Dr. Ravindrarajah[/caption]
Dr. Rathi Ravindrarajah PhD
Division of Health and Social Care Research
Faculty of Life Sciences & Medicine
Guy’s Campus
King’s College London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Clinical trials show that it is beneficial to lower systolic blood pressure (SBP) in adults aged 80 and over, but non-randomized epidemiological studies suggest that lower systolic blood pressure may be associated with a higher risk of mortality.
Our main findings were that there was a terminal decline in systolic blood pressure in the final 2 years of life suggesting that the higher mortality in those with a low SBP shown in non-randomized epidemiological studies might be due to reverse causation.
Dr. Liu[/caption]
Leyuan Liu, Ph.D., Assistant Professor
Center for Translational Cancer Research
Institute of Biosciences and Technology
Texas A&M University
Houston, Texas 77030
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Our research team has been working on the question why people develop cancers and how we can prevent or cure them. In contrast to public views, we concluded from our studies that cancers, similar to our age-related diseases, originate from inefficiencies of our body to clean up cellular wastes accumulated during our lifespan. The most important pathway to clean up those wastes is called autophagy, or cellular self-eating behavior. We study how autophagy is regulated, how autophagy causes cancers, and whether we can control autophagy to prevent or cure cancers.
Previously we found autophagy is regulated by a protein called MAP1S and mice without MAP1S are more likely to develop liver cancer. We have been seeking ways to improve MAP1S-mediated autophagy to prevent liver cancer. Our current study show that spermidine, a natural component existing in many foods, can increase the stability of MAP1S proteins and activate MAP1S-mediated autophagy. Concurrent with the benefits of expand mouse lifespans ours also reported, spermidine can suppress the development of liver fibrosis and liver cancer specifically through MAP1S if we add spermidine into the daily drinking water of mice.
Dr. Modig[/caption]
Dr. Karin Modig, PhD
Institute of Environmental Medicine,Epidemiology
Karolinska Institute
MedicalResearch.com: What is the background for this study?
Response: The background to the study was that even though it is established that parents live longer than non-parents the underlying mechanisms are not clear. And it was not known how the association changed with the age of the parents. We hypothesize that if social support is one mechanism – the association between having children and the death risk of parents-non-parents would increase with age of the parents, when health starts to deteriorate and the need of support increases.
Ana O'Loghlen[/caption]
Ana O'Loghlen
Group Leader Epigenetics & Cellular Senescence
Blizard Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The activation of senescence is an important cellular response to a stress signal. The senescent cell stops proliferating and this avoid that damaged cells propagate in our body, creating tissue damage.
Our study has found a particular protein, integrin beta 3 subunit, regulating this cellular phenotype, senescence. We have further provided details of the mechanism of how this integrin does this. We have found that the activation of the TGF beta pathway is important for integrin beta 3 to induce senescence and that this integrin is regulated by epigenetically by the polycomb protein CBX7. Interestingly, although we have not provided functional studies, we find that integrin beta 3 is highly expressed during aging in human and mouse.
Dr. Emma van Bussel[/caption]
Emma van Bussel MD, MSc
Academic Medical Center | University of Amsterdam
Amsterdam | The Netherlands
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Dementia forms a high social and economic burden on society. Since there is a growing number of older people, the occurrence of dementia is expected to increase over the years to come. For future planning of care, it is important to have reliable predictions on new dementia cases for the population at large. Studies in Western countries suggested that the incidence per 1000 person years is declining.
We studied the incidence trend of dementia in the Netherlands in primary care registry data, in a population of over 800,000 older people (60 years and over) for the years 1992 to 2014. Our results indicate a small increase of 2.1% (95% CI 0.5% to 3.8%) per year in dementia incidence over the past decades. The trend did not change in the years after 2003, when a national program was developed to support dementia care and research, compared to the years prior to 2003.
Dr. Behera[/caption]
Reeti Behera, Ph.D.
Postdoctoral fellow in the Weeraratna lab
The Wistar Institute
Philadelphia PA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Malignant melanoma is an aggressive disease and is the cause of the majority of skin cancer deaths. In particular, older individuals have a much poorer prognosis for melanoma and are more resistant to targeted therapy than compared to young individuals. A recently published study from our lab has shown that age-related changes in secreted factors in the microenvironment can drive melanoma progression and therapy resistance.
