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City of Hope Scientists Have Developed a Precision Medicine Tool That Predicts If Chemotherapy Will Produce Debilitating Side Effects in Older Adults…

DUARTE, Calif.--(BUSINESS WIRE)--Researchers at City of Hope, a world-renowned independent research and treatment center for cancer, diabetes and other life-threatening diseases, have developed a tool that could predict if older adults with early-stage breast cancer will develop a severe or deadly reaction to chemotherapy.

This first-of-its-kind risk assessment tool called the Cancer and Aging Research Group-Breast Cancer (CARG-BC) Score helps oncologists make personalized treatment recommendations. Oncologists can discuss the score and its significance with early-stage breast cancer patients age 65 or older. Together, an informed decision about chemotherapy can be made as treatment benefit is weighed against quality of life concerns, said Mina Sedrak, M.D., M.S., co-first author of the new study and deputy director of clinical trials for the Center for Cancer and Aging Research at City of Hope.

Despite remarkable advances in cancer treatment, tools to characterize the toxicity of cancer therapies have remained virtually unchanged for the past 20 years, Sedrak said. This is a new precision medicine tool. Rather than basing treatment decisions and care on demographic data for a disease, we now can offer each elderly, early-stage breast cancer patient individualized toxicity information that could help align treatment with their goals for lifestyle, quality of life, longevity and other priorities.

More than 72% of older patients with cancer reported that they would not choose cancer treatment that results in functional impairment even if it improves survival, Sedrak said.

If the risk of chemotherapy toxicity is known in advance, oncologists and patients could work together to decide whether chemotherapy is the right choice. Treatment modifications such as dose reductions and longer periods between chemotherapy delivery could be recommended. Older patients could also preemptively be referred for supportive care interventions such as consults with physical therapists, occupational therapists, social workers and pharmacists, who could evaluate potential drug interactions with existing medications for chronic ailments. Additionally, patients could have someone evaluate their home for safety or necessary modifications.

The study, published on Jan. 14 in the Journal of Clinical Oncology, spanned 16 institutions across the nation, with City of Hope being the lead institution. It included 473 patients age 65 or older with Stage 1-3 breast cancer (283 in development cohort; 190 in validation cohort). They were all treated with chemotherapy either before or after surgery and were evaluated for geriatric and clinical symptoms predictive of severe (grade 3), debilitating (grade 4) or deadly (grade 5) side effects due to chemotherapy.

Though chemotherapy is an effective way to treat early-stage breast cancer, it also carries a risk of side effects. There is a delicate balance between the benefits of chemotherapy and the harm of possible side effects, said Canlan Sun, M.D., Ph.D., senior author of the study and associate research professor in the Department of Supportive Care Medicine at City of Hope.

The development of severe chemotherapy toxicity not only can harm the patient, but it can also compromise an older adults ability to complete the full course of chemotherapy, possibly reducing the potential benefit of the cancer treatment, she added.

Sedrak noted that most women with early stage breast cancer have a potentially curable disease and some would benefit from chemotherapy after surgery. Unfortunately, older adults aged 65 and over, who comprise about half of all breast cancer diagnoses, are significantly less likely to be offered chemotherapy compared to younger patients sometimes because their doctors fear they wont be able to tolerate it, he said. Older adults are also underrepresented in cancer trials, and we know little about how best to treat this heterogenous group.

The CARG-BC score is derived by combining eight disease and patient-reported predictors: use of an anthracycline chemotherapy, Stage 2 or 3 breast cancer, longer planned treatment duration, abnormal liver function, low hemoglobin, falls, limited walking ability and lack of social support.

This risk prediction model is an extension of prior work from the national Cancer and Aging Research Group led by scientists at City of Hope and elsewhere. As a National Cancer Institute-designated comprehensive cancer center, City of Hope offers integrated, multidisciplinary care that includes supportive care services addressing physical and emotional issues that can arise during and after treatment.

The newly developed CARG-BC score outperformed existing measures of patient performance status that are widely used in oncology such as the Karnofsky performance status or Eastern Cooperative Oncology Group performance status, both of which were developed and validated in younger patients.

Those clinician-based eyeball tests are imprecise and subjective, Sedrak said. They do not detect important factors such as functional reserve or the ability to respond to stress, which vary greatly between older patients of the same chronological age and are valued by patients and caregivers.

As a next step, the researchers will look to improve the chemotherapy toxicity risk assessment tool with more biological markers. They will attempt to identify biomarkers that could predict severe or deadly side effects to chemotherapy. They are working to identify interventions to support elderly breast cancer patients so that they derive the most benefit and the least toxicity from chemotherapy.

The researchers will also continue their efforts to improve access to cancer clinical trials for all patients, leveraging new innovations in technology and widely used social media networks.

