While cognitive abilities naturally decline with age, eating one serving of leafy green vegetables a day may aid in preserving memory and thinking skills as a person grows older, according to a study by researchers at Rush University Medical Center in Chicago. The study results were published in the December 20, issue of Neurology, the medical journal of the American Academy of Neurology.

“Adding a daily serving of green leafy vegetables to your diet may be a simple way to help promote brain health,” said study author Martha Clare Morris, ScD, a nutritional epidemiologist at Rush. “There continues to be sharp increases in the percentage of people with dementia as the oldest age groups continue to grow in number. Effective strategies to prevent dementia are critically needed.”

The study results suggest that people who ate one serving of green, leafy vegetables had a slower rate of decline on tests of memory and thinking skills than people who rarely or never ate them. The study results also suggest that older adults who ate at least one serving of leafy green vegetables showed an equivalent of being 11 years younger cognitively.

960 older adults completed food questionnaires and received annual cognitive assessments

The study enlisted volunteers already participating in the ongoing Rush Memory and Aging Project, which began in 1997 among residents of Chicago-area retirement communities and senior public housing complexes. A “food frequency questionnaire” was added from 2004 to February 2013, which 1,068 participants completed. Of them, 960 also received at least two cognitive assessments for the analyses of cognitive change.

This study involved these 960 people, who at the study start were an average age of 81 years old and did not have dementia. They had their thinking and memory skills tested every year and were followed for an average of 4.7 years. The participants also completed the food frequency questionnaire, which assessed how often and how many half-cup servings they ate of either spinach; kale/collards/greens; or a one-cup serving of lettuce/salad.

The study divided the participants into five groups based on how often they ate green leafy vegetables, and compared the cognitive assessments of those who ate the most (an average of about 1.3 servings per day) and those who ate the least (0.1 servings per day).

Overall, the participants’ scores on the thinking and memory tests declined at a rate of 0.08 standardized units per year. Over 10 years of follow-up, the rate of decline for those who ate the most leafy greens was slower by 0.05 standardized units per year than the rate for those who ate the least leafy greens. This difference was equivalent to being 11 years younger in age, according to Morris.

More research needed in younger and minority populations

The results remained valid after accounting for other factors that could affect brain health, such as seafood and alcohol consumption, smoking, high blood pressure, obesity, education level and amount of physical and cognitive activities.

In remote Italian villages nestled between the Mediterranean Sea and mountains lives a group of several hundred citizens over the age of 90. Researchers at the University of Rome La Sapienza and University of California San Diego School of Medicine have identified common psychological traits in members of this group.

The study, publishing in International Psychogeriatrics, found participants who were 90 to 101 years old had worse physical health, but better mental well-being than their younger family members ages 51 to 75.

“There have been a number of studies on very old adults, but they have mostly focused on genetics rather than their mental health or personalities,” said Dilip V. Jeste MD, senior author of the study, senior associate dean for the Center of Healthy Aging and Distinguished Professor of Psychiatry and Neurosciences at UC San Diego School of Medicine. “The main themes that emerged from our study, and appear to be the unique features associated with better mental health of this rural population, were positivity, work ethic, stubbornness and a strong bond with family, religion and land.”

There were 29 study participants from nine villages in the Cilento region of southern Italy. The researchers used quantitative rating scales for assessing mental and physical health, as well as qualitative interviews to gather personal narratives of the participants, including topics such as migrations, traumatic events and beliefs. Their children or other younger family members were also given the same rating scales and additionally asked to describe their impressions about the personality traits of their older relatives.

“The group’s love of their land is a common theme and gives them a purpose in life. Most of them are still working in their homes and on the land. They think, ‘This is my life and I’m not going to give it up,'” said Anna Scelzo, first author of the study with the Department of Mental Health and Substance Abuse in Chiavarese, Italy.

Interview responses also suggested that the participants had considerable self-confidence and decision-making skills.

“This paradox of aging supports the notion that well-being and wisdom increase with aging even though physical health is failing,” said Jeste, also the Estelle and Edgar Levi Chair in Aging and director of the Sam and Rose Stein Institute for Research on Aging at UC San Diego.

Some direct quotes from the study’s interviews include:

?”I lost my beloved wife only a month ago and I am very sad for this. We were married for 70 years. I was close to her during all of her illness and I have felt very empty after her loss. But thanks to my sons, I am now recovering and feeling much better. I have four children, ten grandchildren and nine great-grandchildren. I have fought all my life and I am always ready for changes. I think changes bring life and give chances to grow.”

