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

People who are overweight cut their life expectancy by two months for every extra kilogram (2.2 pounds) of weight they carry, research suggests.

A major study of the genes that underpin longevity has also found that education leads to a longer life, with almost a year added for each year spent studying beyond school.

Other key findings are that people who give up smoking, study for longer and are open to new experiences might expect to live longer.

Scientists at the University of Edinburgh analysed genetic information from more than 600,000 people alongside records of their parents’ lifespan.

Because people share half of their genetic information with each of their parents, the team were able to calculate the impact of various genes on life expectancy.

Lifestyle choices are influenced to a certain extent by our DNA/genes, for example, have been linked to increased alcohol consumption and addiction. The researchers were therefore able to work out which have the greatest influence on lifespan.

Their method was designed to rule out the chances that any observed associations could be caused by a separate, linked factor. This enabled them to pinpoint exactly which lifestyle factors cause people to live longer, or shorter, lives.

They found that cigarette smoking and traits associated with lung cancer had the greatest impact on shortening lifespan.

For example, smoking a packet of cigarettes per day over a lifetime knocks an average of seven years off life expectancy, they calculated. But smokers who give up can eventually expect to live as long as somebody who has never smoked.

Body fat and other factors linked to diabetes also have a negative influence on life expectancy.

The study also identified two new DNA differences that affect lifespan. The first is a gene that affects blood cholesterol levels and reduces lifespan by around eight months. The second is a gene linked to the immune system that adds around half a year to life expectancy.

The research, published in Nature Communications, was funded by the Medical Research Council.

Data was drawn from 25 separate population studies from Europe, Australia and North America, including the UK Biobank which is a major study into the role of genetics and lifestyle in health and disease.

Professor Jim Wilson, of the University of Edinburgh’s Usher Institute, said: “The power of big data and genetics allow us to compare the effect of different behaviours and diseases in terms of months and years of life lost or gained, and to distinguish between mere association and causal effect.”

Dr Peter Joshi, Chancellor’s Fellow at the University of Edinburgh’s Usher Institute, said: “Our study has estimated the causal effect of lifestyle choices. We found that, on average, smoking a pack a day reduces lifespan by seven years, whilst losing one kilogram of weight will increase your lifespan by two months.”

Reference: Peter K. Joshi, Nicola Pirastu, […], James F. Wilson. Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity. Nature Communications, 2017; 8 (1) DOI: 10.1038/s41467-017-00934-5

Researchers at the Institute of Molecular Biology (IMB) in Mainz have made a breakthrough in understanding the origin of the aging process. They have identified that genes belonging to a process called autophagy, which is one of the cells most critical survival processes, promote health and fitness in young worms but drive the process of aging later in life. This research published in the journal Genes & Development gives some of the first clear evidence for how the aging process arises as a quirk of evolution. The researchers show that by promoting longevity through shutting down autophagy in old worms there is a strong improvement in neuronal and subsequent whole body health.

Getting old is something that happens to everyone and nearly every species on this planet, but the question is: should it? In a recent publication in the journal Genes & Development titled “Neuronal inhibition of the autophagy nucleation complex extends lifespan in post-reproductive C. elegans,” Dr. Holger Richly’s lab at IMB has found some of the first genetic evidence that may put this question to rest.

According to Jonathan Byrne, co-lead author of the paper: “These AP genes had not been found before because it is incredibly difficult to work with already old animals. We were the first to figure out how to do this on a large scale. From a relatively small screen, we found a surprisingly large number of genes that seem to operate in an antagonistic fashion.” Previous studies had found genes that encourage aging while still being essential for development, but the 30 genes the IMB researchers found represent some of the first found promoting aging specifically only in old worms. “Considering we tested only 0.05 percent of all the genes in a worm this suggests there could be many more of these genes out there to find,” stated Byrne.

According to Thomas Wilhelm, the other co-lead author of the paper. “What was most surprising was what processes those genes were involved in.” Not content to provide just the missing evidence for a 60-year-old puzzle, Wilhelm and his colleagues went on to describe what a subset of these genes do in C. elegans and how they might be driving the aging process. “This is where the results really get fascinating,” emphasized Dr. Holger Richly, the principal investigator of the study. “We found a series of genes involved in regulating autophagy, which accelerate the aging process.” These results are surprising indeed as the process of autophagy is a critical recycling process in the cell and is usually required to live a normal full lifetime. Autophagy is known to become slower with age and the authors of this paper show that it appears to completely deteriorate in older worms. They demonstrate that shutting down key genes in the initiation of the process allows the worms to live longer compared with leaving it running crippled. “This could force us to rethink our ideas about one of the most fundamental processes that exist in a cell,” Richly explained. “Autophagy is nearly always thought of as beneficial even if it is barely working. We instead show that there are severe negative consequences when it breaks down and then you are better off bypassing it all together. It is classic AP: in young worms, autophagy is working properly and is essential to reach maturity, but after reproduction it starts to malfunction causing the worms to age,” he continued.

