Month: January 2019

Telomere extension turns back aging clock in cultured human cells, study finds.

Researchers delivered a modified RNA that encodes a telomere-extending protein to cultured human cells. Cell proliferation capacity was dramatically increased, yielding large numbers of cells for study.

A new procedure can quickly and efficiently increase the length of human telomeres, the protective caps on the ends of chromosomes that are linked to aging and disease, according to scientists at the Stanford University School of Medicine.

Treated cells behave as if they are much younger than untreated cells, multiplying with abandon in the laboratory dish rather than stagnating or dying.

The procedure, which involves the use of a modified type of RNA, will improve the ability of researchers to generate large numbers of cells for study or drug development, the scientists say. Skin cells with telomeres lengthened by the procedure were able to divide up to 40 more times than untreated cells. The research may point to new ways to treat diseases caused by shortened telomeres.

Telomeres are the protective caps on the ends of the strands of DNA called chromosomes, which house our genomes. In young humans, telomeres are about 8,000-10,000 nucleotides long. They shorten with each cell division, however, and when they reach a critical length the cell stops dividing or dies. This internal “clock” makes it difficult to keep most cells growing in a laboratory for more than a few cell doublings.

‘Turning back the internal clock’

“Now we have found a way to lengthen human telomeres by as much as 1,000 nucleotides, turning back the internal clock in these cells by the equivalent of many years of human life,” said Helen Blau, PhD, professor of microbiology and immunology at Stanford and director of the university’s Baxter Laboratory for Stem Cell Biology. “This greatly increases the number of cells available for studies such as drug testing or disease modeling.”

A paper describing the research was published today in the FASEB Journal. Blau, who also holds the Donald E. and Delia B. Baxter Professorship, is the senior author. Postdoctoral scholar John Ramunas, PhD, of Stanford shares lead authorship with Eduard Yakubov, PhD, of the Houston Methodist Research Institute.

The researchers used modified messenger RNA to extend the telomeres. RNA carries instructions from genes in the DNA to the cell’s protein-making factories. The RNA used in this experiment contained the coding sequence for TERT, the active component of a naturally occurring enzyme called telomerase. Telomerase is expressed by stem cells, including those that give rise to sperm and egg cells, to ensure that the telomeres of these cells stay in tip-top shape for the next generation. Most other types of cells, however, express very low levels of telomerase.

Transient effect an advantage

The newly developed technique has an important advantage over other potential methods: It’s temporary. The modified RNA is designed to reduce the cell’s immune response to the treatment and allow the TERT-encoding message to stick around a bit longer than an unmodified message would. But it dissipates and is gone within about 48 hours. After that time, the newly lengthened telomeres begin to progressively shorten again with each cell division.

The transient effect is somewhat like tapping the gas pedal in one of a fleet of cars coasting slowly to a stop. The car with the extra surge of energy will go farther than its peers, but it will still come to an eventual halt when its forward momentum is spent. On a biological level, this means the treated cells don’t go on to divide indefinitely, which would make them too dangerous to use as a potential therapy in humans because of the risk of cancer.

          This new approach paves the way toward preventing or treating diseases of aging.

The researchers found that as few as three applications of the modified RNA over a period of a few days could significantly increase the length of the telomeres in cultured human muscle and skin cells. A 1,000-nucleotide addition represents a more than 10 percent increase in the length of the telomeres. These cells divided many more times in the culture dish than did untreated cells: about 28 more times for the skin cells, and about three more times for the muscle cells.

“We were surprised and pleased that modified TERT mRNA worked, because TERT is highly regulated and must bind to another component of telomerase,” said Ramunas. “Previous attempts to deliver mRNA-encoding TERT caused an immune response against telomerase, which could be deleterious. In contrast, our technique is nonimmunogenic. Existing transient methods of extending telomeres act slowly, whereas our method acts over just a few days to reverse telomere shortening that occurs over more than a decade of normal aging. This suggests that a treatment using our method could be brief and infrequent.”

