Genetic variance is key to longevity; Migratory restlessness innate in resident birds
Researchers identify genetic variants that lend clues to living longer
Many studies show that tweaking a single gene can extend life span in animal models. In a new study published in the open access journal PLoS Biology, Drs. Gil Atzmon and Nir Barzilai at the Albert Einstein College of Medicine of Yeshiva University have found that people harbor alleles—alternative forms of a gene—that confer the same sort of longevity advantage.
The researchers looked for genetic clues to longevity in a group of 214 Ashkenazi Jews who have passed or nearly reached 100 years of age. In PLoS Biology, they report that a specific genetic profile, or genotype, was associated with longevity as well as cardiovascular health, lower incidence of hypertension and healthy insulin metabolism.
“Since centenarians typically escape cardiovascular disease, diabetes, and other age-related disorders, we suspected these most senior of senior citizens might possess gene variations that help them reach a ripe old age,” said Dr. Nir Barzilai, director of the Institute for Aging Research at Einstein and senior author on the paper. “If so, then these genotypes should occur with higher frequency in centenarians than in the rest of us.”
Dr. Barzilai and his colleagues recruited Ashkenazi Jews for the study, because this population--descended from a founder group of just 30,000 or so people—is more genetically uniform than other groups, simplifying the challenge of associating a genotype with its physical manifestation (phenotype).
When studying centenarians, finding an age-matched control group is obviously difficult. But since longevity runs in families, the researchers were able to get around this problem by recruiting children of the centenarians and matching them against a control group consisting of other Ashkenazi Jews the same age.
Each participant had blood drawn—to determine their genotype and to measure levels of several cardiovascular disease markers including insulin, cholesterol, triglycerides, high-density lipoproteins (HDL, the “good” cholesterol), low-density lipoproteins (LDL, the “bad” cholesterol), and concentrations of two lipoprotein components called apolipoproteins (APO). In a previous study, the researchers had found that centenarians’ LDL and HDL particle sizes are larger than normal, so these were also measured.
To identify genes associated with long life, they looked for single nucleotide polymorphisms (SNPs) in 36 genes involved in lipoprotein metabolism and other pathways linked to cardiovascular disease. (DNA contains four possible nucleotides—adenine, thymine, guanine and cytosine—and SNPs are variations of a single nucleotide in the DNA sequence.)
This analysis revealed a SNP in a gene with a clear pattern of age-dependent frequency: apolipoprotein C3 (APOC3). This polymorphism substitutes cytosine for adenine in the gene’s promoter region, where gene transcription is initiated. The frequency of finding the APOC3 polymorphism in both copies of the gene was 25% among centenarians, 20% in their offspring, and only 10% in controls.
APOC3 codes for a protein that is a major component of very low density lipoproteins (VLDL, another type of “bad” cholesterol) and also occurs in HDL. The researchers expected that people carrying the APOC3 SNP would have a favorable lipoprotein profile. And indeed, all participants carrying the APOC3 polymorphism had better triglyceride and cholesterol levels, as well as the beneficial larger LDL and HDL particle sizes. In addition, they had a much lower prevalence of hypertension.
Altogether, the statistical links between APOC3 and longevity and the significant associations between favorable lipoprotein-related traits and longevity strongly suggest that the genotype contributes in several ways to cardiovascular health and longevity.
While the genetic pathways driving longevity remain unknown, it seems clear that lipoprotein metabolism plays an important role. The favorable lipoprotein profiles reported by the Einstein researchers correlate with studies of Japanese and Italian centenarians as well. The Einstein researchers hope to uncover more clues regarding the genetic influences on aging—and begin to develop strategies to ease the inevitable slide into our twilight years.
Citation: Atzmon G, Rincon M, Schechter CB, Shuldiner AR, Lipton RB, et al. (2006) Lipoprotein genotype and conserved pathway for exceptional longevity in humans. PLoS
Biol 4(4): e113.
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Albert Einstein College of Medicine
*** Resident birds display migratory restlessness
Studies of migratory behavior have shown that captive migratory birds demonstrate a seasonally appropriate spontaneous urge to migrate, called Zugunruhe (pronounced zook-oon-roo-ha). This behavior varies with the species studied, with amount and direction of activity reflecting the species’ natural migratory distance and route, suggesting that the migratory urge is innate. In a new study published in the premier open access journal PLoS Biology, Barbara Helm and Eberhard Gwinner took a different approach and discovered that resident species who don’t migrate also exhibit this behavior.
Helm and Gwinner searched for signs of migratory behavior in two subspecies of stonechats, Saxicola torquata, comparing a migrant that breeds in Austria, S. t. rubicola, and its equatorial resident relative, S. t. axillaris. European stonechats are short-distance, nocturnal migrators that begin their journey when daylight lasts just over 12 hours. Since they would otherwise be sleeping at night, nocturnal activity can serve as a proxy for Zugunruhe. African stonechats are sedentary species that do not abandon their breeding grounds in Kenya. To investigate the presence of Zugunruhe in a resident species, the researchers raised and bred the offspring of Kenyan stonechats in their lab in Germany. One group of these birds was held for the duration of a migratory period under the nearly equal light and dark conditions of their native habitat, and a subset remained under these conditions for a year and a half. A control group was exposed to the natural seasonal light fluctuations of southern Germany. Helm and Gwinner recorded the birds’ nocturnal movements with infrared motion sensors, and counted the number of movements within ten-minute intervals. If 20 or more movements were noted, the interval was considered “active.”
Even though the African stonechats experienced no temporal cues—light levels remained constant—their nocturnal activity roughly tracked the season. The African birds’ migratory restlessness, marked by repeated, spontaneous outbursts of nocturnal activity, echoed that seen in European stonechats, though it was less pronounced. The African birds also showed a telling relationship between hatching date and onset of nocturnal activity: just like their migratory counterparts, late-hatching birds became restless earlier and earlier, coinciding with the migratory season.
The African birds’ behavior can be attributed only to Zugunruhe, the researchers concluded, suggesting the influence of an inborn, precisely timed migratory program. The presence of this program in both migrants and residents suggests that the urge to migrate may have evolved in their common ancestor. Helm and Gwinner propose that it may be a common avian feature. Given the proper environmental triggers, this innate migratory program might kick in to allow birds to escape deteriorating habitats caused by global climate changes or other ecological disturbances. With evidence that Zugunruhe exists in nonmigratory birds, researchers can continue exploring migratory behavior in any number of resident-migratory pairs to probe the many ways birds take flight to improve their chances of survival.
Citation: Helm B, Gwinner E (2006) Migratory restlessness in an equatorial nonmigratory bird. PLoS Biol 4(4): e110.
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