Making Blood Stem Cells Young Again

Stem Cells

Our blood stem cells generate around a thousand billion new blood cells every day. But the blood stem cells’ capacity to produce blood declines as we age. This leads to lowered immunity and other age related problems. Now for the first time, a research team at Lund University in Sweden has succeeded in rejuvenating blood stem cells that had become less functional in aging mice. The study is published in Nature Communications.

When we are young, our blood stem cells produce an even and well-balanced number of red and white blood cells according to need. As we age, however, the capacity of the blood stem cells to produce the number of blood cells we need declines.

“This type of age-related change can have major consequences as it can lead to an imbalance in stem cell production. For example, a reduced production of immune cells or excessive production of other types of cells” explains David Bryder, who headed the study at Lund University.

A fundamental question was whether blood stem cells age differently within a single individual or whether all blood stem cells are equally affected by advancing age. In an initial stage, it was therefore important to genetically mark old blood stem cells, to enable the identification and tracking of those most affected by age. In the next step, these traceable cells were reprogrammed to another type of stem cell known as iPS cells, which can generate all cells in an individual and not only blood cells. When the cells are reprogrammed, their identity is ?re-set”; when these reprogrammed iPS cells formed new blood stem cells, the researchers observed that the re-set had entailed a rejuvenation of the cells.

“We found that there was no difference in blood-generating capacity when we compared the reprogrammed blood stem cells with healthy blood stem cells from a young mouse. This is, as far as we know, the first time someone has directly succeeded in proving that it is possible to recreate the function of young stem cells from a functionally old cell?, says Martin Wahlestedt, the first author of the study.

The research team’s studies have also thereby shown that many age-related changes in the blood system cannot be explained by mutations in the cells’ DNA. If the changes depended on permanent damage at the DNA level, the damage would still be present after the re-set. Instead, epigenetic changes appear to underlie the decline in function associated with advancing age.

“Our findings justify further research to improve the function of human blood stem cells” concludes David Bryder.

Reference: Martin Wahlestedt, Eva Erlandsson, Trine Kristiansen, Rong Lu, Cord Brakebusch, Irving L. Weissman, Joan Yuan, Javier Martin-Gonzalez, David Bryder. Clonal reversal of ageing-associated stem cell lineage bias via a pluripotent intermediate. Nature Communications, 2017; 8: 14533 DOI: 10.1038/ncomms14533

Anti-Aging Benefits From Adipose Stem Cells

Adult Stem Cells

Adult stem cells collected directly from human fat have been used in stem cell treatments in many countries during the past 10 years. They are more stable than other cells such as fibroblasts from the skin and have the potential for use in anti-aging treatments, according to researchers from the Perelman School of Medicine at the University of Pennsylvania. They made the discovery after developing a new model to study chronological aging of these cells. They published their findings this month in the journal Stem Cells.

Chronological aging shows the natural life cycle of the cells as opposed to cells that have been unnaturally replicated multiple times or otherwise manipulated in a lab. In order to preserve the cells in their natural state, Penn researchers developed a system to collect and store them without manipulating them, making them available for this study. They found stem cells collected directly from human fat called adipose-derived stem cells (ASCs) can make more proteins than originally thought. This gives them the ability to replicate and maintain their stability, a finding that held true in cells collected from patients of all ages.

“Our study shows these cells are very robust, even when they are collected from older patients,” said Ivona Percec, MD, director of Basic Science Research in the Center for Human Appearance and the study’s lead author. “It also shows these cells can be potentially used safely in the future, because they require minimal manipulation and maintenance.”

Stem cells are currently used in a variety of anti-aging treatments and are commonly collected from a variety of tissues. But Percec’s team specifically found ASCs to be more stable than other cells, a finding that can potentially open the door to new therapies for the prevention and treatment of aging-related diseases.

“Unlike other adult human stem cells, the rate at which these ASCs multiply stays consistent with age,” Percec said. “That means these cells could be far more stable and helpful as we continue to study natural aging.”

ASCs are not currently approved for direct use by the Food and Drug Administration in the United States. Percec said the next step for her team is to study how chromatin is regulated in ASCs. Essentially, they want to know how tightly the DNA is wound around proteins inside these cells and how this affects aging. The more open the chromatin is, the more the traits affected by the genes inside will be expressed. Percec said she hopes to find out how ASCs can maintain an open profile with aging.

