Carlos F. Sánchez Ferrer: “Drugs that are able to inhibit the actions of adipokines can have a beneficial effect on arteries and can even reverse vascular aging”

The first session of #Longevity19 will approach longevity from different perspectives. For example, Professor Carlos F. Sánchez Ferrer will explain the new pharmacological targets as far as vascular ageing is concerned. His training and experience endorse his voice as a reference in this sector which is currently celebrating its world congress.

In your opinion, what has been the most important step forward during the course of the last year, in terms of life expectancy and quality of life?  

I’m not sure there’s been any one particular step forward that is more important than all the others. I believe that there is a progressive accumulation of information and that this increase in quantity will eventually lead to qualitative progress.

What mechanisms of human cardiovascular aging can be treated, slowed, or reversed?

Back in the 18th century, an English doctor called Thomas Sydenham stated that “A man is as old as his arteries are”, which also applies to women, of course. This aging can be slowed and even reversed by implementing healthy lifestyles, including the Mediterranean diet and physical exercise.

From a pharmacological point of view, we also know that some of the medicines we use to treat diseases such as high blood pressure and high cholesterol have positive effects and delay cardiovascular ageing. Statins, which reduce LDL (the so-called “bad”) cholesterol levels, have beneficial effects on the arteries not only because of this mechanism, but also because of other effects which we call “pleiotropic” and which are still under study.  We also know that drugs that inhibit the renin-angiotensin system and which are widely used in the treatment of arterial hypertension, also reduce several pathological processes associated with vascular aging.

On the other hand, certain metabolic diseases can sometimes have catastrophic consequences for the cardiovascular system, such as type 2 diabetes mellitus which is characteristic of people of a certain age and is frequently associated with obesity. They are in fact considered to be progesterone-related  diseases, i.e. diseases that favour ageing. Nowadays, in order to treat these so-called cardiometabolic diseases, it is considered crucial that we come up with drugs that not only improve the metabolic aspects, but above all the cardiovascular consequences.

What research is being carried out on this subject in the pharmacological field?

In obesity and diabetes mellitus, the hypertrophied adipose tissue is capable of producing and releasing different substances, which are called adipocytokines or adipokines, and which are now used as disease markers, i.e. their presence is considered diagnostic or prognostic. We believe that these substances, per se, can have harmful effects on the arteries and are therefore mediators that lead to the development of cardiovascular disease. If this hypothesis is confirmed, adipokines would become therapeutic targets, i.e. targets for new drugs that antagonise these harmful effects.

What are the real applications (already being used on patients) of your work so far?

The applications used on patients do not usually come from the work of a single group, rather from many years of work by many different groups. Our group’s work is primarily focused on analysing the mechanisms that cause vascular damage in three adipokines (there are many more), which are two enzymes (dipeptidyl peptidase-4 and visfatin), and a pro-inflammatory cytokine (interleukin-1). In this sense, there are drugs on the market that are capable of inhibiting dipeptidyl peptidase-4 IV and are used to treat diabetes mellitus and whose effect on vascular disease is under study. There are also recombinant molecules and monoclonal antibodies that antagonise interleukin-1. Recent clinical trials suggest that the latter may be useful in the treatment of cardiovascular disease.

Can we talk about some remarkable developments we can look forward to in the near future?

We believe that drugs that are able to inhibit the effects of adipokines can have a beneficial effect on the arteries, delaying or even reversing vascular aging. We have experimental data pointing in that direction and we hope that in the coming years these promising data will be confirmed in appropriate clinical trials so that they can be applied in the general population.

Why do you think it is important that the scientific community in particular and society in general should focus its attention on longevity?

One of the most important characteristics of our society is its ageing population. We are living longer and in better conditions and we have more and more information about the aspects that favour longevity, both from a genetic and biological point of view as well as from an environmental and social point of view. In fact, one very important issue, in our opinion, is not only to prolong life, but above all to do so in the best physical, intellectual, psychological and social conditions. All of this requires the participation of different scientific and humanistic disciplines, as well as a global approach on the part of society as a whole.

In your opinion, what does a meeting like the Longevity World Forum mean and why did you decide to participate?

It is an opportunity to get to know different scientific, social, economic and ethical points of view, etc., on such an important subject as human ageing. It is also an opportunity to disseminate our work not only to the specialist scientific community, but to society at large.

