Anti-PD1 Immunotherapy May Work Better in Older Melanoma Patients

MedicalResearch.com Interview with:

Ashani Weeraratna, Ph.D. The Ira Brind professor and  Co-program leader of the Immunology, Microenvironment and Metastasis Program  The Wistar Institute Member of Wistar’s Melanoma Research Center Philadelphia 

Dr. Weeraratna

Ashani Weeraratna, Ph.D.
The Ira Brind professor and
Co-program leader of the Immunology, Microenvironment and Metastasis Program
The Wistar Institute
Member of Wistar’s Melanoma Research Center
Philadelphia 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response:  This study shows for the first time that older patients, especially those who have had prior MAPKi therapy fare better than younger patients when treated with anti-PD1. We found that tumors in younger patients and younger mice have higher levels of Tregulatory cells, the cells that regulate other immune cells. This is not true systemically, only within the tumor microenvironment.

We were surprised because we expected that, as with targeted therapy, older patients would have a poorer response to immunotherapy, given what we perceive as a poorer immune system in older patients.  Continue reading

As We Age, Our Circadian Clock Becomes Less Sensitive To Light, Leading To Sleep Problems

MedicalResearch.com Interview with:
“Woman sleeping” by Timothy Krause is licensed under CC BY 2.0Dr Gurprit S. Lall BSc, MSc, PhD, PGCHE, FHEA

Medway School of Pharmacy
Interim Deputy Head of School
Senior Lecturer in Pharmacology
Director of Graduate Studies (Research),
University of Kent at Medway
Chatham Maritime, Chatham, Kent

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Medical advancement in prevention and diagnosis of disease has increased life expectancy significantly, thus generating an ageing population far greater than previously seen.  Because of this, it is essential that we begin to understand the ageing process, together with the health implications associated with senescence.  Recent research has found that changes in the circadian clock, located in the brain, play a contributing role in the decline of many physiological and behavioural traits observed through the ageing process.  One example of this, which is commonly seen in the elderly is a decline in sleep-wake cycle regulation; typically presenting as disrupted sleeping patterns.

The circadian clock, in mammals, possesses the ability to integrate our social lifestyle choices with the environmental day-night cycle to generate a 24-hour rhythm to which our physiological functions are synchronised.  It is this synchronisation that plays a vital role in regulating many of our behavioural outputs, such as sleeping-wake patterns.  This clock takes its strongest timing cue from the natural day night cycle governed by the duration of daily sunlight.

Our study investigated the changes in the interpretation of this light signal by the circadian clock as we age and its impact on function.  We found that the clock became less responsive to light stimuli at both the level of clock cells and at driving behavioural activity.  We were able to narrow this down to changes in the proteins within cells that relay light information to the molecular time setting machinery.  In detail, light signals are relayed to the clock through an excitatory neurotransmitter called glutamate and this signal is predominantly relayed through NMDA receptors located on the surface of clock cells.  It is the configuration of the NMDA receptor that alters as we age and this leads to the clock becoming less responsive to light.

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Alcohol Accelerates Aging of Brain’s Frontal Cortex

MedicalResearch.com Interview with:
alcohol-cdc-image
Edith V. Sullivan, Ph.D.
Professor
Department of Psychiatry & Behavioral Sciences
Stanford University School of Medicine
Stanford, CA 94305-5723 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alcohol misuse is a major public health problem worldwide with profound health consequences on the body, brain, and function. Our research group has conducted naturalistic yet controlled studies of alcohol dependence for several decades to further our understanding of when and how alcohol misuse affects specific parts of the brain.  In addition, we wanted to know how alcohol misuse interacts with the typical changes in the brain as we grow older.  The studies are controlled in that we recruit healthy, non-alcohol dependence men and women from the community to undergo the same screening and neuroimaging procedures as our alcoholic recruits.  The studies are quantitative because we use neuroimaging methods (Magnetic Resonance Imaging) that enable us to measure specific regions of brain structural volumes.  Consistent collection of such data over the years positioned us to ask whether age and alcohol dependence interact to produce regional brain volume loss beyond the loss that occurs in normal aging.