?”I am always thinking for the best. There is always a solution in life. This is what my father has taught me: to always face difficulties and hope for the best.”

?”I am always active. I do not know what stress is. Life is what it is and must be faced … always.”

?”If I have to say, I feel younger now than when I was young.”

“We also found that this group tended to be domineering, stubborn and needed a sense of control, which can be a desirable trait as they are true to their convictions and care less about what others think,” said Scelzo. “This tendency to control the environment suggests notable grit that is balanced by a need to adapt to changing circumstances.”

The researchers plan to follow the participants with multiple longitudinal assessments and compare biological associations with physical and psychological health.

“Studying the strategies of exceptionally long-lived and lived-well individuals, who not just survive but also thrive and flourish, enhances our understanding of health and functional capacities in all age groups,” said Jeste.

Reference: Anna Scelzo, Salvatore Di Somma, Paola Antonini, Lori P. Montross, Nicholas Schork, David Brenner, Dilip V. Jeste. Mixed-methods quantitative?qualitative study of 29 nonagenarians and centenarians in rural Southern Italy: focus on positive psychological traits. International Psychogeriatrics, 2017; 1 DOI: 10.1017/S1041610217002721

Abstract: This was a study of positive psychological traits in a group of rural Italians aged 90 to 101 years, and their children or other family members.

Mixed-methods quantitative (standardized rating scales) and qualitative (semi-structured interviews) study.

Study participants? homes in nine villages in the Cilento region of southern Italy.

Twenty-nine nonagenarians and centenarians and 51 family members aged 51?75 years, selected by their general practitioners as a part of a larger study called CIAO (Cilento Initiative on Aging Outcomes).

We used published rating scales of mental and physical well-being, resilience, optimism, anxiety, depression, and perceived stress. Qualitative interviews gathered personal narratives of the oldest-old individuals, including migrations, traumatic events, and beliefs. Family members described their impressions about the personality traits of their older relative.

Participants age ?90 years had worse physical health but better mental well-being than their younger family members. Mental well-being correlated negatively with levels of depression and anxiety in both the groups. The main themes that emerged from qualitative interviews included positivity (resilience and optimism), working hard, and bond with family and religion, as described in previously published studies of the oldest old, but also a need for control and love of the land, which appeared to be unique features of this rural population.

Exceptional longevity was characterized by a balance between acceptance of and grit to overcome adversities along with a positive attitude and close ties to family, religion, and land, providing purpose in life.

Cardiovascular diseases are a major cause of death worldwide, in part because the cells in our most vital organ do not get renewed. As opposed to blood, hair or skin cells that can renew themselves throughout life, our heart cells cease to divide shortly after birth, and there is very little renewal in adulthood. New research at the Weizmann Institute of Science provides insight into the question of why the mammalian heart fails to regenerate, on one hand, and demonstrated, in adult mice, the possibility of turning back this fate. This research appeared in Nature Cell Biology.

Prof. Eldad Tzahor of the Institute’s Biological Regulation Department thought that part of the answer to the regeneration puzzle might lie in his area of expertise: embryonic development, especially of the heart. Indeed, it was known that a protein called ERBB2 is well studied and plays a role in heart development. ERBB2 generally works together with a second, related, receptor by binding a growth factor called Neuregulin 1 (NRG1) to transmit messages into the cells. NGR1 is already being tested in clinical studies for treating heart failure.

Dr. Gabriele D’Uva, a postdoctoral fellow in the research group of Prof. Eldad Tzahor, wanted to know exactly how NRG1 and ERBB2 are involved in heart regeneration. In mice, new heart muscle cells can be added up to a week after birth; newborn mice can regenerate damaged hearts, while seven day old mice already cannot. D’Uva and research student Alla Aharonov observed that heart muscle cells called cardiomyocytes that were treated with NRG1 continued to proliferate on the day of birth; but the effect dropped dramatically within a week, even with ample amounts of NRG1. Further investigation showed that the difference between a day and a week was in the amount of ERBB2 on the cardiomyocyte membranes.

