheimer's Association. "The Tsimane data, which is quite deep, is very valuable," Finch said. "This is the best-documented large population of older people that have minimal dementia, all of which indicates that the environment is a huge determinant on dementia risk. They give us a template for asking these questions." The paper was supported by funds from the Cure Alzheimer's Fund and the National Institutes of Health (P01 AG055367 and R01 AG05442).