Potential uses for therapy

“This new approach paves the way toward preventing or treating diseases of aging,” said Blau. “There are also highly debilitating genetic diseases associated with telomere shortening that could benefit from such a potential treatment.”

Blau and her colleagues became interested in telomeres when previous work in her lab showed that the muscle stem cells of boys with Duchenne muscular dystrophy had telomeres that were much shorter than those of boys without the disease. This finding not only has implications for understanding how the cells function — or don’t function — in making new muscle, but it also helps explain the limited ability to grow affected cells in the laboratory for study.

The researchers are now testing their new technique in other types of cells.

“This study is a first step toward the development of telomere extension to improve cell therapies and to possibly treat disorders of accelerated aging in humans,” said John Cooke, MD, PhD. Cooke, a co-author of the study, formerly was a professor of cardiovascular medicine at Stanford. He is now chair of cardiovascular sciences at the Houston Methodist Research Institute.

“We’re working to understand more about the differences among cell types, and how we can overcome those differences to allow this approach to be more universally useful,” said Blau, who also is a member of the Stanford Institute for Stem Cell Biology and Regenerative Medicine.

“One day it may be possible to target muscle stem cells in a patient with Duchenne muscular dystrophy, for example, to extend their telomeres. There are also implications for treating conditions of aging, such as diabetes and heart disease. This has really opened the doors to consider all types of potential uses of this therapy.”

References 

Krista Conger, Stanford co-authors – Jennifer Brady, PhD, and Moritz Brandt, MD; senior research scientist Stéphane Corbel, PhD; research associate Colin Holbrook; and Juan Santiago, PhD, professor of mechanical engineering.

This work was supported by the National Institutes of Health (grants R01AR063963, U01HL100397 U01HL099997 and AG044815), Germany’s Federal Ministry of Education and Research, Stanford Bio-X and the Baxter Foundation.

Ramunas, Yakubov, Cooke and Blau are inventors on patents for the use of modified RNA for telomere extension.

Gerald J. Joseph HealthCoach 2019

The “Unclogging” of Healthcare Delivery

January 2019

HealthCoach- Corporate Wellness  

 

A well-crafted Corporate Wellness Program adapts easily to the digital world of smartphone messaging, wearable biometric data, content delivery and modern wellness strategies.

As we move deeper into the 21st century of healthcare delivery, it has become readily apparent that the epidemic of chronic disease will remain the primary focus of most reform measures by necessity. The United States currently spends 18% of its GDP on healthcare (4,13) and at least 70% of these costs are related to the management of preventable chronic health conditions (6). These costs are projected to double every 25 years, reaching 34% by 2040, and are largely felt to be unsustainable. To respond to this crisis, the United States enacted the Affordable Care Act which seeks to incentivize improved health at a reduced cost through the use of “Big Data” to identify modifiable risk factors in a given population. The “Big Data” approach to achieving cost-effective outcomes is being used in most other industries and healthcare has finally caught on to its potential value.

According to the World Health Organization, 80% of heart disease, stroke, and type 2 diabetes could be prevented and 40% of cancer could be prevented (1). These are the major conditions that are driving increased healthcare costs within the United States. In order to harness the tremendous opportunity to save money by preventing these conditions even before symptoms have appeared, providers will need to shift resources away from costly and risky medical services to less costly and safer preventive services. The United States currently spends 96% on medical services and only 4% on prevention (6).

The United States currently spends 96% on medical services and only 4% on prevention

The Centers for Disease Control reports that the leading drivers of death and disability mostly related to these chronic conditions are poor diet, reduced physical activity, and cigarette smoking. Even though this information has been widely disseminated, less than 3% of the public is following all of the CDC’s recommendations for living a healthy lifestyle (25) and less then 50% are adhering to their medication prescriptions written mostly to stabilize the effects of these lifestyle “risk factors” (37).

This lack of adherence to lifestyle recommendations and to medication prescriptions has resulted in poor control of disease precursors like blood lipids, blood pressure, and blood sugar (targets are being met <50% of the time, 36).