The title of the study is Development and validation of a risk tool for predicting severe toxicity in older adults receiving chemotherapy for early-stage breast cancer (https://doi.org/10.1200/JCO.20.02063). It was supported by the National Institute on Aging (NIA R01 AG037037, K76 AG064394, K23AG038361, K24 AG055693, K24 AG056589), National Cancer Institute (K12CA001727, K12CA167540), National Institutes of Health (R21 AG059206), Breast Cancer Research Foundation, Susan G. Komen for the Cure (CCR14298143), American Cancer Society (125912-MRSG-14-240-01-CPPB) and Center for Cancer and Aging Research at City of Hope.

This research would not have been possible without the foundational scientific contributions made by the late Arti Hurria, M.D., former director of City of Hopes Center for Cancer and Aging Research.

About City of Hope

City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hopes translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin, monoclonal antibodies, and numerous breakthrough cancer drugs are based on technology developed at the institution. AccessHope, a wholly owned subsidiary, was launched in 2019 and is dedicated to serving employers and their health care partners by providing access to City of Hopes exceptional cancer expertise. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked among the nations Best Hospitals in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California and in Arizona. For more information about City of Hope, follow us on Facebook, Twitter, YouTube or Instagram.

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Vaccines at the Dinner Table – Psychiatric Times

I replied, Well, they showed that individuals who received the active vaccine injection were much less likely to get the infection than those who got a placebo or dummy injection without active vaccine.

She listened intently with a slightly worried expression.

But to make the study completely objective, it was double-blind, I said.

Whats that? she asked.

Double-blind means that both sides are blind or not given information about who got the real vaccine or placebo, I replied. Not the clinical team with the doctor, nurse, and other research staff on one side, and the patient and family and friends on the other side. No one directly involved with the patient in the study is allowed to know.

Her reaction was spontaneous and swift: But thats against human nature! How can we prevented from knowing if we are getting the real vaccine?

As a researcher, I have conducted many clinical trials with patients who express concern about the possibility of receiving a placebo, or find it hard to comprehend the restrictive rules of a double-blind design. These are counterintuitive methods, though required by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA), and other agencies worldwide. They are intended to increase objectivity because there is ample evidence that a positive bias naturally occurs in most patients and clinicians involved in a study.They expect the vaccine to be safe and effective, and their expectation often has a healing power of its own.

A long history confirms the need for research objectivity. Until the 18th century, average human longevity ranged from 30 to 50 years; it barely budged despite the thousands of new therapies pursued across the world, some based on ancient texts from a variety of cultures. But scientific proof was gradually replacing beliefs. Revolutionary advances like the discovery of antibiotics in the mid-20th century transformed human survival. Experimental methods to improve the accuracy of research findings, including the objective methods used routinely nowadays in clinical studies, were codified by scientists in the 20th century. During the last 2 centuries, the average human lifespan nearly doubledto over 75 years. The FDA adopted scientific methods by requiring that research studies in humans be conducted in phases. Phase 1 involves small-scale studies to determine safety, and at different doses, phase 2 involves mid-sized, double-blind studies with a placebo group to obtain initial information on efficacy and safety of the optimal doses identified in phase 1, and phase 3 requires large-scale, double-blind clinical trials with placebo built upon results from phases 1 and 2. If phase 3 results are positive, with sufficient safety and efficacy, the vaccine or drug is approved. But the work is not done. Phase 4 then begins with post-approval monitoring of side and adverse effects in those receiving the approved treatment or vaccine in standard clinical care.

Why are there so many hurdles to cross before approval, and more afterwards? Less than 1 in every 100 potential treatments makes it all the way from the basic science laboratory through clinical trials and finally regulatory approval for patient care. In other words, if we did not have the current regulatory system, tens of thousands of new vaccines, drugs and medical devices would be used widely, despite over 99% of them not meeting necessary standards of safety and efficacy. That would be like throwing us back to the healthcare standards of medieval and even earlier times.

My experience during the early days of the COVID-19 pandemic highlights the struggle to balance scientific knowledge with private beliefs and intrinsic daily habits. In late February 2020, I acquired N-95 masks and face-shields from our hospitals central supply and instructed all my clinical research staff to wear the mask and face-shield when seeing patients. In March 2020, just before the lockdown, we saw our last outpatient, who subsequently was hospitalized a few days later with COVID-19. I did not become ill but a few of my research staff members did, fortunately only with moderate symptoms that resolved in several weeks. Judging by when they became ill, they probably got the infection from that patient. When I asked, they told me that they had not worn the mask and face-shield continuously, as I had instructed. These team members routinely follow my instructions in carrying out their daily work but wearing a mask and face-shield went against their usual habits and beliefs.