A number of cross-sectional studies pointed to the likelihood that the effects of alcohol dependence on brain structure would be exacerbated by normal aging, which we do know from longitudinal neuroimaging studies results in shrinkage of cortical gray matter volume and thinning of the cortex. What was particularly striking about our longitudinal study of men and women with alcohol dependence was the acceleration of the aging of brain structure that was especially prominent in the frontal cortex.  Critically, even those who initiated dependent drinking at an older age showed accelerated loss.

Because our study sample was large enough, we could also test whether our findings were attributable to conditions that commonly co-occur with alcohol dependence, namely, illicit drug use and hepatitis C.  Although both drug use and hepatitis C infection may have exacerbated brain volume loss, these factors did not fully account for the alcoholism-aging interaction we identified.

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Gene Changes During Aging Predispose To Cancer Formation

MedicalResearch.com Interview with:

Hariharan Easwaran, PhD Assistant Professor of Oncology The Sidney Kimmel Comprehensive Cancer Center The Johns Hopkins University School of Medicine Bunting/Blaustein Cancer Research Building 1 Baltimore, MD 21287

Dr. Easwaran

Hariharan Easwaran, PhD
Assistant Professor of Oncology
The Sidney Kimmel Comprehensive Cancer Center
The Johns Hopkins University School of Medicine
Bunting/Blaustein Cancer Research Building 1
Baltimore, MD 21287

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The interpretation of the information encoded in our DNA by the various cells in our body is mediated by a plethora of modifications of DNA and proteins that complex with DNA. DNA methylation is one such important modification, which is normally established in a very orchestrated fashion during development. All normal cells have a defined pattern of DNA methylation, which may vary by tissue type, but is consistent within tissues. This normal pattern is disrupted in all known cancers, and is considered a hallmark of cancers.

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How Old is Old?

MedicalResearch.com Interview with:
“Im Spiegel / In the mirror” by njs-photographie is licensed under CC BY-NC-ND 3.0William Chopik PhD
Department of Psychology
Michigan State University
East Lansing, MI 

MedicalResearch.com: What is the background for this study?

Response: The motivation for the study was that we saw a lot of differences in the way people defined “old age”. We also noticed that there is a stigma that goes along with being old. So we had a natural curiosity to see how these perceptions my change as people age.

As people aged, the tended to report feeling younger and consider an older adult as “always in the future”–never quite where they are now.

We found that our results confirmed a lot of existing theories about how our attitudes toward aging change as we age ourselves.

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Patients With Multiple Chronic Diseases Incur High Out-of-Pocket Expenses

MedicalResearch.com Interview with:

Dr Grace Sum Chi-En National University of Singapore

Dr Grace Sum    Chi-En

Dr Grace Sum Chi-En
National University of Singapore

MedicalResearch.com: What is the background for this study?

Response: Chronic diseases are conditions that are not infectious and are usually long-term, such as diabetes, hypertension, cancer, chronic lung disease, asthma, arthritis, stroke, obesity, and depression. They are also known as non-communicable diseases (NCDs). Multimorbidity, is a term we use in our field, to mean the presence of two or more NCDs. Multimorbidity is a costly and complex challenge for health systems globally. With the ageing population, more people in the world will suffer from multiple chronic diseases.

Patients with multimorbidity tend to need many medicines, and this incurs high levels of out-of-pocket expenditures, simply known as cost not covered by insurance. Even the United Nations and World Health organisation are recognising NCDs as being an important issue.

Governments will meet in New York for the United Nations 3rd high-level meeting on chronic diseases in 2018. Global leaders need to work towards reducing the burden of having multiple chronic conditions and providing financial protection to those suffering multimorbidity.