Bruno Vellas

MD and PhD. Gerontopole University Hospital of Toulouse. Unit on Aging (France)

Bruno Vellas is chair of the Gerontopole & Department of Geriatric Internal Medicine at the Toulouse University Hospital and is member of INSERM UMR 1027, chair of the WHO Collaborating Center for Frailty, Clinical Research and Geriatric Training. He is of Chairman of the Scientific Committee of the plan Grand Age (National French Plan on Ageing). He studied medicine in Toulouse and received the degree of Doctor of Medicine in 1987 and a PhD in Pysiopathology in 1990. He had a doctoral training in nutrition and aging at the University of New Mexico, USA, Clinical Nutrition Lab, School of Medicine from 1987 to 1988. His main interests are: development of aging and geriatric clinical research and care. His research and care has been supported by several European, national and international research grants. He is the founder of the Gerontopole to develop innovation and research for older adults. He is the author and co-author of more than 858 publications in peer review journals since 1987, Index H: 81. He serves as editor, editorial committee member and reviewer of several major journals. He is adjunct professor at the Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA and is member of the scientific advisory board of several major scientific institutions in France, EU, Japan and the US. Since 2016, he is titular member of the French National Academy of Medicine, Officier de la Légion d’Honneur, and was recipient of the Palmes Académiques in 2016. He is the past president of the IAGG (International Association of Gerontology and Geriatrics) a NGO with a seat at the United Nations, and the founder of the EADC (European Alzheimer’s Disease Consortium), the CTAD (Clinical Trial in Alzheimer’s Disease conference) and the ICFSR (International Conference for Frailty and Sarcopenia Research). He is the chair of the WHO Collaborating Center for Frailty, Clinical Research and Geriatric Training since september 2017 and principal investigator on the INSPIRE Project on Geroscience.

Manuel Collado: “Our goal must be to reach an advanced age in a better state of health and to remain free of disease as long as possible”

Dr. Manuel Collado will be one of the speakers in the first session of #Longevity19, which will focus on will be one of the speakers in the first session of #Longevity19, which will focus on exploring longevity by presenting different research, from basic to applied, that is currently being carried out in this field. In this brief interview, he offers an insight to his perspective and to his work.

Why do you think it is important that the scientific community in particular and society in general should focus its attention on longevity?

Today’s society is characterised by the enormous increase in longevity experienced in recent decades. This increased longevity implies a radical change in the structure and composition of our society with major consequences, mainly in health. Aging is the main debilitating factor of our health and the ultimate cause of an enormous amount of diseases that lead to increased dependency and mortality. Addressing the basic mechanisms that contribute to ageing could provide us with new forms of prevention and treatment of the common bases of a large number of pathologies.

In your opinion, what does a meeting like the Longevity World Forum mean and why did you decide to participate?

The Longevity World Forum provides an exceptional opportunity to meet leading experts in the field of longevity and in the study of the fundamental aspects of ageing, a unique opportunity to learn at first hand the latest trends in this field, which are experiencing an enormous advance that could represent a radical change in the way we understand and approach this area of knowledge.

What should we understand by cellular senescence and what impact does it have on aging?

Cellular senescence is a process that is unleashed in the cells of the organism in response to damage experienced over time. As such, it plays a positive role in defending us from these aggressions; but as time goes by, these damaged cells accumulate in our tissues, damaging their normal function and even inducing changes that deteriorate their activity. Today we have sufficient evidence to affirm that this accumulation of senescent cells makes a significant contribution to a large number of so-called age-related diseases, and it has even been shown that eliminating them specifically improves the state of health at an advanced age in experimental animal models.

How do you think our life expectancy and our quality of life will evolve in the next decade?

Life expectancy has increased at a steady and sustained rate for more than a century now. There are discrepancies with regard to the possibility of exceeding a maximum age for the human population, and there are even those who dispute whether we can continue to increase average life expectancy even further. However, data shows us that our life expectancy is continuing to increase and that this greater longevity is always accompanied by a period of healthy living. “Our goal must be to reach an advanced age in a better state of health and to remain free of disease as long as possible.” But all this will only be possible with increased investment in both research and health.

What are you currently working on at CHUS and IDIS?

One of the main objectives of our IDIS laboratory is the study of cell senescence. We are interested in gaining a better understanding of this process: what its physiological functions are, how it contributes to pathologies, how we can alter them by increasing or eliminating senescent cells.

In your opinion, what has been the most important advance in the field of longevity since last year?

All the contributions of the various groups that have demonstrated beyond doubt how senescent cells contribute to very different pathologies associated with ageing and how it is possible to intervene therapeutically in them by selectively eliminating these cells.