If this was happening in a healthcare setting, the problems that we have seen with the publics response to the pandemic should not come as a surprise. To ensure a robust pandemic response in 2021, we all will need to better understand why so many people do not act in their own interest, and that of others. Public education about the science and the studies that produced FDA approval is essential, as is modeling by trustworthy, influential and diverse people doing the right thing.

But will that be enough? What do we need to know about those individuals (and groups) who demonstrate vaccine hesitancy, as has been abundant in refusals of flu and even measles vaccinations? The beliefs that underlie vaccine hesitancy may seem counter-intuitive, but they are prevalent and constitute a danger to that individuals health and to that of others. These actions may seem to go against the self-protective and social compact in human nature, except that it is other aspects of human nature, instinctive fear of the new and unknown as well as entrenched beliefs and habits, that are driving them. Let us hope it does not take centuries to understand what is going on and what works to alter vaccine hesitancy. We do not have the time for that.

Dr Devanand is professor of Psychiatry and Neurology and Director of Geriatric Psychiatry, Columbia University Irving Medical Center.

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The 17 Best Longevity Tips Experts Taught Us in 2020 – Well+Good

In recent years, the motivation for healthy habits like veggie-heavy diets and regular exercise has shifted from present-day benefits to those more long-term in nature. And were not just interested in extending our lifespan, but our health span, tooaka the length of time we are not only alive but alive and well. Most of us want to die with our boots on, as my grandfather would sayable in both mind and body.

As such, longevity research has become a major focus in the wellness world and this year, we learned quite a bit about how to optimize our daily lives now for the benefit of our future selves. Below, a rundown of the best tips weve accumulated in 2020 for living your healthiest life into your 80s and beyondbecause theres a lot to live well for just ask President-Elect Joe Biden, who is 78!

1. Exercise this many times per week

Its no secret that human beings were designed to be a lot more active than most of us currently are in our modern-day, screen-heavy existences; however, you dont need to give up hope of a long life if youre pressed for tons of time to move each week. This year, a new study published inJAMA Internal Medicinefound that those who engage in moderate or vigorous exercise 150 minutes per weekhad lower all-cause mortality.

That translates to just 22 minutes of moderate-to-intense exercise per day. Those who got these 150 minutes per week showed a lower risk of early death from all-cause mortality, cardiovascular disease mortality, and cancer mortality.

Benefits were especially notable in those who tended toward the more rigorous side of the equation, opting for running, High Intensity Interval Training (HIIT) routines, or something equally as taxing. The takeaway there is that if you are doing lower-impact exercises, it might help to throw a few more hardcore (think: quick and dirty) fitness routines into the mix as well. Not sure where to start? Here are nine such workouts you can try now (or January 1, because resolutions).

2. This particular workout format packs the best longevity punch

Any exercise is better than none, so if theres a format you love and that gets you moving, you should one hundred percent stick to it. But if youre open to new things or are already a devotee, research this year shows that HIIT workouts are the most effective form of fitness from a longevity standpoint.

The study looked at the effects of two weekly HIIT workouts per week on 70 to 77 year-olds and found that all-cause mortality was 36 percent lower in that group than in the studys control group (which did whatever kind of exercise they liked). Thirty-six percent!

The specific HIIT routine the studys participants engaged in was the 44 format, which divides each workout into a 10-minute warm-up period followed by four high-intensity intervals. Each interval consists of one to two minutes of extreme exertion, at about 90 percent of maximum heart rate, followed by a three-minute period at about 60 percent of heart rate. The session then concludes with a cool down period. If you want toe try one out, here are four to get you started.

3. If your workouts dont include this one move, they probably should

Technically, research just shows that if you can do this one move easily, that in and of itself is a good indication of longevity: the squat. So while this doesnt necessarily show that doing squats will increase your lifespan, it stands to reason that one way to ensure you can do them easily is to, well, do themand frequently.

One of the reasons its such a good exerciseboth to practice frequently and as a longevity predictor is that its functional, meaning we sort of need to be able to execute squat-like movements regularly in everyday life when, for example, we move from sitting to standing. Plus, we sit too much, and therefore the parts of our bodies, e.g. the glutes, which squats activate do not get nearly the amount of work they were built to take on.

Its critical, howeverfor knee health especiallythat you squat with proper form; heres how.

4. Cardio is not to be overlooked, either

Its not always possible for everyone to engage in high-impact exercise like HIIT or running, but that doesnt mean theyre screwed from a longevity perspective. In some cases, people might want to choose exercises that are gentler on their joints, which is not the same thing as being easy.

According to a cardiologist, there are five types of low-impact cardio thatll work you out hard without irritating aging or injured parts of your body: swimming, walking, cycling, rowing, and elliptical. Or, heres a 25-minute low-impact cardio workout you can try from home today.