Can Adults Over 60 Gain Muscle Mass and Strength?

Jack LaLanne

You can rebuild them, even if you are middle-aged or older.

?Our lab and others have shown repeatedly? that older muscles will grow and strengthen, says Marcas Bamman, a professor of integrative biology at the University of Alabama at Birmingham. In his studies, men and women in their 60s and 70s who began supervised weight training developed muscles that were as large and strong as those of your average 40-year-old. Jack LaLanne continued to work out and maintain large and strong muscles until he passed away at the age of 96 years old.

The process of bulking up works differently in older people than in the young. Skeletal muscles are composed of various types of fibers and ?two things happen? to those fibers after we reach middle age, Dr. Bamman says. Some muscle fibers die, especially if we have not been exercising our muscles much. Sedentary adults can lose 30 to 40 percent of the total number of fibers in their muscles by the time they are 55, Dr. Bamman says.

Others of the fibers remain alive but shrink and atrophy as we age.

Young people who work out add new muscle fibers and also plump up their existing ones. Older people do not. We increase the size of our atrophied muscle fibers with exercise but, for a variety of physiological reasons, do not add to the number of fibers, Dr. Bamman says.

But in practical terms, who cares? Older muscles will become larger and stronger if you work them, Dr. Bamman says.

The key, he continues, is regular and progressive weight training. If you don?t belong to a gym, consider joining one, and then plan on tiring yourself. In order to initiate the biochemical processes that lead to larger, stronger fibers, Dr. Bamman says, you should push your muscles until they are exhausted.

In his studies, volunteers used weights calibrated so that the lifters could barely complete a set of eight to 12 repetitions before their arms or legs grew leaden and they had to rest. They repeated each set two or three times and visited the gym three times per week. If you are new to weight workouts, ask for an orientation at your gym or consult an athletic trainer who often works with older clients.

Reference: Bickel CS1, Cross JM, Bamman MM. Exercise dosing to retain resistance training adaptations in young and older adults. Med Sci Sports Exerc. 2011 Jul;43(7):1177-87.

Is “BPA Free” Safer Than BPA?

BPA Free

Companies advertise “BPA-free” as a safer version of plastic products ranging from water bottles to sippy cups to toys. Many manufacturers stopped using Bisphenol A to strengthen plastic after animal studies linked it to early puberty and a rise in breast and prostate cancers.

Yet new UCLA research demonstrates that BPS (Bisphenol S), a common replacement for BPA, speeds up embryonic development and disrupts the reproductive system.

Reported in the Feb. 1 edition of the journal Endocrinology, the animal study is the first to examine the effects of BPA and BPS on key brain cells and genes that control the growth and function of organs involved in reproduction.

“Our study shows that making plastic products with BPA alternatives does not necessarily leave them safer,” explained senior author Nancy Wayne, a reproductive endocrinologist and a professor of physiology at the David Geffen School of Medicine at UCLA.

Using a zebrafish model, Wayne and her colleagues found that exposure to low levels of BPA and BPS?equivalent to the traces found in polluted river waters?altered the animals’ physiology at the embryonic stage in as quickly as 25 hours.

“Egg hatching time accelerated, leading to the fish equivalent of premature birth,” said Wayne, who is also UCLA’s associate vice chancellor for research. “The embryos developed much faster than normal in the presence of BPA or BPS.”

The UCLA team, which included first author Wenhui Qiu, a visiting graduate student from Shanghai University, chose to conduct the study in zebrafish because their transparent embryos make it possible to “watch” cell growth as it occurs.

Using fluorescent-green protein tags, the researchers tracked the fishes’ development of reproductive endocrine brain cells, which control puberty and fertility. In a second finding, the team discovered that the number of endocrine neurons increased up to 40 percent, suggesting that BPA overstimulates the reproductive system.

“Exposure to low levels of BPA had a significant impact on the embryos’ development of brain cells that control reproduction, and the genes that control reproduction later in life,” said Wayne. “We saw many of these same effects with BPS found in BPA-free products. BPS is not harmless.”

Wayne suspects that overstimulation of the neurons that regulate reproduction could lead to premature puberty and disruption of the reproductive system. Her lab plans to investigate this question in a future study.

After uncovering her first finding about BPA in 2008, Wayne immediately discarded all of the plastic food containers in her home and replaced them with glass. She and her family purchase food and drinks packaged in glass whenever possible.