Pedro Almaida

PhD. Chronobiology Group. Universidad de Murcia (Spain)

Graduate in Biology and PhD in Physiology from the University of Murcia. He worked for four years in the Molecular Nutrition Group of the Institute of Aquaculture at the University of Stirling (Scotland, United Kingdom) thanks to an extension grant for postdoctoral studies abroad from the Ramón Areces Foundation and an Intra-European Marie Curie grant to develop new fish models for the study of ageing, particularly the circadian system of these animals. He has been working since 2017 as a researcher in the Chronobiology Group of the University of Murcia on a project to understand the mechanisms associated with the ageing of the circadian system of vertebrate models (fish of the Nothobranchius genus), which connects environmental light, melatonin and the lipids that make up cell membranes, particularly mitochondria.

Carlos F. Sánchez-Ferrer

Professor of Pharmacology in Autonomous University of Madrid – FARMAVASM Group and IdiPAZ

Carlos Félix Sánchez Ferrer studied Medicine at the Universidad Autónoma de Madrid (UAM), where he graduated in 1981 and received his PhD in 1984. Having been awarded scholarships from the Spanish Health Research Fund (FIS) and the Mayo Foundation, he held a postdoctoral position during 1987 at the Mayo Clinic and Mayo Medical School (Dept. of Physiology), followed by another at the Medical College of Wisconsin (Dept of Physiology) thanks to an International Research Fellowship of the Fogarty International Center (National Institutes of Health, USA). He was a Lecturer in Pharmacology between 1987 and 2005 and has been Professor of this subject since 2005, always in the Department of Pharmacology and Therapeutics of the UAM. He has been the Director of this Department since 2013. He was Vice Dean of Research of the Faculty of Medicine of the UAM between 2000 and 2007 and has been Correspondent Academic of the National Royal Academy of Medicine of Spain since 2002. Together with Prof. Peiró, he leads a UAM and IdiPAZ research group named with the acronym FARMAVASM, dedicated to the study of the mechanisms that produce deterioration of the vascular function in pathological conditions, such as diabetes mellitus and obesity, as well as the analysis of the underlying cellular and molecular mechanisms of vascular aging. As pharmacologists, a fundamental aim of the group is to characterise new therapeutic targets that make it possible to prevent or delay vascular aging, using for this purpose different experimental approaches, from human vascular cell cultures to animal models and patient studies. He collaborates with various prestigious national and foreign researchers and has authored more than one hundred scientific publications in international journals, the majority in the first quartile. He has co-directed 18 doctoral theses and has been the lead researcher on 25 competitive projects at regional, national and international level.

Marc Ramis

Co-Founder and CEO of Senolytic Therapeutics, Inc. (Boston)

He is a co-founder and CEO at Senolytic Therapeutics Inc., a pharmaceutical company that develops a novel class of medicines by targeting senescence cells. He is also supporting investments and strategic partnerships at Life Biosciences Inc. in Europe. Currently, Marc is a strategic advisor at Ninevah Therapeutics, Cebiotex, Retinset Therapeutics and Origen Ventures. He is a co-founder and Partner at Chasing Science, an early-stage biomedical venture builder. Marc is also a founder and Advisor at Tech & Business Innovation (TBI), an academic firm focused on knowledge exchange and corporate-academic partnerships. Marc brings experience as advisor and board member for multiple organizations and as co-founder of several companies. Marc has implemented Entrepreneurs-in-Residence programs at several academic institutions such as IRB Barcelona. From 2010 to 2012, Marc was working for Isis Innovations/University of Oxford as an associate consultant in Spain and LATAM. From 2007 to 2011, Marc was working at Endor, a nanomedicine company based in Spain. During this period, he was R&D director (drug-delivery nano-systems for cancer therapy) and Business Development Director (launched several nanotechnology products to the cosmetic and textile markets).
Previously, Marc also worked in the pharmaceutical environment in Novartis. He also collaborated with other research institutions such as Cancer Research UK and Boston College during his academic career. Marc gained a DPhil in Biochemistry from the University of Oxford in 2006, and a Harvard Business School PLD Program in 2011. Marc also gained a M.Sc. in Chemical Engineering in 2001 and a B.Sc. in Chemistry from IQS (Barcelona) in 2000.

Manuel Serrano

PhD & ICREA professor – Institute Research in Biomedicine (Barcelona - Spain)

Manuel Serrano obtained his PhD in 1991, from the Universidad Autónoma de Madrid.  From 1991 to 1996, Serrano worked in the team of David Beach in Cold Spring Harbor Laboratory, NY.  During this period, Serrano made his most important discovery with the identification and characterization of the gene p16, one of the most important genes for anti-cancer protection.  Serrano returned to Spain in 1997 to lead a research group, first at the National Center of Biotechnology (CNB), and then, from 2003 to 2017, at the Spanish National Cancer Research Center (CNIO), both in Madrid.  In 2017, Serrano moved to the Institute for Research in Biomedicine (IRB), in Barcelona.