The team then created mice in which the gene for ERBB2 was knocked out only in cardiomyocytes. This had a severe impact: The mice had hearts with walls that were thin and balloon like a cardiac pathology known as dilated cardiomyopathy. The conclusion was that cardiomyocytes lacking ERBB2 do not divide, even in the presence of NRG1. Next, the team reactivated the ERBB2 protein in adult mouse heart cells, in which cardiomyocytes normally no longer divide. This resulted in extreme cardiomyocyte proliferation and hypertrophy excessive growth of the individual cardiomyocytes leading to a giant heart (cardiomegaly) that left little room for blood to enter. Tzahor: “Too little or too much of this protein had a devastating impact on heart function.”

If one could activate ERBB2 for just a short period in an adult heart following a heart attack, might it be possible to get the positive results, i.e., cardiac cell renewal, without such negative ones as hypertrophy and scarring? Testing this idea, the team found that they could, indeed, activate ERBB2 in mice for a short interval only following an induced heart attack and obtain nearly complete heart regeneration within several weeks. “The results were amazing,” says Tzahor. “As opposed to extensive scarring in the control hearts, the ERBB2-expressing hearts had completely returned to their previous state.”

Investigation of the regenerative process through live imaging and molecular studies revealed how this happens: The cardiomyocytes “dedifferentiate” that is, they revert to an earlier form, something between an embryonic and an adult cell, which can then divide and differentiate into new heart cells. In other words, the ERBB2 took the cells back a step to an earlier, embryonic form; and then stopping its activity promoted the regeneration process.

In continuing research, Tzahor and his team began to outline the pathway the other proteins that respond to the NRG1 message inside the cell. “ERBB2 is clearly at the top of the chain. We have shown that it can induce cardiac regeneration on its own. But understanding the roles of the other proteins in the chain may present us with new drug targets for treating heart disease,” says D’Uva.

Tzahor points out that clinical trials of patients receiving the NRG1 treatment might not be overly successful if ERBB2 levels are not boosted as well. He and his team plan to continue researching this signaling pathway to suggest ways of improving the process, which may, in the future, point to ways of renewing heart cells. Because this pathway is also involved in cancer, well-grounded studies will be needed to understand exactly how to direct the cardiomyocyte renewal signal at the right place, the right time and in the right amount. “Much more research will be required to see if this principle could be applied to the human heart, but our findings are proof that it may be possible,” he says.

Reference: Gabriele D?Uva, Alla Aharonov, Mattia Lauriola, David Kain, Yfat Yahalom-Ronen, Silvia Carvalho, Karen Weisinger, Elad Bassat, Dana Rajchman, Oren Yifa, Marina Lysenko, Tal Konfino, Julius Hegesh, Ori Brenner, Michal Neeman, Yosef Yarden, Jonathan Leor, Rachel Sarig, Richard P. Harvey, Eldad Tzahor. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Biology, 2015; DOI: 10.1038/ncb3149

Back in 2007 scientists announced that they had created embryonic like stem cells from adult human skin cells. IPS cells (induced pluripotent stem cells) have been very valuable in research, however converting them into any type of cell that could be used for actual stem cell therapy is extremely complicated and far from becoming safe or available. Embryonic stem cells exist to create an entire organism not to repair an adult. A new breakthrough allows researchers to take differentiated cells from potentially any part of the body and reverse age them without going all the way back to an embryonic like state. In a study of mice these have already been used successfully for cell replacement therapy. This may be the breakthrough needed to rebuild damaged, diseased or old organs with a few injections back to a young and healthy condition in the not too distant future.

A modified version of iPS methodology, the new approach is called interrupted reprogramming and it allows for a highly controlled, potentially safer, and more cost-effective strategy for generating progenitor-like cells from adult cells. As demonstrated November 30 in the journal Stem Cell Reports, researchers in Canada converted adult mouse respiratory tract cells called Club cells into large, pure populations of induced progenitor-like (iPL) cells, which retained a residual memory of their parental cell lineage and therefore specifically generated mature Club cells. Moreover, these cells showed potential as a cell replacement therapy in mice with cystic fibrosis.

“A major block in the critical path of regenerative medicine is the lack of suitable cells to restore function or repair damage,” says co-senior author Tom Waddell, a thoracic surgeon at the University of Toronto. “Our approach starts with purifying the cell type we want and then manipulating it to give those cell types characteristics of progenitor cells, which can grow rapidly but produce only a few cell types. As such, it is much more direct, more rapid, and the batches of cells are more purified.”