Klotho is a protein whose expression levels decreases with aging. In this study, we have shown that a decrease in klotho levels in the aged microenvironment drives melanoma aggression and therapy resistance by promoting the oncogenic signaling pathway Wnt5A. We also have shown that reconstituting klotho levels in the aged microenvironment by using rosiglitazone, an FDA-approved drug used to treat diabetes, can reduce tumor burden in aged mice. We also show that Klotho expression is decreased in therapy-resistant melanoma tumors. Reconstituting klotho levels in therapy-resistant melanoma cells by treating with rosiglitazone can inhibit Wnt5A levels and MAPK pathway. We also show that rosiglitazone can significantly decrease therapy-resistant tumor burden in the aged mice, but not in the young.
Dr. John Price[/caption]
John C. Price, Ph.D
Asst. Professor Chemistry and Biochemistry
Brigham Young University
Provo, Utah
MedicalResearch.com: What is the background for this study?
Response: Since 1930 it has been known that the rate of biological aging could be modified by the diet. In mice for example if you let them eat as much as they want they will live almost 3 years. Providing essentially the same diet but controlling the number of total calories, there is an almost linear increase in lifespan as you restrict calories. The studies in mice and rats have been repeated hundreds of times since that time. There have been a lot of somewhat conflictive observations, like increased formation of new mitochondria, and increased autophagy which targets organelles for degradation, during stable reduced calorie intake. This expectation, that a restricted diet with fewer calories available to the animal could support increased protein synthesis and degradation and result in increased lifespan, is what got us interested in studying Calorie Restriction. So we measured the relative synthesis rates for several hundred proteins in 18 month old calorie restricted mice which were experiencing the benefits of improved health and lifespan. We found overwhelmingly that the calorie restricted mice had reduced synthesis rates down to as low as 25% of the age matched control group. This observation has now been independently confirmed by multiple groups.
Dr. Paola Sebastiani[/caption]
Paola Sebastiani PhD
Department of Biostatistics
Boston University School of Public Health
Boston, MA 02118
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Human life expectancy has increased steadily in the last century and has led to a growth of the elderly population and a need for prevention strategies and interventions that promote healthy aging.
A challenge in assessing the effect of such interventions is ‘what to measure’ because people can age very differently from one another. Our study used 19 blood biomarkers that include for example cholesterol level and hemoglobin A1C to discover 26 biological signatures of aging in approximately 4,700 participants of the Long Life Family Study. These signatures are essentially patterns of values of the 19 biomarkers and we showed that one of these signatures is associated with better physical and cognitive functions, and reduced risk for disease and mortality compared to the most common signature in the study. Additional signatures predict varying risk for diabetes, cardiovascular and other aging-related diseases. We replicated these results in an independent data set. The associations of these biomarker signatures with physical and cognitive functions, and risk for morbidity and mortality support the conclusion that they capture different form of biological aging.
Dr. Belmonte[/caption]
Juan Carlos Izpisua Belmonte PhD
Professor, Roger Guillemin Chair
Salk Institute of Biological Science's Gene Expression Laboratory
MedicalResearch.com: What is the background for this study?
Response: Previous studies from different laboratories including ours demonstrated that cellular reprogramming to pluripotency has the capacity to rejuvenate old cells in culture (in a dish) to a younger state. In 2011, we published a study in Nature demonstrating that cellular reprogramming could rejuvenate cells from patients suffering from Hutchinson–Gilford progeria syndrome (HGPS), a premature aging syndrome. The current study started after this publication back in 2012 and the two major questions that we had were:
-Could partial, but not complete, cellular reprogramming rejuvenate cells?
-Could partial reprogramming rejuvenated cells in a living organism improving its health and lifespan?
Dr. Jerry Shay[/caption]
Jerry W. Shay PhD
Professor
Department of Cell Biology,
UT Southwestern Medical Center
MedicalResearch.com: What did you find?
Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population.
Anneke I. den Hollander, PhD
Department of Ophthalmology and Department of Human Genetics
Donders Institute for Brain, Cognition, and Behaviour
Radboud University Medical Center
Nijmegen, the Netherland
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Age-related macular degeneration is caused by a combination of genetic and environmental factors. Rare genetic variants in the complement system have been described in AMD, but their effect remains largely unexplored. In this study we aimed to determine the effect of rare genetic variants in the complement system on complement levels and activity in serum.