5. Overall, your workout routines should include these 3 pillars

Ultimately, the best fitness routines are a mix of a number of different modalities, and exercising for longevity is no different. According toAleksandra Stacha-Fleming, founder of NYCs Longevity Lab, a gym that works with people of all ages to create workouts that help their bodies age properly, your regular workouts should typically include a smattering of the following: cardio, for your heart; strength-training, for your bones; and anything that works your flexibility and mobility, e.g. yoga. Get workout vids for each here.

1. Always keep these 6 foods on hand in your fridge

According to Dan Buettner, longevity expert and author ofThe Blue Zones Kitchen, the longest-living people in the world dont obsess over or restrict what they eat; however, they naturally consume nutrient-dense foods as a way of life. The six such foods Buettner thinks you should stock up on ASAP to follow their lead are nuts, vegetables, fruit, tofu, fish, and alt-milk. Find out more about why here.

You might want to add a jar of canned hearts of palm to your shopping list the next time youre try to stock your fridge, too. The ingredient is nutrient-dense, antioxidant-rich, and packed with minerals like potassium, iron, phosphorus, and zinc. Most importantly, its Blue Zones diet-approved, meaning its a longevity-booster, too. Try these 9 recipes to make use of your next hearts of palm haul.

2. Meanwhile, these 5 foods should go in your freezer

Buettner also has thoughts on what should be found in your freezer if you hope to emulate the worlds centenarians. His top five picks include a lot of the same things you should simultaneously keep fresh in your fridge, like fruits and vegetables, and nuts fall into both categories, too. Additionally, Buettner recommends keeping bread (bless you, Buettner!) and whole grains on ice, too. Get a few recipes made with each ingredient on this Buettners freezer list here.

3. Pack these in your pantry

Buettner even shared what he keeps in his own kitchen specifically when it comes to his pantry. What youll find there includes staples such as beans, legumes, whole grains (specifically steel-cut oats and brown rice), nuts, and seeds. You should keep canned greens in your pantry, too.

4. Herbs and spices are oh-so-important, too

Excess inflammation is an enemy of healthy aging, and plants are packed with anti-inflammatory and antioxidant properties. According to herbalist Rachelle Robinett, nutrient-dense herbs are, therefore, a great supplement for anyone looking to enhance the longevity benefits of their diet. Specifically, she recommends ginger, turmeric, spirulina, chili peppers, and ginsengfind out more on why here.

People in the Blue Zone of Okinawa, Japan, also consume an herb called otani-watari, which can be boiled and added to stir-fries, soups, and salad.

4. This one-pot recipe is a longevity experts favorite go-to meal

Whatever Buettner, whos made his lifes work longevity, is eating regularly, Ill have, too. Fortunately, this year he shared his favorite go-to meal, which just so happens to be a one-pot Ikarian Longevity Stew packed with legumes and superstar veggies. Get the recipe here.

5. Overall, its this popular diet that wins the day with respect to longevity

You may have noticed a theme in the above tips, which is that they heavily emphasize fruits, vegetables, nuts, legumes, and whole grains; however, the longest-living people in the world arent necessarily vegans. Instead, they adhere to the Mediterranean Diet, and recent research has strengthened the link between it and longevity.

The study found that the Mediterranean diet may be linked to lowering inflammation markers and increasing both brain function and gut healthand therefore improving the aging process overall.

Essentially, the Mediterranean diet does call for substantial amounts of those aforementioned fruits, veggies, whole grains, and nuts. It also adds olive oil as a key component alongside fish and encourages a reduction in the consumption of red meat and saturated fats.

Need a little help making shifting your eating habits to better reflect this diet? Try the Blue Zones specific daily, weekly, and monthly guide for eating more like the longest-living humans on the planet.

6. To keep it simpler still, follow these golden rules of eating for longevity

If all of the above sounds like a lot, consider this; according to Buettner, there are six golden consumption rules to follow if you want to live longer, and TBH, theyre not very restrictive. The first is to drink wine after 5 p.m., ideally with friends or loved ones and a meal. (Um, twist my arm!) The second is to eat mostly plant-based foods, which at this point feels a bit repetitive, so duh. The third is to forget fad-diet brainwashing and carbo load to your hearts desire, as long as your carbs of choice are derived from grains, greens, tubers, nuts, and beans. The fourth is to eat less meat, as mentioned prior, and the fifth is to stick to just three beveragescoffee, that aforementioned wine (okay, yes), and lots and lots of water. Find out what the lastand least obviousgolden rule is here.

1. Keep a consistent sleep schedule

The Dalai Lama might not be a longevity expert per se, but he is doing pretty well at the spritely age of 85. One of his top six tips for extending your lifespan is to maintain a consistent sleep schedule. And even though he starts his day at 3 a.m., his 7 p.m. bedtime ensures he gets a solid eight hours of sleep per night.