Our research aimed to conduct a high-quality systematic review on multimorbidity and out-of-pocket expenditure on medicines.  Continue reading

Activation of Telomerase Will Not Cure Aging

MedicalResearch.com Interview with:

Douglas P. Kiel, MD, MPH Professor of Medicine Harvard Medical School Director Musculoskeletal Research Center Institute for Aging Research, Hebrew SeniorLife Associate Member Broad Institute of Harvard and MIT

Dr. Kiel

Douglas P. Kiel, MD, MPH
Professor of Medicine
Harvard Medical School
Director Musculoskeletal Research Center
Institute for Aging Research, Hebrew SeniorLife
Associate Member Broad Institute of Harvard and MIT 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Why we age? and how we age?, are perennial questions that are of interest to all. The research described in this publication brings together two major and different concepts of aging – epigenetic aging, which is manifested by modifications on DNA and telomere-related aging, which is manifested by shortening of chromosome ends (telomeres).  In our search for genes that could potentially affect epigenetic aging, we detected  a variant of the TERT gene (whose encoded protein, telomerase maintains telomere length) to be associated with accelerated epigenetic aging. TERT is a subunit of the enzyme telomerase which is a widely known enzyme for the following reasons:

1)    Telomerase has been touted as an anti-aging enzyme. It has been called a modern fountain of youth. However, some scientists have pointed out that it is unlikely to become a source of anti-aging therapies (see the review article by de Magalhães JP1, Toussaint in Rejuvenation Research (2004) .https://www.ncbi.nlm.nih.gov/pubmed/15312299)   Our new results gained by the epigenetic clock also indicate that telomerase will not halt organismal aging.

2)    The book “The Telomere Effect” by Nobel prize winner Elizabeth Blackburn and Elissa Epel was on the New York Times best seller list and received substantial news coverage:https://www.cbsnews.com/news/telomere-effect-book-living-younger-healthier-longer/

Our data provides a much needed  understanding of the molecular drivers of the epigenetic clock and reveal a unexpected and paradoxical connection between two seemingly distinct aging clocks: the telomere clock and the epigenetic clock.

Our main finding was that variants in the human telomerase reverse transcriptase gene (TERT) were associated with increased “intrinsic epigenetic aging.” 

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Seniors Entering Old Age Will Increasingly Have Multiple Complicated Health Conditions

MedicalResearch.com Interview with:

Prof. Carol Jagger AXA Professor of Epidemiology of Ageing and Deputy Director of the Newcastle University Institute for Ageing (NUIA) Institute of Health & Society Campus for Ageing and Vitality Newcastle

Prof. Jagger

Prof. Carol Jagger
AXA Professor of Epidemiology of Ageing and
Deputy Director of the Newcastle University Institute for Ageing (NUIA)
Institute of Health & Society
Campus for Ageing and Vitality
Newcastle 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: As part of a larger study (MODEM – modelling outcome and cost impacts of interventions for dementia) we have developed a microsimulation model called PACSim which forecasts the number of older people aged 65 years and over along with their health and lifestyle factors as they age over the next 20 years. Crucially these are the first projections that include the health and lifestyle profiles of younger people as they age into to older population, rather than just assuming they have the same health profiles as existing young-old.

Other studies have already reported that the proportion of older people with multimorbidity (two or more concurrent diseases) has increased. Our study shows that not only will this continue but that the largest increase over the next 20 years will be for complex multimorbidity (four or more diseases). Much of the gain in life expectancy over the next 20 year for a 65 year old will be years spent with complex multimorbidity. And more importantly the future cohorts of young-old entering the older population will have successively more multimorbidity. Continue reading

Early Studies Suggest Blood Pressure Medication Hydralazine May Slow Aging and Neurodegeneration

CrawlingCelegans Wikipedia

Crawling C. elegans
Wikipedia image

MedicalResearch.com Interview with:
Hamid Mirzaei, Ph.D.
Assistant Professor of Biochemistry
University of Texas Southwestern
Department of Biochemistry
Dallas, TX 75390

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Aging is a complex process at the cellular level with distinct organismal phenotypes. Despite millennia-old obsession with aging and relentless pursuits for ways to stop and reverse it, such elixir has not been found due to the complexity of the involved mechanisms and our limited understanding of the processes that lead to aging. Although progress has been made in recent years in slowing down the aging process in model organisms and human cells.

In this study, we report that and FDA approved antihypertensive drug, hydralazine, decelerates aging in C. elegans by mechanisms that seem to resemble dietary restriction. We show that hydralazine increases the median lifespan of the C. elegans by 25% which is comparable to or better than other known antiaging compounds.