“Our findings are frightening and important,” emphasized Wayne. “Consider it the aquatic version of the canary in the coal mine.”

Finally, the researchers were surprised to find that both BPA and BPS acted partly through an estrogen system and partly through a thyroid hormone system to exert their effects.

“Most people think of BPA as mimicking the effects of estrogen. But our work shows that it also mimics the actions of thyroid hormone,” said Wayne. “Because of thyroid hormone’s important influence on brain development during gestation, our work holds important implications for general embryonic and fetal development, including in humans.”

Researchers have proposed that endocrine-disrupting chemicals may be contributing to the U.S.’ rise in premature human births and early onset of puberty over the past couple of decades.

“Our data support that hypothesis,” said Wayne. “If BPA is impacting a wide variety of animal species, then it’s likely to be affecting human health. Our study is the latest to help show this with BPA and now with BPS.”

BPA can leach into food, particularly under heat, from the lining of cans and from consumer products such as water bottles, baby bottles, food-storage containers and plastic tableware. BPA can also be found in contact lenses, eyeglass lenses, compact discs, water-supply pipes, some cash register and ATM receipts, as well as in some dental sealants and composites. The U.S. and Europe were expected to manufacture more than 5 million tons of products containing the additives in 2015.

Exercise For Long Telomeres, Too Much Sitting For Short Telomeres

Telomeres

A recent study showed that “cells age faster with a sedentary lifestyle. Chronological age doesn’t always match biological age,” according to Aladdin Shadyab, PhD, lead author of the study with the Department of Family Medicine and Public Health at UC San Diego School of Medicine.

Telomeres are tiny caps found on the ends of DNA strands, like the plastic tips of shoelaces, that protect chromosomes from deterioration. As a cell ages, its telomeres naturally shorten and fray, but health and lifestyle factors, such as obesity and smoking, may accelerate that process.

The study, publishing online January 18 in the American Journal of Epidemiology, found elderly women with less than 40 minutes of moderate-to-vigorous physical activity per day and who remain sedentary for more than 10 hours per day have shorter telomeres.

The researchers also found that elderly women who sit for more than 10 hours a day with low physical activity have cells that are biologically older by eight years compared to women who are less sedentary.

Shadyab and his research team believe they are the first to objectively measure how the combination of sedentary time and exercise can impact the aging biomarker.

Nearly 1,500 women, ages 64 to 95, participated in the study. The women are part of the larger Women’s Health Initiative (WHI), a national, longitudinal study investigating the determinants of chronic diseases in postmenopausal women. The participants completed questionnaires and wore an accelerometer on their right hip for seven consecutive days during waking and sleeping hours to track their movements.

“We found that women who sat longer did not have shorter telomere length if they exercised for at least 30 minutes a day, the national recommended guideline,” said Shadyab. “Discussions about the benefits of exercise should start when we are young, and physical activity should continue to be part of our daily lives as we get older, even at 80 years old.”

Shadyab said future studies will examine how exercise relates to telomere length in younger populations and in men.

Reference: Aladdin H. Shadyab et al. Associations of Accelerometer-Measured and Self-Reported Sedentary Time With Leukocyte Telomere Length in Older Women. American Journal of Epidemiology, January 2017 DOI: 10.1093/aje/kww196

Abstract: Few studies have assessed the association of sedentary time with leukocyte telomere length (LTL). In a cross-sectional study conducted in 2012?2013, we examined associations of accelerometer-measured and self-reported sedentary time with LTL in a sample of 1,481 older white and African-American women from the Women’s Health Initiative and determined whether associations varied by level of moderate- to vigorous-intensity physical activity (MVPA). The association between sedentary time and LTL was evaluated using multiple linear regression models. Women were aged 79.2 (standard deviation, 6.7) years, on average. Self-reported sedentary time was not associated with LTL. In a model adjusting for demographic characteristics, lifestyle behaviors, and health-related factors, among women at or below the median level of accelerometer-measured MVPA, those in the highest quartile of accelerometer-measured sedentary time had significantly shorter LTL than those in the lowest quartile, with an average difference of 170 base pairs (95% confidence interval: 4, 340). Accelerometer-measured sedentary time was not associated with LTL in women above the median level of MVPA. Findings suggest that, on the basis of accelerometer measurements, higher sedentary time may be associated with shorter LTL among less physically active women.