In a final revelation, Richly and his team were able to track the source of the pro longevity signals to a specific tissue, namely the neurons. By inactivating autophagy in the neurons of old worms they were not only able to prolong the worms life but they increased the total health of the worms dramatically. “Imagine reaching the halfway point in your life and getting a drug that leaves you as fit and mobile as someone half your age and you even live longer. That is what it is like for the worms,” said Thomas Wilhelm. “We turn autophagy off only in one tissue and the whole animal gets a boost. The neurons are much healthier in the treated worms and we think this keeps the muscles and the rest of the body in good shape. The net result is a 50 percent extension of life.”

While the authors do not yet know the exact mechanism causing the neurons to stay healthier for longer, this finding could have wide implications. “It is possible that these autophagy genes could represent a good way to help preserve neuronal integrity in these cases,” elaborated Thomas Wilhelm. While any such treatment would be a long way off, assuming such findings could be recapitulated in humans it offers a tantalising hope for being able to prevent disease and get younger and healthier while doing so.

Reference: Thomas Wilhelm, Jonathan Byrne, Rebeca Medina, Ena Kolund?i?, Johannes Geisinger, Martina Hajduskova, Baris Tursun, Holger Richly. Neuronal inhibition of the autophagy nucleation complex extends life span in post-reproductive C. elegans. Genes & Development, 2017; 31 (15): 1561 DOI: 10.1101/gad.301648.117

One of regenerative medicine’s most compelling questions is why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot. The answer may lie with the body’s innate immune system, according to a new study of heart regeneration in the axolotl, or Mexican salamander, an organism that takes the prize as nature’s champion of regeneration.

The study, which was conducted by James Godwin, Ph.D., of the MDI Biological Laboratory in Bar Harbor, Maine, found that the formation of new heart muscle tissue in the adult axolotl after a heart attack is dependent on the presence of macrophages, a type of white blood cell. When macrophages were depleted, the salamanders formed permanent scar tissue that blocked regeneration.

The study has significant implications for human health. Since salamanders and humans share many of the same genes, it’s possible that the ability to regenerate is also built into our genetic code.

Godwin’s research demonstrates that scar formation plays a critical role in blocking the program for regeneration. “The scar shoots down the program for regeneration,” he said. “No macrophages means no cardiac regeneration.”

Godwin’s goal is to activate regeneration in humans through the use of drug therapies derived from macrophages that would promote scar-free healing directly, or those that would trigger the genetic programs controlling the formation of macrophages, which in turn could promote scar-free healing. His team is already looking at molecular targets for drug therapies to influence these genetic programs.

“If humans could get over the fibrosis hurdle in the same way that salamanders do, the system that blocks regeneration in humans could potentially be broken,” Godwin explained. “We don’t know yet if it’s only scarring that prevents regeneration or if other factors are involved. But if we’re really lucky, we might find that the suppression of scarring is sufficient in and of itself to unlock our endogenous ability to regenerate.”

The prevailing view in regenerative biology has been that the major obstacle to heart regeneration in mammals is insufficient proliferation of cardiomyocytes, or heart muscle cells. But Godwin found that cardiomyocyte proliferation is not the only driver of effective heart regeneration. His findings suggest that research efforts should pay more attention to the genetic signals controlling scarring.

The extraordinary incidence of disability and death from heart disease, which is the world’s biggest killer, is directly attributable to scarring. When a human experiences a heart attack, scar tissue forms at the site of the injury. While the scar limits further tissue damage in the short term, over time its stiffness interferes with the heart’s ability to pump, leading to disability and ultimately to terminal heart failure.

In addition to regenerating heart tissue following a heart attack, the ability to unlock dormant capabilities for regeneration through the suppression of scarring also has potential applications for the regeneration of tissues and organs lost to traumatic injury, surgery and other diseases, Godwin said.

Godwin’s findings are a validation of the MDI Biological Laboratory’s unique research approach, which is focused on studying regeneration in a diverse range of animal models with the goal of gaining insight into how to trigger dormant genetic pathways for regeneration in humans. In the past year and a half, laboratory scientists have discovered three drug candidates with the potential to activate regeneration in humans.

“Our focus on the study of animals with amazing capabilities for regenerating lost and damaged body parts has made us a global leader in the field of regenerative medicine,” said Kevin Strange, Ph.D., MDI Biological Laboratory president. “James Godwin’s discovery of the role of macrophages in heart regeneration demonstrates the value of this approach: we won’t be able to develop rational and effective therapies to enhance regeneration in humans until we first understand regeneration works in animals like salamanders.”

Godwin, who is an immunologist, originally chose to look at the function of the immune system in regeneration because its role as the equivalent of a first responder at the site of an injury means that it is responsible for preparing the ground for tissue repairs. The recent study was a follow-up to an earlier study which found that macrophages also play a critical role in limb regeneration.

The next step is to study the function of macrophages in salamanders and compare them with their human and mouse counterparts. Ultimately, Godwin would like to understand why macrophages produced by adult mice and humans don’t suppress scarring in the same way as in axolotls and then identify molecules and pathways that could be exploited for human therapies.

Godwin holds a dual appointment with The Jackson Laboratory, also located in Bar Harbor, which is focused on the mouse as a model animal. The dual appointment allows him to conduct experiments that compare genetic programming in the highly regenerative animals used as models at the MDI Biological Laboratory with genetic programming in neonatal and adult mice.