Hobbies

1. Volunteer

One less-easy-to-imitate characteristic of those occupying the worlds Blue Zones is that they retain a sense of purpose throughout their lives. In America, we tend to put older people to pasture, so to speak, and they are less naturally integrated into family and community life, too.

One way to hack a sense of purpose in our (cold, heartless) societynot just when youre older but at any ageis to volunteer. Research shows that helping other people can actually help you to live a longer life. Our results show that volunteerism among older adults doesnt just strengthen communities, but enriches our own lives by strengthening our bonds to others, helping us feel a sense of purpose and well-being, and protecting us from feelings of loneliness, depression, and hopelessness, Eric S. Kim, PhD, research scientist at the Harvard T.H. Chan School of Public Health, said in a press release about the study. Find out more here, including how to adapt this hashtag-goals habit to pandemic times.

2. Grow a green thumb

According to Buettner, people in the Blue Zones, or longest-living areas of the world, garden well into their 90s and beyond. Gardening is the epitome of a Blue Zone activity because its sort of a nudge: You plant the seeds and youre going to be nudged in the next three to four months to water it, weed it, harvest it, he says. And when youre done, youre going to eat an organic vegetable, which you presumably like because you planted it. Find out more on the research behind this here.

3. Meditate

Not to state the obvious, but the Dalai Lamas longevity routine also includes regular meditation. And while he practices for seven hours a day, research shows that just five minutes per day can reap benefits such as sharpening your mind, reducing stress and, importantly, slowing aging.

4. Practice compassion

The Dalai Lama considers compassion to be one of the keys to happiness, and science says it has pro-social benefits, too. These might help us live longer lives, as humans thrive in the communities many Americans find it more difficult to build than those living in the Blue Zones do. Showing concern, care, and empathy to others can endear you to them and ensure that when the shoe is on the other foot, youve got others to lean on, too. This reciprocal relationship gives you that aforementioned sense of longevity-endowing purpose, too.

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Reversing The Aging Clock With Epigenetic Reprogramming – Bio-IT World

By Deborah Borfitz

January 13, 2021 | As aging researchers are aware, birthday candles are not a good guide to either human health or longevity. But there is an abundance of clues in the genome and, as suggested by studies in animals, some of age-related damage is reversible by removing or reprogramming problematic cells or blocking the activity of key proteins.

As it turns out, DNA methylationa frequently-used biomarker of biological ageis not just marking time like a clock on the wall but actually controlling time within cells, according to David Sinclair, an expert on aging at Harvard Medical School and cofounder of 4-year-old Life Biosciences. The revelation emerged from a study recently published in Nature (DOI: 10.1038/s41586-020-2975-4) where Harvard researchers showed, for the first time, that the pattern of DNA methylation in the genome can be safely reset to a younger age.

It was in fact a prerequisite to restoring youthful function and vision in old mice, says Sinclair, who has spent most of his adult life studying the epigenetic changes associated with aging. Up until a few years ago, he thought the process was unidirectional and that cells ultimately lost their identity and malfunctioned or became cancerous.

It seemed crazy to try to get proteins to return to the place they were in young cells, Sinclair says. Proteins move around in response to age-associated DNA damage and end up in the wrong places on the genome, causing the wrong genes to be turned on, but scientists did not know if proteins could go back, where the instructions were stored, or if they were being stored at all.

As covered in his 2019 bestseller Lifespan, Sinclair now believes that aging is the result of the so-called epigenetic changes scrambling how the body reads genetic code. Were essentially looking for the polish to get the cell to read the genome correctly again, he says, a process he likens to recovering music on a scratched CD.

Yamanaka Factors

Sinclair and his research associates have been focusing on the eye, in part because retinal tissues start aging soon after birth, he explains. While a damaged optic nerve can heal in a newborn, the injury is irreversible in a 1-year-old.

Yuancheng Lu, a former student of Sinclairs, was also interested in the eye because his family has a vision-correction business and recognized sight loss as a huge unmet need, he continues. We thought if we could take the age of those retinal cells back far enough, but not so far that they lose their identity, we might be able to see regrowth of the optic nerve if it was damaged.

Among the foundational work was a 2016 study in Cell (DOI: 10.1016/j.cell.2016.11.052) by Life Biosciences cofounder Juan Carlos Izpisua Belmonte (Salk Institute for Biological Studies) who partially erased cellular markers of aging in mice that aged prematurely, as well as in human cells, by turning on Yamanaka factors Oct4, Sox2, Klf4, and c-Myc (OSKM) highly expressed in embryonic stem cells. Short-term induction of OSKM ameliorated hallmarks of aging and modestly extended lifespan in the short-lived mice.

The lifespan gain was widely dismissed as an artifact of shocking a mouse, says Sinclair, since the mice died if the treatment continued for more than two days. Although the human health implications appeared unlikely, his Harvard team decided to try the approach using an adeno-associated virus as a vehicle to deliver the youth-restoring OSKM genes into the retinas of aging mice.