In recent years, induced pluripotent stem (iPS) cells have generated a great deal of interest as a potentially unlimited source of various cell types for transplantation. This method involves genetically reprogramming skin cells taken from adult donors to an embryonic stem-cell-like state, growing these immature cells to large numbers, and then converting them into specialized cell types found in different parts of the body. A major advantage of this approach is the ability to generate patient-specific iPS cells for transplantation, thereby minimizing the risk of harmful immune reactions.

Despite significant progress, these protocols remain limited by low yield and purity of the desired mature cell types, as well as the potential of immature cells to form tumors. Moreover, there is no standardized approach applicable to all cell types, and the development of personalized therapies based on patient-derived pluripotent cells remains very expensive and time consuming. “We have pursued cell therapy for lung diseases for many years,” Waddell says. “One key issue is how to get the right type of cells and lots of them. To avoid rejection, we need to use cells from the actual patient.”

To address these issues, Waddell and co-senior study author Andras Nagy of Mount Sinai Hospital developed an interrupted reprogramming strategy, which is a modified version of the iPS methodology. The researchers started to genetically reprogram adult Club cells isolated from mice, transiently expressing the four iPS reprogramming factors, but interrupted the process early, prior to reaching the pluripotent state, to generate progenitor-like cells, which are more committed to a specific lineage and show more controlled proliferation than pluripotent cells.

“The reprogramming process had previously been considered as an all-or-none process,” Waddell says. “We were surprised to the extent that it can be fine-tuned by the timing and dosing of the drug used to activate the reprogramming factors. That is interesting as it gives lots of opportunities for control, but it does mean we have lots of work to do to get it right.”

The researchers showed that the resulting Club-iPL cells could give rise to not only Club cells, but also to other respiratory tract cells such as mucus-secreting goblet cells and ciliated epithelial cells that produce the CFTR protein, which is mutated in patients with cystic fibrosis. When the Club-iPL cells were administered to CFTR-deficient mice, the cells incorporated into tissue lining the respiratory tract and partially restored levels of CFTR in the lungs without inducing tumor formation. This technology can theoretically be applied to almost any cell type that can be isolated and purified, and isolation of highly purified populations of adult cells from most organs is already possible with existing techniques.

“To create specialized cell types for use in cell therapy requires only that we insert the genes (or use non-transgenic approaches) and then test the drug dose and timing required for each cell type and each patient, so it should be relatively scalable at low cost compared to other approaches using each patient’s own cells,” Waddell says. “It should be very easy for other labs to use a similar approach.”

According to the authors, the approach could be used for a variety of regenerative medicine practices, including cell replacement therapy, disease modelling, and drug screening for human diseases. But there is still a long way to go before clinical translation. For their own part, the researchers plan to test this approach with other cell types, including human cells. They will also try to determine if there are safe ways to engraft these cells in human lungs. “The study is a proof of principle, the way this concept may ultimately be used in humans could be different, and it will be many years before this will be attempted in humans,” Waddell says.

Reference: Li Guo, Golnaz Karoubi, Pascal Duchesneau, Maria V. Shutova, Hoon-Ki Sung, Peter Tonge, Christine Bear, Ian Rogers, Andras Nagy, Thomas K. Waddell. Generation of Induced Progenitor-like Cells from Mature Epithelial Cells Using Interrupted Reprogramming. Stem Cell Reports, 2017; DOI: 10.1016/j.stemcr.2017.10.022

A researcher at the School of Medicine and his colleagues have succeeded in isolating mouse lung stem cells, growing them in large volumes and incorporating them into injured lung tissue in mice.

The work raises hopes for regenerative therapies that could heal currently intractable lung diseases.

A study describing the research was published online Nov. 6 in Nature Methods. Kyle Loh, PhD, an investigator at the Stanford Institute for Stem Cell Biology and Regenerative Medicine, and Bing Lim, MD, PhD, an investigator at the Genome Institute of Singapore, share senior authorship. The lead author is Massimo Nichane, PhD, currently a research scientist at the Stanford stem cell institute.

The lungs are among the most vital organs of the body. In conjunction with the cardiovascular system, they allow air to travel to every cell and get rid of the waste products of respiration, such as carbon dioxide. For many people with end-stage lung diseases, the only option is lung transplantation.