To better understand why lifestyle factors are so important for health, research anthropologists report (21, 20) that the human genetic make-up has changed little in the past 40,000 years and that modern humans are genetically best adapted to:

• Eat natural foods from the earth
• Live outdoors with moderate exposure to the sun
• Live among others in supportive groups
• Sleep when the sun goes down and awaken as the sun comes up
• Walk 5-10 miles each day
• Exhibit a stress response to short-lived stressors and then return to relaxation

They point out that there is a mismatch between how our ancestors lived for 2.5 million years and how we began living only 10,000 years ago after the agricultural revolution (farming, domesticated animals, grains, dairy) and 200 years ago after the industrial revolution (cities, indoor living, decreased family support, decreased physical activity). These mismatches have increased dramatically in the past 30 years:

• Sugar consumption has increased from about 2 pounds per person per year at the beginning of the 20th century to about 150 pounds today (7)
• Processed foods made from refined sugars, cereals, refined vegetable oil, alcohol and dairy products has reached 72% of adult calorie intake (2)
• 79.4% of Americans are physically inactive (3)
• Vitamin D deficiency predominantly from lack of sunlight exposure has reached 82% in some populations (23)
• 18.2 % of the population continues to smoke (6, 3)
• 17.4% of youths age 12-17 use either alcohol or drugs (6, 3)

The best evidence tells us that these mismatches are major contributors to the onset of type 2 diabetes, heart disease, stroke, cancer, Alzheimer’s disease, liver and kidney disease, depression, falls, disability and death (6,1,3,8,9,14,22). These conditions account for most of the chronic disease burden seen around the world and data from the CDC reveals that genetic make-up contributes only 15-18% to the causes of these conditions. The other 80-85% consists of health behaviors, psychosocial factors, and environmental exposures (6, 1).

Our current healthcare system has focused resources mostly on providing care after symptoms, disease, and disability have appeared, instead of focusing on prevention (1,6,19,20,1,11). Healthcare payments tied to fee for service have incentivized care delivery to provide services after blood vessels have become “clogged” (diabetes, coronary heart disease), joints have become arthritic (osteoarthritis, rheumatoid arthritis, lower back pain), and organs have become impaired (cirrhosis, Alzheimer’s disease, kidney failure). Each year in the United States, 2.4 million angiograms, 1 million knee and hip replacements, and 51.4 million medical procedures are carried out (6).

To further frame the problem in the United States:

• We spend 2 ½ times more then the average of our peer nations on healthcare per capita per year (25)
• We rank 37^th in overall population health compared to our peer nations (8)
• 77% of those over age 65 have either pre-diabetes or diabetes (9)
• Diabetes accounts for >20% of healthcare costs (9)
• Diabetic patients cost 2.3 times more then non-diabetics each year on average for healthcare (9)
• We rank #1 in the world in prescription drug use (5)
• 76% of every clinical encounter in the U.S. involves a medication (28)
• 80% of the worlds opiate pain pills are prescribed in the United States (27)
• 70% of Americans take one medication, 50% take two, and 20% take five. (26)
• 1/3 of older adults over age 65 fall each year and that increases to 50% for those over age 80 (6)

Now more then ever, we can’t afford to wait for symptoms, disease, or disability to occur before we actively and continuously engage patients in the work of self-care. We need to implement a prevention and wellness delivery system that supports patients in the work of building resiliency by self-managing conditions and lifestyle particularly in between acute episodes of care.

We can’t afford to wait for symptoms, disease, or disability to occur

Our emphasis on pharmaceutical and medical service prescription for chronic disease is unsustainable and has to change if we are to have the necessary resources to maintain our quality of life and our position in the world as a major power. We must now shift to a lower cost prevention and wellness model of care for chronic illnesses and this is exactly what leaders in healthcare innovation are pursuing. By improving health outcomes through this lower cost approach, we could allocate some of these saved resources to other societal problems such as crime, education, poverty and job creation (4).

Our emphasis on pharmaceutical and medical service prescription is unsustainable.