The technology kept killing the mice or causing them to get cancer until Lu decided to drop the c-Myc genean oncogenein his experiments using human skin cells. He looked at [damaged] cells that had been expressing OSK for three weeks and the nerves were growing back toward the brain to an unprecedented degree. Moreover, the cells got older by the damage and younger by the treatment.

As the broader team went on to show in the Nature paper, the trio of Yamanaka factors effectively made cells younger without causing them to lose their identity (i.e., turning back into induced pluripotent stem cells) or fueling tumor growth even after a year of continuous treatment of the entire body of a mouse. If anything, the mice had fewer tumors over the course of the study, says Sinclair.

Although the mice needed to be autopsied to definitively measure tumor burden, Sinclair says the study will be repeated to learn if the epigenetic reprogramming technique can increase lifespan.

Findings have implications beyond the treatment of age-related diseases specific to the eye, says Sinclair. Aging researchers have published studies showing other types of tissues, including muscle and kidney cells, can also be rejuvenated.

Clocked Results

In the latest study using mice, epigenetic reprogramming was found to have three beneficial effects on the eye: promotion of optic nerve regeneration, reversal of vision loss with a condition mimicking human glaucoma, and reversal of vision loss in aging animals without glaucoma. The latter finding, from Sinclairs vantage point, is the most important one. This is ultimately a story about finding a repository of youthful information in old cells that can reverse aging.

Results of all three experiments are noteworthy and have commonly thought to be three separate processes, says Sinclair. That is only because the fields of aging and acute and chronic disease are distinct disciplines that rarely talk to each other.

The Harvard team is pioneering a new way to tackle diseases of aging by addressing the underlying cause. This is the first time, as far as Sinclair is aware, where nerve damage was studied in old rather than young animals. In the case of glaucoma and most diseases, aging is considered largely irrelevant, when of course we know glaucoma is a disease of aging.

A variety of aging clocks, including some the research team built themselves, have been deployed for studies because they are considered the most accurate predictor of biological age and future health, says Sinclair. As embryos, cells lay down different patterns of methylation to ensure they remember their purpose over the next 80 to 100 years.

For unknown reasons, methyl groups get predictably added and subtracted from DNA bases across cell and tissue types and even species, Sinclair says. In 2013, UCLAs Steve Horvath (another Life Biosciences cofounder) showed that machine learning could be used to pick out the hot spots and predict individual lifespan depending on how far above or below the DNA methylation line they sit (Genome Biology, DOI: 10.1186/gb-2013-14-10-r115).

A multitude of aging clocks have since been developed. Eventually, we will need some standardization in the field, but there is nothing super-mysterious about aging clocks, says Sinclair. One of my grad students could probably get you one by the end of the day.

Booming Field

Aging research is a rapidly accelerating field and epigenetic reprogramming is poised to become a particularly active area of inquiry. In terms of numbers, there are still only a dozen or so labs intensely working on this, but there are probably a hundred others I am aware of who are getting into it, says Sinclair.

Life Biosciences began with four labs, but new ones are now joining on an almost weekly basis, he adds. Collaborators have expanded work to the ear and other areas of the body beyond the eye, he adds.

Were also reducing the cost of the DNA clock test by orders of magnitude so [biological age prediction] can be done on millions of people, he continues. In the future, aging clocks are expected to be a routine test in physicians arsenal to guide patient care as well as to monitor response to cancer treatment.

Harvard University has already licensed two patents related to the technology used by the aging researchers to Life Biosciences, Sinclair says. The company has built a scientific team with a group of world-class advisors who developed gene therapy for the eye, which will be tested first for the treatment of glaucoma.

The role of chaperone-mediated autophagy in aging and age-related diseases is another promising area of research being pursued by Life Biosciences Ana Maria Cuervo, M.D, Ph.D., professor, and co-director of the Institute of Aging Studies at the Albert Einstein College of Medicine. Cuervo recently reported at a meeting that fasting-induced autophagy, the cells natural mechanism for removes unnecessary or dysfunctional components, can greatly extend the lifespan of mice. She believes the triggering of this process might one day help treat diseases such as macular degeneration and Alzheimers.

The specialty of Manuel Serrano, Ph.D., the fourth company cofounder, is cellular senescence and reprogramming and how they relate to degenerative diseases of the lung, kidney, and heart. He isan internationally recognized scientist who has made significant contributions to cancer and aging research and works in the Institute for Research Biomedicine in Barcelona.

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Post-Surgical Patch Releases Non-Opioid Painkiller Directly to the Wound – Duke Today

DURHAM, N.C. A Duke-led team of scientists has developed a bio-compatible surgical patch that releases non-opioid painkillers directly to the site of a wound for days and then dissolves away.