Manuel Serrano is internationally recognized in the field of tumor suppression.  In addition to the discovery of p16, one of his main discoveries has been the identification of cellular senescence as a main anti-oncogenic response. Recently, his laboratory has also shown that cellular senescence participates in several tissue remodeling processes during embryo development. The Serrano team was pioneer in the generation of genetically-modifed mice resistant to cancer and found a link between tumor suppressor genes and aging.

In recent years, the research interests of Manuel Serrano have extended to metabolism and cellular reprogramming in relation to aging.  The Serrano laboratory was first in demonstrating that cellular reprogramming into pluripotency is possible within an organism, and this discover was considered Advance of the Year 2013 by Nature Medicine. More recently, Serrano has reported in Science that in vivo reprogramming is enhanced by the coexistence of tissue injury thanks to the production of the interleukin IL-6. The focus of his laboratory is now to apply their knowledge on senescence and reprogramming to degenerative diseases such as lung, kidney and heart fibrosis.

Manuel Collado

Head of the Laboratory of Stem Cells in Cancer and Aging (Santiago de Compostela - Spain)

Manuel Collado holds a PhD in Biology from the Universidad Autónoma de Madrid. Having previously worked in London, New York and at the Spanish National Cancer Research Centre (CNIO) in Madrid, he is currently the Miguel Servet Researcher at the Health Research Institute of Santiago de Compostela (IDIS) where he manages the Cancer and Aging Stem Cell Laboratory. He publishes information on biomedical research into aging in the blog “Fuente de la Eterna Juventud”

Marc Ramis: “For the first time ever, we are treating age-associated diseases from mechanisms associated with senescence”

Dr. Marc Ramis defines himself as a passionate entrepreneur in the field of the so-called life sciences. For example, in the summer of 2017 and together with Dr. Manuel Serrano and other researchers, he embarked upon the creation of Senalytic Therapeutics, a company that develops innovative senolithic drugs, which are drugs based on cellular senescence. “We are facing many challenges because this is a new field. A great deal of uncertainty exists from the point of view of development, but given that we are living in an increasingly aging society, this is an area with a lot of future and a high impact. “For the first time ever, we are treating age-associated diseases from mechanisms associated with senescence”, he tells us.

Ramis explains that, for the time being, one can speak of brilliant academic and preclinical work. However, he qualifies this by saying that “right now we are experiencing a key moment in this sense”, given that all the knowledge surrounding the concept of cellular senescence is beginning to be transferred to the market. Moreover: Senalytic Therapeutics has plans to carry out the first systemic test on humans in 2020. Continuing with his words: “We will transfer the preclinical development data from this science to the clinical trial next year”.

All in all, cellular senescence has been gaining special prominence for some time now, as organisations such as Senalytic Therapeutics are demonstrating its direct relationship with different pathologies and aging. For example, their elimination or the reduction in their number is being related to the increase in life expectancy and the quality of life in patients with pulmonary fibrosis.

Dr. Marc Ramis will present the latest developments in this regard in the second edition of the Longevity World Forum. In particular, he will participate in the second session dedicated to R+D+i in longevity. “The differential value of this international congress is its social impact, because it serves as a forum for transmitting the concept of ageing to society,” he concludes.

Longevity World Forum

Longevity World Forum focuses its second edition on scientific innovation and healthy aging

The organisers of the Longevity World Forum, a pioneering congress at world level, have confirmed the thematic blocks for the contents of its second edition, which will take place on 14th and 15th November at the Palacio de Congresos (Conference Centre) of Valencia. Specifically, scientific innovation related to increased longevity and quality of life, as well as healthy aging, will be two of the main themes for the meeting in 2019.

Furthermore, the latest research currently underway in the field of longevity and the social and economic effects inherent to a society with an increasing life expectancy will be the other two subjects tackled during the two days, when internationally renowned professionals from the sectors involved in this matter will meet again.

The speakers will include, for example, Rafael de Cabo, chief of the Translational Gerontology Branch of the National Institute on Aging in Baltimore; Manuel Serrano, a doctor and professor who is currently working on the ICREA programme of the Institute for Research in Biomedicine of Barcelona (IRB Barcelona); and Álvaro Pascual-Leone, professor of Neurology at the Harvard Medical School, among others.

The Longevity World Forum has become established as the meeting point for the international scientific community, as well as for agents from academia and industry from different countries, whose work is closely related to increased life expectancy and healthy aging. The congress is supported by the Royal Academy of Medicine together with other public and private institutions of the bio-health and biotechnological sectors.