MedicalResearch.com: What are the main findings?
Response: Carriers of CFI variants showed decreased FI levels, carriers of C9 Pro167Ser had increased C9 levels, while C3 and FH levels were not altered. Carriers of CFH and CFI variants had a reduced ability to degrade C3b, which for CFI was linked to reduced serum FI levels.
Dr. Christina Fitzmaurice[/caption]
Christina Fitzmaurice, MD, MPH
Assistant Professor
Department of Medicine, Division of Hematology
Institute for Health Metrics and Evaluation
University of Washington
Seattle, WA
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Cancer is the second leading cause of death worldwide behind cardiovascular diseases. We found that cancer cases increased by 33% from 13.1 million cases in 2005 to 17.5 million in 2015. The largest driver behind this increase was an aging population, followed by a growing population worldwide. The smallest factor contributing to this increase was a rise in cancer incidence rates. Because of increasing life expectancy and better control of communicable diseases cancer will remain a major burden in the foreseeable future. Adjusting and building health systems that can appropriately deal with this challenge is only possible with good data on the burden of cancer. In our study we estimate the number of cancer cases, and cancer deaths over time for 32 cancers in 195 countries and territories from 1990 to 2015. We also estimate how many years of life were lost due to cancer as well as disability adjusted life years and a summary measure that combines these two into disability adjusted life years.
Dr. John P. Haran[/caption]
John P. Haran, MD
Assistant Professor
Department of Emergency Medicine
University of Massachusetts Medical School
UMass Memorial Medical Group
Worcester, MA
MedicalResearch.com: What is the background for this study?
Response: In 2014, the Infectious Disease Society of America (IDSA) updated their guidelines for the management of skin and soft tissue infection in response to high MRSA infection rates as well as high treatment failure rates for skin and soft tissue infections. Greater than 1 in 5 patients treated for a skin abscess will fail initial treatment.
Historically antibiotics have been shown to be unnecessary in the treatment of uncomplicated purulent infections. This notion has been recently challenges when authors published a randomized control trial using trimethoprim-sulfamethoxazone in the NEJM that demonstrated a minimal increase in cure rates for outpatient treatment of uncomplicated skin purulent skin infections. In this study they did not follow IDSA-guidelines nor model or stratify their analysis. It is possible their findings may be due to at-risk patient groups that did not receive antibiotics. Many widely used clinical decision rules incorporate age into their decision algorithms, however the IDSA did not do this with their recent guidelines.
Dr. Simon Ribero[/caption]
Simone Ribero, M.D., Ph.D.
University of Turin
Department of Medical Sciences
Turin. Italy &
King’s College London
Department of Twin Research and Genetic Epidemiology
St Thomas’ campus
London
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: For many years dermatologists have identified that the skin of acne sufferers appears to age more slowly than in those who have not experienced any acne in their lifetime.
We have demonstrated in our paper that there is an association between acne and longer telomere length that means that acne patients , with the same anagraphic age , have a younger chronological age.
Dr. Gwen Bergen[/caption]
Gwen Bergen, PhD
Division of Unintentional Injury
National Center for Injury Prevention and Control
CDC
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Older adult falls are the leading cause of injury death and disability for adults aged 65 years and older (older adults). In this study, we analyzed data from the Centers for Disease Control and Prevention’s (CDC) Behavioral Risk Factor Surveillance System (BRFSS) survey. Our study found that, in 2014, older Americans reported 29 million falls. Almost a quarter of these or 7 million falls required medical treatment or restricted activity for at least one day. Women reported a higher percentage of falls (30%) compared with men (27%). Whites and American Indian/Alaskan Natives (AI/AN) were more likely to fall compared with Blacks and Asian/Pacific Islanders; and AI/AN were more likely to report a fall injury compared with all other racial/ethnic groups. The percentage of older adults who reported a fall varied by state, ranging from 21% in Hawaii to 34% in Arkansas.