The polymer patch provides a controlled release of a drug that blocks the enzyme COX-2 (cyclooxygenase-2,) which drives pain and inflammation. The study appears Jan. 10, 2021 in the Journal of Controlled Release.

When they started We were making hernia meshes and different antimicrobial films, said Matthew Becker, the Hugo L. Blomquist professor chemistry at Duke, and last author on the paper. We thought you could potentially put pain drugs or anesthetics in the film if you just sew it in as you're stitching the person up, then you wouldn't necessarily have to prescribe any opioids, Becker said.

The work grew out of a $2 million grant Becker received from the state of Ohio at his previous institution to investigate non-opioid pain management , one measure toward fighting a nationwide epidemic of opioid drug abuse. Since arriving at Duke in 2019, Beckers team has partnered with Duke pain control expert Dr. Ru-Rong Ji and his team to refine the idea.

The polymer itself, comprised of poly(ester urea) homopolymers and co-polymers, is also special, said Becker, who is also a professor of mechanical engineering and materials science in Duke's Pratt School of Engineering.

Most polymers that are used in medicine swell, and everything comes out at once, Becker said. But this polymer erodes slowly, and its painkiller dose and longevity can be controlled simply by varying the surface area and thicknesses. The film is about like a piece of paper.

If you can get four or five days of pain control out of the patch and not have to take those other pain drugs, not only do you avoid some of the side effects and risks of addiction, youre concentrating therapy where you need it, Becker said.

Rat studies also showed that the painkiller stayed in tissues close to the patch site, rather than dissolving into circulating plasma.

Becker said the patch should be able to provide three or four days of wound-pain management, which is the critical period for post-surgical pain. The implantable film would be particularly useful in endoscopic procedures and instances where the physicians and patients would like to avoid opioid exposure such as Cesarean births and pediatric surgeries. In studies with mice that mimic the neuropathic pain of diabetes, the pain patch was placed against a nerve and provided a four-day nerve block.

This research was sponsored by Merck Sharp & Dohme Corp, 21st Century Medical Technologies and the Ohio Third Frontier Opioid Challenge. Becker and co-author Natasha Brigham have filed provisional patent applications with the University of Akron Research Foundation. Becker also is a board member and equity holder in 21st Century Medical Technologies.

CITATION: Controlled Release of Etoricoxib from Poly(ester urea) Films for Post-Operative Pain Management, Natasha Brigham, Rebecca Nofsinger, Xin Luo, Nathan Dreger, Alexandra Abel, Tiffany Gustafson, Seth Forster, Andre Hermans, Ru-Rong Ji, Matthew Becker. Journal of Controlled Release, Jan. 10, 2021. DOI: 10.1016/j.jconrel.2020.11.052

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Post-Surgical Patch Releases Non-Opioid Painkiller Directly to the Wound - Duke Today

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P33 and Mayor Lori E. Lightfoot, Together With Joint Venture Team Kaleidoscope Health Ventures, Farpoint Development and Israel’s Sheba Medical…

CHICAGO, Jan. 14, 2021 /PRNewswire/ --Newsweek global top-10, Israel-based Sheba Medical Center, world-renowned for its innovation model known as ARC (Accelerate, Redesign, Collaborate), has signed an official deal led by Kaleidoscope Health Ventures. Sheba, together with Kaleidoscope and Farpoint Development, are entering a joint venture to develop, execute and lead the Chicago ARC Innovation Center based on a shared vision for the transformation of health care.

The JV unites the successful ARC open collaboration modela repeatable prototype that exemplifies Israel's "Startup Nation" mindsetwith a market-driven approach adapted for the U.S.The center will be an anchor for the $7 billion, 100-acre Bronzeville Lakefront development on the historic site of the Michael Reese Medical Center.

The Chicago ARC will give international companies a U.S. foothold, develop health disparity solutions, incubate health innovation startups, collaborate on data science initiatives and be a gateway for global investment.

Chicago ARC Innovation Center Is Unique, With Many Firsts

The Chicago ARC aims to create billions of dollars in value and dramatically accelerate the successful adoption and adaptation of disruptive technologies. Under the leadership of the JV team, the Chicago ARC will foster new capabilities that grow health ventures through access to data, experienced operators, customers and capital. Focus areas include precision medicine, big data and artificial intelligence, virtual reality, telehealth and medical technologies. The Chicago ARC model includes:

Chicago Is Ground Zero for Global Health Innovation

Illinois has all the ingredients to create better health outcomes. It is among the nation's top producers of STEM degrees and is home to the third largest medical and life science economic engine in the nation. World Business Chicago reported that the Chicago region generates approximately $72 billion in economic output and supports almost 700,000 employees annually. As one of only four U.S. cities with three tier-one research universities, Chicago area institutions amassed over $900 million in National Institutes of Health-funded research and development funding as of 2019.