Reference: J. W. Godwin, R. Debuque, E. Salimova, N. A. Rosenthal. Heart regeneration in the salamander relies on macrophage-mediated control of fibroblast activation and the extracellular landscape. npj Regenerative Medicine, 2017; 2 (1) DOI: 10.1038/s41536-017-0027-y

Scientists at The Scripps Research Institute (TSRI) have found a new approach to the “reprogramming” of ordinary adult cells into stem cells.

In a study published in an Advance Online paper in Nature Biotechnology, the TSRI scientists screened a library of 100 million antibodies and found several that can help reprogram mature skin-like cells into stem cells known as induced pluripotent stem cells (IPSCs).

Making IPSCs from more mature types of cells normally involves genetic engineering by inserting four transcription factor genes into the DNA of those cells. The new approach uses antibodies identified by the scientists that can be applied to mature cells where they bind to proteins on the cell surface as a substitute for three of the standard transcription factor gene insertions.

IPSCs that are made using genetic engineering have many unknown risks associated with them and are not currently utilized outside of research studies. This new discovery opens the possibility of taking a persons own cells, reverse aging them back into young stem cells and then using those to replace aged or damaged cells throughout the body.

“This result suggests that ultimately we might be able to make IPSCs without putting anything in the cell nucleus, which potentially means that these stem cells will have fewer mutations and overall better properties,” said study senior author Kristin Baldwin, associate professor in TSRI’s department of neuroscience.

IPSCs can be made from patients’ own cells, and have a multitude of potential uses in personalized cell therapies and organ regeneration. However, none of IPSCs’ envisioned clinical uses has yet been realized, in part because of the risks involved in making them.

The standard IPSC induction procedure, developed a decade ago and known as OSKM, involves the insertion into adult cells of genes for four transcription factor proteins: Oct4, Sox2, Klf4 and c-Myc. With these genes added and active, the transcription factor proteins they encode are produced and in turn reprogram the cells to become IPSCs.

One problem with this procedure is that this nuclear reprogramming typically yields a collection of IPSCs with variable properties. “This variability can be a problem even when we’re using IPSCs in the laboratory for studying diseases,” Baldwin said.

In contrast, during ordinary animal development, cell identity is altered by molecular signals that come in from outside the cell and induce changes in gene activity, without any risky insertions of DNA. To find natural pathways like these through which ordinary cells could be turned into IPSCs Baldwin and her laboratory teamed up with the TSRI laboratory of Richard Lerner, the Lita Annenberg Hazen Professor of Immunochemistry. Lerner has helped pioneer the development and screening of large libraries of human antibodies for finding new antibody-based drugs and scientific probes.

In this case, the team, including graduate student Joel W. Blanchard and postdoctoral research associate Jia Xie, who were lead authors, set up a library of about 100 million distinct antibodies and used it to find any that could substitute for OSKM transcription factors.

In an initial set of experiments, the researchers tried to identify antibodies that can replace both Sox2 and c-Myc. They established a large population of mouse fibroblast cells — often used to make IPSCs in experiments — and inserted the genes for the other two transcription factors, Oct4 and Klf4. Next they added their huge library of antibody genes to the population of cells, such that each cell ended up containing the genes for one or more of the antibodies.

The scientists could then observe which of the cells began forming stem cell colonies indicating that one of the antibodies produced by those cells had successfully replaced the functions of Sox2 and c-Myc and triggered the switch in cell identity. Sequencing the DNA of these cells allowed the researchers to determine the antibodies responsible.

In this way, the TSRI team discovered two antibodies that can be substituted for both Sox2 and c-Myc, and in a similar set of tests they found two antibodies that can replace a third transcription factor, Oct4. The scientists showed that instead of inserting these transcription factor genes they could simply supply the antibodies to the fibroblast cells in culture.

In this initial study, the scientists were unable to find antibodies that replace the function of the fourth OSKM transcription factor, Klf4. However, Baldwin expects that with more extensive screening she and her colleagues eventually will find antibody substitutes for Klf4 as well. “That one I think is going to take us a few more years to figure out,” she said.

The antibody-screening approach in principle allows scientists not only to find antibodies that can replace OSKM transcription factors, but also to study the natural signaling pathways through which these antibodies work.

In a proof of this principle, the scientists found that one of the Sox2-replacing antibodies binds to a protein on the cell membrane called Basp1. This binding event blocks Basp1’s normal activity and thus removes the restraints on WT1, a transcription factor protein that works in the cell nucleus. WT1, unleashed, then alters the activity of multiple genes, ultimately including Sox2’s, to promote the stem cell state using a different order of events than when using the original reprogramming factors.

The TSRI researchers now plan larger, more complex antibody-screening studies using human cells rather than mouse cells.

Reference: Joel W Blanchard, Jia Xie, Nadja El-Mecharrafie, Simon Gross, Sohyon Lee, Richard A Lerner, Kristin K Baldwin. Replacing reprogramming factors with antibodies selected from combinatorial antibody libraries. Nature Biotechnology, 2017; DOI: 10.1038/nbt.3963