“Scientists have previously had little success in putting new lung cells into damaged lung to regenerate healthy tissue,” Loh said. “We decided to see if we could do that in an animal model.”

The researchers started by working to improve on current knowledge of lung stem cells. The lung is divided into two compartments, Loh said: the airway, which allows for passage of air in and out of the lung; and the alveoli, where gases pass in and out of the blood. Other researchers had previously isolated one stem cell for the airway and another stem cell for the alveoli. Loh and his colleagues searched for and found a single lung stem cell that could create cells in both the airway and the alveoli. These multipotent lung stem cells were typified by their display of a protein marker called Sox9.

Once they had isolated the stem cells, they were able to make them multiply dramatically. Each mouse lung stem cell that they start started with was able to grow into 100 billion billion lung stem cells over the course of six months. Previously, researchers had not had much success expanding any lung stem cell populations in the laboratory.

Finally, they injected the stem cells into mouse lungs that had been injured by a variety of toxins. “What we saw was that these multipotent stem cells repaired the injured tissue and were able to differentiate into the many different kinds of cells that make up the healthy lung,” said Nichane.

“Our newfound ability to grow these mouse multipotent lung stem cells in a petri dish in very large numbers, and the cells’ ability to regenerate both lung airway and alveolar tissue, constitutes a first step towards future lung regenerative therapies,” Loh said. “Future work will focus on whether analogous multipotent stem cells can be found and cultivated from humans, which may open the way to eventually replenishing damaged lung tissue in the clinic.”

Reference: Massimo Nichane et al. Isolation and 3D expansion of multipotent Sox9+ mouse lung progenitors, Nature Methods (2017). DOI: 10.1038/nmeth.4498

Engineered tissue containing human stem cells has allowed paraplegic rats to walk independently and regain sensory perception. The implanted rats also show some degree of healing in their spinal cords. The research, published in Frontiers in Neuroscience, demonstrates the great potential of stem cells undifferentiated cells that can develop into numerous different types of cells to treat spinal cord injury.

Spinal cord injuries often lead to paraplegia. Achieving substantial recovery following a complete spinal cord tear, or transection, is an as-yet unmet challenge.

Led by Dr. Shulamit Levenberg, of the Technion-Israel Institute of Technology, the researchers implanted human stem cells into rats with a complete spinal cord transection. The stem cells, which were derived from the membrane lining of the mouth, were induced to differentiate into support cells that secrete factors for neural growth and survival.

The work involved more than simply inserting stem cells at various intervals along the spinal cord. The research team also built a three-dimensional scaffold that provided an environment in which the stem cells could attach, grow and differentiate into support cells. This engineered tissue was also seeded with human thrombin and fibrinogen, which served to stabilize and support neurons in the rat’s spinal cord.

Rats treated with the engineered tissue containing stem cells showed higher motor and sensory recovery compared to control rats. Three weeks after introduction of the stem cells, 42% of the implanted paraplegic rats showed a markedly improved ability to support weight on their hind limbs and walk. 75% of the treated rats also responded to gross stimuli to the hind limbs and tail.

In contrast, control paraplegic rats that did not receive stem cells showed no improved mobility or sensory responses.

In addition, the lesions in the spinal cords of the treated rats subsided to some extent. This indicates that their spinal cords were healing.

While the results are promising, the technique did not work for all implanted rats. An important area for further research will be to determine why stem cell implantation worked in some cases but not others. As the research team notes, “This warrants further investigation to shed light on the mechanisms underlying the observed recovery, to enable improved efficacy and to define the intervention optimal for treatment of spinal cord injury.”

Although the study in itself does not solve the challenge of providing medical treatments for spinal cord injury in humans, it nevertheless points the way to that solution. As Dr. Levenberg puts it: “Although there is still some way to go before it can be applied in humans, this research gives hope.”

Reference: Javier Ganz, Erez Shor, Shaowei Guo, Anton Sheinin, Ina Arie, Izhak Michaelevski, Sandu Pitaru, Daniel Offen, Shulamit Levenberg. Implantation of 3D Constructs Embedded with Oral Mucosa-Derived Cells Induces Functional Recovery in Rats with Complete Spinal Cord Transection. Frontiers in Neuroscience, 2017; 11 DOI: 10.3389/fnins.2017.00589

Easy strength training exercises which require no equipment such as wall push ups or ordinary push ups could add years to your life according to a new study of over 80,000 adults led by the University of Sydney.