"The Chicago ARCwill enhance our incredible reserve of STEM talent, expand our next generation life sciences ecosystem and attract further capital to accelerate growth, while also serving asa transformational epicenter geared toward creating healthcare equity across our city's South Side communities," Mayor Lori E. Lightfoot said.

"Given these assets, and the extensive preexisting global partnerships brought by ARC to Chicago, this new venture sets the stage for the development of a new global innovation model. It will be a model that fuels the kind of transformative and collaborative change every life sciences innovation hub should aim to createa model from the start that is focused on inclusion and designed to use assets across communities, states and countries," P33 CEO Brad Henderson said.

This announcement comes on the heels of recent announcements that demonstrate Chicago's goal, and ability, to become a global innovation destination. "We've already been recognized for our leadership in quantum science and in startup exit value," Henderson said. PitchBook just recognized Chicago as the top U.S. city for exit value fueled by VC investment in 2020.

"We're focused on building transformative partnerships that improve economic growth and equity in our city, and Sheba's first physical U.S. innovation center gives us a tremendous opportunity to further this goal. Given our depth of talent and entrepreneurial spirit, Chicago will be able to serve as the epicenter for their North American partnerships and help create a world class healthcare innovation hub," World Business Chicago Interim President & CEO Michael Fassnacht said."We welcome Chicago ARC's vision and the JV team's expertise in innovation and inclusivity to carry on the legacy of the formerMichael Reese Medical Center."

Healthcare Equity Is the Underlying Mission

"Our primary purpose goes beyond turning scientific discovery into financial returns; it's about turning scientific discovery into scalable innovation that drives health equity for all. The Chicago ARC redesigns the way healthcare innovation is done to achieve this commitment. It's an especially critical goal in Chicago because there's a 30-year life expectancy gap between the city's poorest and wealthiest ZIP codes," Kaleidoscope Co-founder S. Bob Chib noted.

"Tackling pressing health challenges through a collaborative platform will bring solutions to the market faster that not only generate significant financial returns but also enable health, social and economic justice throughout our state and nation," Kaleidoscope Co-founder Ken Bahk added.

"The Chicago ARC is an ideal catalyst for the Bronzeville Lakefront development, which we envision as a healthy neighborhood of the future. We plan to break ground in mid-2021. In the interim, the Chicago ARC will operate from a nearby space and move to the Bronzeville Lakefront site when the 500,000-square-foot facility is completed in Q4 2023," Farpoint Managing Principal Scott Goodman said.

"The Bronzeville community has been a center of medical innovation for more than 125 years. Dr. Daniel Hale Williams performed the first successful open-heart surgery here in 1893 at Provident Hospital, the nation's first nonsegregated hospital which he also founded in 1891. It's fitting that Sheba's ARC Innovation Center will anchor, with an equity lens, the anticipated Bronzeville Lakefront development on the former site ofthe historic Michael Reese Hospital. It will continue our community's consequential legacy in developing life science solutions with global impact," Alderman Sophia King (4th) said.

Israel and Sheba Are Committed

"The ARC Innovation Center aligns with one of Israel's greatest prioritiesthe transformation of health care. COVID-19 has reinforced how important it is to address and achieve health equity, making new and smarter healthcare approaches even more urgent and pressing," Sheba Deputy Director General, Chief Medical Officer and Chief Innovation Officer Dr. Eyal Zimlichman said.

"Transforming health requires more than a single institution or nation,which is why global collaboration is so important. Israel, and Sheba as its national medical center, started the journey long ago to disrupt health care through groundbreaking technology. TheChicago ARC Innovation Centerwill expand our efforts in the largest global market,"Sheba Director General Prof. Yitshak Kreiss added.

"With Sheba's expertise in healthcare innovation, the leadership of Chicago and a pioneering joint venture, this partnership will help drive health equity and economic growth throughout the entire city and beyond for decades," Chicago's Israeli Counsel General Aviv Ezra noted. "The Consulate's partnership with Kaleidoscope and this initiative has been one of our main focuses during my time as Consul General in Chicago. It's a win-win for everyone."

About the Chicago ARC Innovation Center Joint Venture Partners

Sheba, Kaleidoscope and Farpoint are partnering to realize a new model for holistic health, wellness and longevity by connecting the best science, talent, technology and data globally. The team has engineered the Bronzeville Lakefront planned development as an ESG-aligned health and wellness innovation hub to attract strategic partners and investors. The partners have proven track records in developing and executing notable projects and decades of successful leadership in their respective fields, as noted here:

About P33

About World Business Chicago

Contact:Kellie Quinn, [emailprotected]

SOURCE Kaleidoscope Health Ventures

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