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Thanks for reading The Abstract. This month’s edition is
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Welcome to the April edition of
The Abstract. In honor of National DNA Day on April 25, we’ve got an array of genetics-related research for you—chromosomes, epigenetics, telomeres, and more. Our headline study explores how the “reawakening” of the silent X chromosome in women leads to better cognitive aging in later life, potentially offering future directions for healthy aging interventions. Also in this month’s longevity newsletter: the role of inflammation in telomere length, how heat accelerates epigenetic aging, a surprising study challenging the role of exercise in longevity, and more data on eating for healthy aging.
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Why women’s brains age better: the ‘silent’ X chromosome
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Micrograph of chromosomes from a mouse cell. Red indicates the inactive X chromosome. Credit: Ng K et al. EMBO Reports 2007, 8: 34
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Women tend to outlive men and retain their cognitive capacities longer. A new study from researchers at UCSF offers a possible explanation: the second X chromosome, previously thought to be “silent” or not expressing genes. A study on mice found that the typically inactive second X chromosome in females “reawakens” later in life. In 20-month-old female mice (equivalent to 65-year-old humans), 22 genes from the silent X chromosome were found to be expressed in the hippocampus, which is responsible for memory and learning—and deteriorates with age. One gene called PLP1 stood out to researchers because it helps build myelin, the neural insulation that surrounds the brain’s wires and allows them to transmit signals. The evidence for the importance of PLP1 was strong: Older female mice had more PLP1 than older male mice, boosting PLP1 in older mice of both sexes improved cognition, and donated human brain tissue from older men and women found elevated PLP1 exclusively in women. Future research may explore
brain aging interventions that boost PLP1.
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The Expert's Take:
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“Why is it that women, compared to men, live longer and experience a slower decline in key brain functions such as memory during aging? Although many factors contribute to these age and sex related differences in brain health, this exciting paper suggests that a very specific and surprising aspect of aging is responsible for at least some of these differences, in both mice and humans. To understand this effect, we must first recall that females have two X chromosomes, while males have only one. This difference would lead to an imbalance in the expression of many genes, if it were not for the fact one of the two X chromosomes carried by females is normally silenced. This phenomenon of X-inactivation is a fascinating and complex aspect of gene regulation, but the end result is simple: both males and females have only one ‘active’ X chromosome.
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As might be expected, the tight control of X-chromosome gene expression starts to break down with aging. As a result, both in women and in female mice, some of the genes on the inactive X start to be expressed, leading to higher than normal expression. One might expect that this would be a bad thing in general, and for many genes that may be the case. The authors of this paper zeroed in on one of these genes, which is expressed in a particular part of the brain that is responsible for memory. Their striking observation is that this gene becomes over-expressed in the aging female brain, raising the question of whether this over expression is a cause or a consequence of the better retention of cognitive function in aging females. To address this point the authors artificially increased the expression of this gene, and found an improvement in cognitive function in both male and female aging mice. How this gene exerts its protective effect remains unclear, but changes in the epigenetic factors that control X-inactivation are likely to play a role. Understanding these effects in more detail may eventually lead to a better understanding of how to maintain brain health during aging, for both men and women.”
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Jack Szostak, Ph.D.
University Professor of chemistry at the University of Chicago, Howard Hughes Medical Institute investigator, 2009 Nobel Laureate in Physiology or Medicine, and member of the Elysium Scientific Advisory Board
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THIS MONTH
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What We're Reading
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These are third-party articles about science that we find interesting but have no relationship to Elysium or any of our products. Elysium’s products are not intended to screen, diagnose, treat, cure, or prevent any disease.