MedicalResearch.com Interview with:
Dr. Bastiaan Heijmans
Leiden University Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Epigenetic change is a hallmark of ageing but its link to ageing mechanisms in humans remains poorly understood. While DNA methylation at many CpG sites closely tracks chronological age, DNA methylation changes relevant to biological age are expected to gradually dissociate from chronological age, mirroring the increased heterogeneity in health status at older ages.
In a large-scale analysis of the methylome of over 3000 individuals, we discovered and validated 6000 sites in the genome that became more variable in their DNA methylation level with age. These sites frequently co-localized with repressed regions that are characterized by polycomb repression. While sites accumulating variability with age were commonly associated with the expression of (neuro)developmental genes in cis, they were linked to transcriptional activity of genes in trans that have a key role in well-established ageing pathways such as intracellular metabolism, apoptosis, and DNA damage response.
Dr. Janice Atkins[/caption]
Dr Janice Atkins
Research Fellow
Epidemiology and Public Health
University of Exeter Medical School
RD&E Hospital Wonford
Barrack Road, Exeter
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We have previously shown that having longer-lived parents increases your likelihood of living longer, and family history of heart attacks is already used by physicians to identify patients at increased risk of disease. However, it has been unclear how the health advantages of having longer lived parents is transferred to their middle-aged offspring.
Our study of nearly 200,000 UK volunteers aged 55-73 at baseline, and followed for 8 years using health records data, found that having longer-lived parents reduced the risk of morbidity and mortality in the participants. We found that for each parent that lived beyond 70 years of age the participants had 20% less chance of dying from heart disease. To illustrate this, in a group of 1,000 people whose father’s died at 70 and followed for 10 years, on average 50 would die from heart disease. When compared to a group whose father’s died at 80, on average only 40 would die from heart disease over the same 10-year period. Similar trends were seen in the mother’s.
The relationship between parental age at death and survival and health in their offspring is complex, with many factors playing a role. Shared environment and lifestyle choices play a large role, including smoking habits, high alcohol consumption, low physical activity and obesity; but even accounting for these factors parents lifespan was still predictive in their offspring. The biggest genetics effects on lifespan in our studies affected the participant’s blood pressure, their cholesterol levels, their Body Mass Index, and their likelihood to be addicted to tobacco. These are all factors that affect risk of heart disease, so is consistent with the lower rates of heart disease in the offspring.
Dr. Lisa Ronan[/caption]
Dr. Lisa Ronan, PhD
Department of Psychiatry
University of Cambridge Neuroscience
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: A growing body of literature relates common markers of aging to those observed in obesity and supports the hypothesis that obesity may accelerate or advance the onset of brain aging. To investigate this relationship at a population level we analysed the white matter volume of the brain in 473 adult subjects ages 20 - 87 years and contrasted these volumes between subjects who were lean (BMI between 18.5 - 25) and those who were overweight / obese (BMI > 25).
Our results suggest that the latter group had significantly smaller white matter volumes when compared to their lean age-matched counterparts. We found that this difference in volume equated to a brain-age increase of 10 years in the overweight / obese group. We found no evidence that obesity impacted on cognitive ability.
Dr. Levine[/caption]
Morgan Elyse Levine, PhD
Postdoctoral Fellow
Department of Human Genetics
University of California, Los Angeles
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: From an evolutionary perspective, aging and reproduction are two processes that are linked. For instance, in order to maximize fitness, an individual has to survive and remain healthy enough to:
1) reproduce and
2) insure offspring survive to reproductive age.
Thus, the rate of aging is tied to a species’ timing of reproductive senescence and necessary length of parental involvement. There is also evidence that among humans, women with longer reproductive stages (later age at menopause, ability to conceive at older ages) are more likely to live to age 100, which we hypothesize is because they age slower.
Using an epigenetic biomarker believed to capture biological aging (previously developed by the Principle Investigator of this study, Steve Horvath), we tested whether age at menopause, surgical menopause, and use of menopausal hormone therapies were associated with a woman’s aging rate.
We found that the blood of women who experienced menopause at earlier ages (especially those who underwent surgical menopause) was “older” than expected, suggesting they were aging faster on a biological level than women who experienced menopause at later ages. We also found that buccal epithelium samples (cells that line the inside of the cheek) were epigenetically younger than expected (signifying slower aging) for post-menopausal women who had taken menopausal hormone therapy, compared to post-menopausal women who had never taken any form of menopausal hormone therapy.