The largest study to compare the mortality outcomes of different types of exercise found people who did strength-based exercise had a 23 percent reduction in risk of premature death by any means, and a 31 percent reduction in cancer-related death.

Lead author Associate Professor Emmanuel Stamatakis from the School of Public Health and the Charles Perkins Centre said while strength training has been given some attention for functional benefits as we age, little research has looked at its impact on mortality.

“The study shows exercise that promotes muscular strength may be just as important for health as aerobic activities like jogging or cycling,” said Associate Professor Stamatakis.

“And assuming our findings reflect cause and effect relationships, it may be even more vital when it comes to reducing risk of death from cancer.”

The World Health Organization’s Physical Activity Guidelines for adults recommend 150 minutes of aerobic activity, plus two days of muscle strengthening activities each week.

Associate Professor Stamatakis said governments and public health authorities have neglected to promote strength-based guidelines in the community, and as such misrepresented how active we are as a nation.

He cites the example of The Australian National Nutrition and Physical Activity Survey which, based on aerobic activity alone, reports inactivity at 53 percent. However, when the World Health Organization’s (WHO) strength-based guidelines are also taken into account, 85 percent of Australians fail to meet recommendations.

“Unfortunately, less than 19 percent of Australian adults do the recommended amount of strength-based exercise,” said Associate Professor Stamatakis.

“Our message to date has just been to get moving but this study prompts a rethink about, when appropriate, expanding the kinds of exercise we are encouraging for long-term health and wellbeing.”

The analysis also showed exercises performed using one’s own body weight without specific equipment were just as effective as gym-based training.

“When people think of strength training they instantly think of doing weights in a gym, but that doesn’t have to be the case.

“Many people are intimidated by gyms, the costs or the culture they promote, so it’s great to know that anyone can do classic exercises like triceps dips, sit-ups, push-ups or lunges in their own home or local park and potentially reap the same health benefits.”

The research, published in the American Journal of Epidemiology today, is based on a pooled population sample of over 80,306 adults with data drawn from the Health Survey for England and Scottish Health Survey, linked with the NHS Central Mortality Register.

The study was observational, however adjustments were made to reduce the influence of other factors such as age, sex, health status, lifestyle behaviours and education level. All participants with established cardiovascular disease or cancer at baseline and those who passed away in the first two years of follow up were excluded from the study to reduce the possibility of skewing results due to those with pre-existing conditions participating in less exercise.

Key findings:

?Participation in any strength-promoting exercise was associated with a 23 percent reduction in all-cause mortality and a 31 percent reduction in cancer mortality

?Own bodyweight exercises that can be performed in any setting without equipment yielded comparable results to gym-based activities

?Adherence to WHO’s strength-promoting exercise guideline alone was associated with reduced risk of cancer-related death, but adherence to the WHO’s aerobic physical activity guideline alone was not

?Adherence to WHO’s strength-promoting exercise and aerobic guidelines combined was associated with a greater risk reduction in mortality than aerobic physical activity alone

?There was no evidence of an association between strength-promoting exercise and cardiovascular disease mortality.

Reference: Emmanuel Stamatakis, I-Min Lee, Jason Bennie, Jonathan Freeston, Mark Hamer, Gary O’Donovan, Ding Ding, Adrian Bauman, Yorgi Mavros. Does strength promoting exercise confer unique health benefits? A pooled analysis of eleven population cohorts with all-cause, cancer, and cardiovascular mortality endpoints. American Journal of Epidemiology, 2017; DOI: 10.1093/aje/kwx345

As scientists work to unlock the mysteries of why some 80-year-olds play tennis every week while others must live in nursing homes, researchers with the University of Miami?s Interdisciplinary Stem Cell Institute report they have found the beginnings of what may be the first therapeutic treatment for frailty, a common condition of aging that can lead to falls and other adverse effects. An early stage clinical trial conducted in Miami found that elderly patients breathed easier and walked longer distances after receiving a single infusion of stem cells from young and healthy donors.

Scientists have been making significant headway recently, studying a variety of anti-aging targets from discovering a protein that can restore hair and improve fitness in old mice to revealing how fecal transplants increase the lifespan of some fish. But the arena of stem cell transplantation has offered some of the most exciting anti-aging research outcomes.