Lessons learned from Medicare’s pioneer ACO pilot programs tell us that we must reduce medical services by preventing “rising risk” patients from becoming “high risk” patients in order for healthcare to become financially viable in the long term (19). This is why the Institute of Medicine, the CDC (6), the Institute for Healthcare Improvement (33), the American Academy of family Physicians (34), and the Centers for Medicare and Medicaid (30) are calling for a shift in care away from reactive disease management to proactive disease prevention.

These organizations are calling for a reorganization of primary care into highly functioning physician-led prevention teams like the patient-centered medical home where each member of the team takes on different responsibilities and works at the top of their license. The team focuses on prevention and wellness of their assigned population and engages patients in the work of self-management.

Self-management support is a KEY intervention for preventing chronic illness (35) but physicians have received little training in team-based care and in condition or lifestyle self-management prescription (38). In addition, both providers and patients have become accustomed to the medication or procedure-based encounter pointing to the additional challenge of creating a “culture” of prevention and wellness (24, 28).

Self-management support is a KEY intervention for preventing chronic illness

Pre-existing models of successful self-management support programs include cardiac rehabilitation (32% improvement in cardiac mortality) (17), pulmonary rehabilitation (37% reduction in acute hospitalizations for COPD) (16), and the diabetes prevention program (70% reduction in onset of diabetes for older pre-diabetic patients) (14).

The Institute of Medicine has recently called for medical education reform to meet the new demand for prevention and wellness delivery within primary care (10) but this could take many years to implement once medical schools finally embrace these recommendations.

To further elucidate the healthcare “cultural” problem, patients report that they would rather take medications or undergo surgery then make changes in their health behaviors to reduce chronic disease risk factors (24). In order to change this paradigm, the American Hospital Association has called for the enactment of a “culture of wellness” throughout our systems of care (29).

They recognize that the cultural disconnect between the OLD way of reactive care delivery and the NEW way of preventive care delivery. Changing culture takes time and this will be a significant challenge for 21^st century healthcare. The providers who succeed in making this cultural shift sooner then later will be the winners within the NEW value-based payment system that is emerging (19).

Patients report that they would rather take medications or undergo surgery then make changes in their health behavior

Leaders from the Robert Wood Johnson Foundation (11), from Kaiser-Permanente (31), from Cleveland Clinic (32) and many other integrated care systems (18) are working to prevent disease at every level within the chronic disease lifecycle. They are calling for prevention and wellness integration as a primary focus for better outcomes delivery at a reduced cost. This is consistent with Medicare’s triple aim vision for the future of healthcare (18).

With the shift to electronic medical records and the push to get patients “into the system”, more providers will be able to use BIG DATA to identify the right risks for prevention so that limited resources can be targeted in the right way. This is what the Robert Wood Johnson foundation calls “A Prescription for Health” (12) and this is what will sustain healthcare delivery in the long term.

HealthCoach – tracks biomarker information like steps per day, weight (loss or gain), BMI, continuous blood sugar, sleep, hydration and food choices – as well as a host of other cohorts through fitness tracking technology.

HealthCoach – allows doctors, participants and health coaches to use secure HIPAA messaging or video conferencing to help with better food choices, to encourage consistent steps per day, to insure safe weight loss and to communicate data back to the doctor for reassessment every 90 days.

References:

1. Preventing chronic diseases: a vital investment WHO, 2005
2. Origins and evolution of the Western diet: Health implications for the 21st century, Loren Cordain, Am J Clin Nutr, February 2005
3. Healthypeople.gov
4. Congressional Budget Office, 2009
5. Extent and causes of international variations in drug usage. A report for the Secretary of State for Health. July, 2010, UK
6. The Power of Prevention: The Public health Challenge of the 21st Century, CDC 2009
7. USDA.gov
8. The State of U.S. Health, 1990-2010, JAMA, July 2013
9. Diabetes Fact Sheet, 2011, CDC.gov
10. Interview Gail Wilensky, Institute of Medicine Co-chair, Committee on the Governance and Financing of Graduate Medical education, July 2014
11. Interview with James Marks, Director of Program Portfolios, RWJF, US 1 Magazine, Princeton, N.J.
12. Prescriptionforhealth.org
13. Council of Economic Advisors, Whitehouse.gov
14. Reduction in the Incidence of Type 2 Diabetes with Lifestyle Intervention or Metformin, Diabetes Prevention research Group, NEJM; Vol 346:6, 394-403
15. Institute of Medicine. Preventing Medication Errors: Quality Chasm Series, Washington, DC: National Academy Press; 2007.
16. Olivia Revitt, Louise Sewell et. al., Short outpatient pulmonary rehabilitation program reduces readmission following a hospitalization for an exacerbation of chronic obstructive pulmonary disease, Respirology, Volume 18, Issue 7, pages 1063–1068, October 2013
17. Rod S. Taylor, Allan Brown et al., Exercise-Based Rehabilitation for Patients with Coronary Heart Disease: Systemic Review and Meta-analysis of Randomized Controlled Trials, Am J Med 2004; 116: 682-692
18. http://innovation.cms.gov/
19. Population Health, Healthcare Informatics Webinar, Advisory Board Research, March 2014
20. S. Boyd Eaton, Beverly I. Strassman, Randolph Nesse et al., Evolutionary Health Promotion, Preventive Medicine 34, December 2001, 109-118
21. Evolution in Health and Disease (Oxford Biology): January 10, 2008 by Stephen C. Stearns and Jacob C. Koella
22. Dale Bredesen, Reversal of cognitive decline: A novel therapeutic program, AGING, September 2014, Vol 6 N 9
23. Forrest KY1, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011 Jan;31(1):48-54.
24. Allan S. Detsky M.D., PhD, What patients really want from health care? JAMA, December 14, 2011, Vol 306, No. 22
25. OECD Health Data, 2012
26. May Clinic Proceedings, June 2013
27. ABC News, April 20, 2011
28. CDC Faststats, 2013
29. A Call to Action: Creating a Culture of Health, American Hospital Association, January 2011
30. CMS Comprehensive Primary Care Initiative, June 2012 Webinar
31. Healthcare Will Note Reform Itself, George Halvorson, CEO Kaiser Permanente, 2009
32. The Cleveland Clinic Way: Lessons in Excellence from One of the World’s Leading Health Care Organizations Hardcover – January 7, 2014 by Toby Cosgrove
33. Institute for Healthcare Improvement, triple Aim for Populations, http://www.ihi.org/Topics/TripleAim/Pages/Overview.aspx
34. American Academy of family Physicians, Summary of Recommendations for Clinical Preventive Services, November 2014
35. Mary Thoeson Coleman, Karen S. Newton, Supporting Self-management in Patients with Chronic Illness, American Family Physician, 2005 Oct 15; 72 (8): 1503-1510
36. Cardio metabolic Health Congress, Statement of Need, http://www.cardiometabolichealth.org/2013/accreditation.asp
37. Top 10 Prescription Drugs in the U.S., Institute for Healthcare Informatics, 2010
38. Doctors and Patients, Not Talking About Weight, New York Times, March 16, 2010
39. Stephen B. Lewis M.D., FABPMR

The Gerald J. Joseph – HealthCoach Prevention Program (HCPP) empowers both doctors, patients and participants to improve treatment outcomes by safely engaging patients in health-behavior change supported by diet, organic nutraceuticals, and walking.

HealthCoach communicates with participants on a daily basis, and the patient’s physician reviews the results every 90 days.

Participants have the option to be tracked, measured, and monitored in a comprehensive manner by a HealthCoach. This allows for a more complete and customized review of lifestyle activities and biomarkers such as steps, weight, BMI, hydration, blood pressure, continuous blood sugar and sleep.

HealthCoach communicates with you via smart phone, text messaging, and email and is available to you 24/7. This ensures you’re never far away from a motivating message, an answer to a question, a friend to communicate with, or a great meal suggestion.

The HealthCoach Prevention Program is highly individualized and designed to improve both chronic health conditions and cognitive loss.

HealthCoach supports, mentors and tracks participants as a wellness authority, helping my people feel their best through food and lifestyle changes, tailoring individualized and corporate wellness programs to improve health outcomes