We demonstrate that not only hydralazine-treated worms live longer, they appear to be healthier in general. Because aging is directly linked to neurodegenerative diseases, we tested our drug on both in vitro and in vivo models of neurodegenerative diseases using chemical and biological stressors (rotenone and tau fibrils) and show that hydralazine has neuroprotective properties as well.

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Doing Something Is Better Than Nothing: Even Light Physical Activity Improves Health

MedicalResearch.com Interview with:

Michael J. LaMonte, PhD, MPH Research Associate Professor Department of Epidemiology and Environmental Health Co-Director, MPH Program (epidemiology) School of Public Health and Health Professions Women’s Health Initiative Clinic University at Buffalo – SUNY 

Dr. LaMonte

Michael J. LaMonte, PhD, MPH
Research Associate Professor
Department of Epidemiology and Environmental Health
Co-Director, MPH Program (epidemiology)
School of Public Health and Health Professions
Women’s Health Initiative Clinic
University at Buffalo – SUNY 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Current national public health guidelines recommend 150 minutes of moderate to vigorous physical activity a week for adults. The guidelines recommend persons 65 and older follow the adult guidelines to the degree their abilities and conditions allow. Some people, because of age or illness or deconditioning, are not able to do more strenuous activity. Current guidelines do not specifically encourage light activity because the evidence base to support such a recommendation has been lacking.

Results from the Objective Physical Activity and Cardiovascular Health (OPACH) Study, an ancillary study to the U.S. Women’s Health Initiative, recently published in the Journal of the American Geriatrics Society showed women ages 65-99 who engaged in regular light intensity physical activities had a reduction in the risk of mortality. The 6,000 women in the OPACH study wore an activity-measuring device called an accelerometer on their hip for seven days while going about their daily activities and were then followed for up to four and a half years.  Results showed that just 30 additional minutes of light physical activity per day lowered mortality risk by 12 percent while 30 additional minutes of moderate activity, such as brisk walking or bicycling at a leisurely pace, exhibited a 39 percent lower risk. 

The finding for lower mortality risk associated with light intensity activity truly is remarkable. We anticipated seeing mortality benefit associated with regular moderate-to-vigorous intensity activity, as supported by current public health guidelines. But, observing significantly lower mortality among women who were active at levels only slightly higher than what defines being sedentary was such a novel finding with important relevance to population health.

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Aging Population, Socio-Economic Disparities Linked To Increase in Heart Failure Incidence

MedicalResearch.com Interview with:

Prof Kazem Rahimi FRCP The George Institute for Global Health Oxford Martin School University of Oxford, Oxford

Prof. Rahimi

Prof Kazem Rahimi FRCP
The George Institute for Global Health
Oxford Martin School
University of Oxford, Oxford

MedicalResearch.com: What is the background for this study?

Response: We decided to investigate this topic because disease incidence data is very important for public health bodies; for example, for the allocation of healthcare resources or for the design and assessment of disease prevention measures.

When we reviewed the literature, we found that estimates of heart failure incidence, temporal trends, and association by patient features were scarce. Studies often referred to restricted populations (such as relatively small cohorts that may or may not be representative of the general population), or limited data sources (for example, only including patients hospitalized for their heart failure and not considering those diagnosed by clinicians outside of hospitals). Few studies reported comparable, age-standardized rates, with the result that the rates reported varied considerably across the literature.

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Having a Dog May Help You Live Longer

MedicalResearch.com Interview with:

Tove Fall PhD Senior author of the study Associate Professor in Epidemiology Department of Medical Sciences and the Science for Life Laboratory Uppsala University.

Dr. Fall

Tove Fall PhD
Senior author of the study
Associate Professor in Epidemiology
Department of Medical Sciences and the Science for Life Laboratory
Uppsala University

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Loneliness and sedentary lifestyle are two major risk factors for cardiovascular disease and mortality, but are notoriously difficult to prevent in the general population.