Mesenchymal stem cells (MSCs) are a particular type of adult stem cell generating a great deal of interest in the world of science. MSCs are currently being trialed as treatment for no less than a dozen different types of conditions.

The results of two human clinical trials into a stem cell therapy that can reverse symptoms of age-associated frailty have been published, and the indications are that this landmark treatment is both safe and strikingly effective in tackling key factors in aging.

This new MSC treatment is targeted at reducing the effects of frailty on senior citizens. This is the first anti-aging stem cell treatment directed specifically at the problem of age-associated frailty to move close to a final FDA approval stage.

The treatment derives human mesenchymal stem cells from adult donor bone marrow and in these clinical trials involves a single infusion in patients with an average age of 76. Both Phase 1 and Phase 2 human trials have demonstrated the treatment to have no adverse health effects.

Although the two human trials were ostensibly designed to just demonstrate safety they do offer remarkable results in efficacy as well, paving the way for larger, Phase 3 clinical trials.

In the first trial 15 frail patients received a single MSC infusion collected from bone marrow donors aged between 20 and 45 years old. Six months later all patients demonstrated improved fitness outcomes, tumor necrosis factor levels and overall quality of life.

The second trial was a randomized, double blind study with placebo group. Again no adverse affects were reported and physical improvements were noted by the researchers as “remarkable”.

“There are always caveats associated with interpreting efficacy in small numbers of subjects, yet it is remarkable that a single treatment seems to have generated improvement in key features of frailty that are sustained for many months,” writes David G. Le Couter and colleagues in a guest editorial in The Journals of Gerontology praising the research.

The next stage for the research is to move into an expanded Phase 2b clinical trial involving 120 subjects across 10 locations. After that a final, large randomized Phase 3 clinical trial will be the only thing holding the treatment back from final public approval by the FDA.

“With the aging of the population, stem cells hold great promise to treat aging-related disability and frailty, improving physical capacity and quality of life,” says one of the scientists working on the project Joshua M. Hare, Director of the Interdisciplinary Stem Cell Institute at the University of Miami Miller School of Medicine.

“There is no FDA approved treatment for aging frailty and an enormous unmet need that will only increase with the changing demographics.”

The results of the Phase 1 and Phase 2 clinical trials were recently published in The Journals of Gerontology.

References

Phase 1 Trial: Samuel Golpanian Darcy L DiFede Aisha Khan Ivonne Hernandez Schulman Ana Marie Landin Bryon A Tompkins Alan W Heldman Roberto Miki Bradley J Goldstein Muzammil Mushtaq Silvina Levis-Dusseau John J Byrnes Maureen Lowery Makoto Natsumeda Cindy Delgado Russell Saltzman Mayra Vidro-Casiano Marietsy V Pujol Moisaniel Da Fonseca Anthony A Oliva, Jr Geoff Green Courtney Premer Audrey Medina Krystalenia Valasaki Victoria Florea Erica Anderson Jill El-Khorazaty Adam Mendizabal Pascal J Goldschmidt-Clermont Joshua M Hare; Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty; The Journals of Gerontology: Series A, Volume 72, Issue 11, 12 October 2017, Pages 1505?1512, https://doi.org/10.1093/gerona/glx056

Phase 2 Trial: Bryon A Tompkins, MD Darcy L DiFede, RN, BSN Aisha Khan, Msc, MBA Ana Marie Landin, PhD Ivonne Hernandez Schulman, MD Marietsy V Pujol, MBA Alan W Heldman, MD Roberto Miki, MD Pascal J Goldschmidt-Clermont, MD Bradley J Goldstein, MD Muzammil Mushtaq, MD Silvina Levis-Dusseau, MD John J Byrnes, MD Maureen Lowery, MD Makoto Natsumeda, MD Cindy Delgado, MA, CCRC Russell Saltzman, BS.Ed Mayra Vidro-Casiano, MPH Moisaniel Da Fonseca, AA Samuel Golpanian, MD Courtney Premer, PhD Audrey Medina, BSc Krystalenia Valasaki, MSc Victoria Florea, MD Erica Anderson, MA Jill El-Khorazaty, MS Adam Mendizabal, PhD Geoff Green, BA, MBA Anthony A Oliva, PhD Joshua M Hare, MD; Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial; The Journals of Gerontology: Series A, Volume 72, Issue 11, 12 October 2017, Pages 1513?1522, https://doi.org/10.1093/gerona/glx137