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Diet, lifestyle, and your telomeres
Telomeres are the protective caps at the end of our chromosomes that get shorter as we age—impacting our cells’ ability to divide correctly and contributing to age-related diseases. A new study looks at the relationship between diet, lifestyle factors, and telomere length. Researchers used a sophisticated statistical technique called Copula Graphical Modeling (CGM) to investigate the connection between leukocyte telomere length (TL) and over 100 demographic, dietary, lifestyle, and blood variables in 7,096 U.S. adults. They found the strongest associations between telomere length and age (not surprisingly), the marker of inflammation C-reactive protein (CRP), and gamma-tocopherol, a form of vitamin E found in the blood and linked to poor health. Direct links to dietary and lifestyle factors were weak, suggesting that inflammation—represented by CRP—may be intermediary between harmful lifestyle choices and telomere length. (Aging)
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Heat can accelerate aging—as much as smoking
Extreme heat can accelerate aging. People who live in areas with long periods of hot days tend to have accelerated epigenetic aging, according to a new study. People who live in hot climates like Phoenix with ≥90°F temperatures half the year were roughly 14 months older,
epigenetically, compared to people who live in cooler climates like Seattle with less than 10 heat days per year. Hot climates were determined based on a location’s heat index history and the number of heat days reported by the National Weather Service from 2010 to 2016. The study’s lead author, Eunyoung Choi, Ph.D., said that the impact is
"similar to the effect of smoking and drinking." While the data in the study was adjusted for various sociodemographic factors, including people’s financial status, education, physical activity, and whether they smoked, the study is correlational and requires further research. (Science Advances)
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Does exercise actually extend life?
It’s common knowledge that exercise is a key to longevity—but new research on 22,750 Finnish twins followed over 30 years suggests there’s more to the story. Scientists at the University of Jyväskylä investigated the link between long-term physical activity, mortality, and biological aging. Based on their activity, the participants were grouped as sedentary, moderately active, active, and highly active groups. While higher activity was associated with lower mortality in the short term, in the long term the greatest benefit—a 7% reduction in mortality—was achieved with moderate activity equivalent to the World Health Organization guidelines for the recommended minimum amount of physical activity (150 min of moderate intensity physical activity per week). No additional benefits were achieved by higher levels of activity. Finally,
biological aging, measured using epigenetic clocks, was accelerated in those who exercised the least and those who exercised the most. According to the study authors, the dose-dependent association between exercise and mortality reported in previous observational studies may be explained by bias—such as underlying health status and other lifestyle factors like education, alcohol use, and BMI. (European Journal of Epidemiology)
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How to eat for healthy aging
The search for the holy grail diet for longevity continues. A new study led by researchers at Harvard T.H. Chan School of Public Health assessed the role of multiple diets in healthy aging—defined as reaching age 70 free of major chronic diseases and with cognitive, physical, and mental health maintained. Researchers analyzed the diets of more than 105,000 health professionals ages 39-69 over the course of 30 years. Of these, 9.3% achieved healthy aging, and the most advantageous diet was the Alternative Healthy Eating Index (AHEI), which is rich in fruits, vegetables, whole grains, nuts, legumes, and healthy fats, and low in red and processed meats, sugar-sweetened beverages, sodium, and refined grains. Not surprisingly, higher intakes of ultra-processed foods, especially processed meat and sugary (and diet) drinks was associated with worse changes of healthy aging. (Nature Medicine)
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TERM OF THE MONTH
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Biological age
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/ˌbaɪ.əˈlɑː.dʒɪ.kəl/ /eɪdʒ/
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Everyone ages at a different rate. While genetics play a role—accounting for an estimated 25% of the variation—lifestyle and environment have a greater influence. Unlike chronological age, which simply counts your years, biological age reflects how well your body is functioning. It offers a more accurate picture of your overall health. Biological age is calculated using epigenetics—chemical tags on your DNA that influence how your genes are expressed. These epigenetic markers are dynamic and responsive to your behavior. By tracking your biological age over time, you can see how your diet, exercise, sleep, and other lifestyle choices are shaping the pace of your aging process.
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AGING 101
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Epigenetics, DNA methylation, and the science of biological clocks
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Our DNA makes us who we are, but it’s epigenetics that brings our story to life. Here’s the science of epigenetics, including how it works and how it relates to biological clocks. (Read more)
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