Finally, we had a number of results that suggested that the previously mentioned findings were a result of the process of menopause directly speeding up the aging process—rather than the alternative explanation, which would have been that women who aged faster experience menopause earlier.
Dr. Sofiya Milman[/caption]
Sofiya Milman, MD, MS
Assistant Professor of Medicine
Divisions of Endocrinology and Geriatrics
Albert Einstein College of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Aging is a major risk factor for most chronic diseases, including cancer, cardiovascular disease, diabetes, hypertension, stroke and osteoporosis. However, many very long-lived individuals delay the onset or never develop age-related diseases. This study compared groups of individuals with exceptional longevity (age ≥95 years) of different genetic and ethnic backgrounds to younger referent groups without familial longevity (age 49-93 years). Long-lived individuals from different groups similarly delayed the age of onset of cancer, cardiovascular disease, hypertension, osteoporosis, and stroke. For example, cancer onset was delayed by 30 years and cardiovascular disease by 24 years. The risk of developing any age-related disease was on average 80% lower in individuals with exceptional longevity compared to referents.
Dr. Ava Shamban[/caption]
Dr. Ava Shamban MD
Assistant Clinical Professor of Dermatology
UCLA-Geffen School of Medicine
MedicalResearch.com Editor’s note: Dr. Ava Shamban, a dermatologist frequently featured on CBS’ The Doctors as the skin maven on ABC’s Extreme Makeover discusses the recent announcement of the 20th Global Anniversary of Restylane.
MedicalResearch.com: Would you briefly explain what Restylane® is? What are the main indications for the Restylane® portfolio of products?
Response: Restylane is a non-animal, stabilized hyaluronic acid (NASHA), a unique patented HA stabilization technology which contains pure hyaluronic. The Restylane family of products can be used to design individualized treatments with natural-looking results and long-lasting effects. With 190 scientific publications and 150 clinical studies, and more than 3,000 patients in clinical studies, the Restylane family of products are safe and effective products that have been FDA approved based on extensive clinical data. Restylane® is one of the world’s most studied wrinkle fillers and has been used in more than 65 countries worldwide in over 28 million treatments.
The main indications for the Restylane portfolio products is to improve the overall appearance of the aging face. Whether you’re young or old, whether you have a fine line or wrinkle or a deeper fold there is a product in this portfolio that can improve the appearance of your face and reverse signs of aging.
Dr. Kathleen Fischer[/caption]
Kathleen Fischer, PhD
Department of Biology
UAB | University of Alabama Birmingham
Birmingham, AL
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Fischer: Aging is by far the greatest risk factor for most of the chronic, non-communicable diseases (e.g. cardiovascular disease, cancer, diabetes). By discovering the basic mechanisms responsible for aging we can find ways to extend healthy and productive life and reduce the burdens of chronic disease and disability experienced by individuals and society. Sex differences in longevity can provide novel insights into the basic biology of aging; however this aspect of aging has been largely ignored.
Demographic data show that women outlive men in every society during every historical period and in every geographic area. In spite of this robust survival advantage, women suffer far greater morbidity late in life—a phenomenon described as the morbidity-mortality paradox. It is not clear whether this is a general mammalian pattern or something unique to humans. Research on sex differences in aging and age-related diseases in humans and a range of species will be crucial if we are going to identify the basic mechanisms responsible for the patterns we observe.
Dr. Catherine Diefenbach[/caption]
Dr. Catherine S. M. Diefenbach MD
Assistant Professor of Medicine
NYU Cancer Center
New York, NY 10016
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Diefenbach: It is well known that age is important prognostic factor in non-Hodgkin’s lymphoma (NHL). Multiple studies have illustrated that elderly lymphoma patients have inferior survival outcomes as compared to their younger counterpart. While the tumor biology is often different in these two groups, and may play a role in this discordancy, elderly patients are often frail or have multiple medical comorbidities. These include geriatric syndromes, such as: cognitive impairment, falls, polypharmacy, and potentially inappropriate medication (PIM) use. All of these may contribute to poor outcomes for elderly patients. In addition, elderly patients are often under-treated for their aggressive lymphoma out of concern for toxicity or side effects, even though the data clearly demonstrates that elderly patients can still benefit from curative intent chemotherapy.