Previous studies have shown that dogs may serve as a strong motivator for daily exercise, provide substantial social support and have a positive effect on the owner’s gut microbiome. The effects of pet dogs on health outcomes in the general population are largely unknown.

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With Aging, Males and Females Express Genes Differently

MedicalResearch.com Interview with:
Dr Mandy Peffers BSc MPhil PhD BVetMed FRCVS
Wellcome Trust Clinical Intermediate Fellow
Institute of Ageing & Chronic Disease
Faculty of Health & Life Sciences
University of Liverpool Liverpool UK

MedicalResearch.com: What is the background for this study?

Response: The project was an extension of Louise Pease’s MSc research project in bioinformatics which aimed to re-analyse existing RNA-seq data to determine age related changes in gene expression in musculoskeletal tissues that may lead to the development of degenerative diseases.  From existing literature we identified that degenerative diseases such as osteoarthritis and tendinitis were more prevalent in females and became more frequent following menopause.  We looked at the biology of the cohort we were trying to assess and discovered a gender imbalance, we hypothesised that this was why few results had been obtained from the original analysis. So we developed a research proposal that detailed extending the existing data to publicly available data and merging the experiments; to increase the number of replicates available and balance the experimental design.  We conducted multiple analyses and discovered that splitting samples by age and gender obtained the most significant results, and that whilst in a lot of cases the same genes were being differentially expressed, they were changing in opposite directions.  Louise remembered her statistics lecturer Gerard Cowburn (Ged) taught her about the assumptions of statistical tests, in particular covariance analysis (which has previously been used to show that age and gender do not affect gene expression) assumed that under the conditions being tested data points were not opposites.  Realising that this assumption had been violated by the data she began to think about what other assumptions we were working with and how to test their validity.

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Focusing on Physical Activity Can Help Avoid Unnecessary Later Life Social Care Expenses

MedicalResearch.com Interview with:
Dr. Scarlett McNally

Consultant Orthopaedic Surgeo
Eastbourne D.G.H.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are vast differences between older people in their abilities and their number of medical conditions. Many people confuse ageing with loss of fitness. Ageing has specific effects (reduction in hearing and skin elasticity for example) but the loss of fitness is not inevitable. Genetics contributes only 20% to diseases. There is abundant evidence that adults who take up physical activity improve their fitness up to the level of someone a decade younger, with improvements in ‘up and go’ times. Physical activity can reduce the severity of most conditions, such as heart disease or the risk of onset or recurrence of many cancers. Inactivity is one of the top four risk factors for most long-term conditions. There is a dose-effect curve. Dementia, disability and frailty can be prevented, reduced or delayed.

The need for social care is based on an individual’s abilities; for example, being unable to get to the toilet in time may increase the need for care from twice daily care givers to needing residential care or live-in care, which increases costs five-fold.

Hospitals contribute to people reducing their mobility, with the ‘deconditioning syndrome’ of bed rest, with 60% of in-patients reducing their mobility.

The total cost of social care in the UK is up to £100 billion, so even modest changes would reduce the cost of social care by several billion pounds a year.

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Gut Microbiome of Health Very Old Similar To Younger Adults

MedicalResearch.com Interview with:
Greg Gloor, PhD
Principal investigator
Professor at Western’s Schulich School of Medicine & Dentistry and
Scientist at Lawson Health Research Institute.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We sampled the bacteria in the gut (stool) in over 1000 members of a super healthy population in China across the age ranges of 3 to over 100. Exclusion criteria included a history of genetic or chronic disease (intergenerational in the case of people younger than 30), no smoking, drinking or drug use (including no prescription drugs).

Our goal was to identify what, if any changes in the makeup of the gut microbiota occurred in this population so that we could define “what is associated with health”.

We found three things.

  • First, that the expected differences between the very young and everyone else were found in this population. This indicates that we could observe the standards signatures of a maturing gut microbiota.
  • Second, that the gut microbiota of very healthy very elderly group (over 95 yo) was very similar to that of any very healthy person over the age of 30.
  • Third, we found that the gut microbiota of 20yo people (in three distinct groups) was different from all other age groups. The reason for the differences observed in the 20 yo groups from all the others is unknown, but is not methodological in origin.

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