Lisbon, Portugal • May 4-5, 2023


Thursday, May 4  | 12:00 – 12:20 | Auditorium

The Role of Telomeres in Aging

by Maria A. Blasco, PhD, Scientific Director of the Spanish National Cancer Research Centre (CNIO), Madrid, Spain

Thursday, May 4  | 14:00 – 15:00 | Auditorium

Quantification of Biological Aging

by Daniel W. Belsky, Assistant Professor of Epidemiology, The Robert N. Buttler Columbia Aging Center , Columbia University, New York, USA

Biological aging is the progressive loss of system integrity that occurs with advancing age, undermining the integrity and resilience of tissues and organ systems and driving vulnerability to disease, disability, and death. Animal experiments suggest that biological aging is is caused by an accumulation of cellular-level molecular changes, sometimes referred to as hallmarks, that, when slowed or reversed, result in increased healthy lifespan. Human translation of therapies to modify hallmarks of aging and extend healthy lifespan is a critical priority for an aging global population. To speed this translation, measurements that quantify the progress and pace of biological aging in humans are needed. The past several years have seen rapid progress toward this goal, with measurements based on micro-array assays of DNA methylation marks representing the current state of the art. My talk will review progress and challenges in this effort, share some of our work to develop a DNA methylation biomarker of the pace of biological aging, DunedinPACE, and report results from biological aging analysis of the CALERIE Trial, a randomized controlled trial of caloric restriction in healthy, non-obese midlife humans.

Thursday, May 4  | 14:00 – 15:00 | Auditorium

Telomeres and Biology of Aging

by Fabrizio d’Adda di Fagagna, PhD, Principal Investigator of Institute of Molecular Genetics (CNR), Pavia, Italy

Cell aging, also known as cellular senescence, was first demonstrated to be caused by telomere shortening and dysfunction. It is now well stablished that short and damaged telomeres are associated, often in a causative manner, with several age-related severe human diseases and aging itself. Nevertheless, so far we lacked the means to blunt the consequences of telomere dysfunction. We will discuss an innovative approach, presently in preclinical development, effective in a variety of animal models of accelerated aging and age-related disorders.

Thursday, May 4  | 14:00 – 15:00 | Auditorium

Toward Clinical Evaluation of mTOR inhibitors to Target Biological Aging

by Matt Kaeberlein, PhD, Professor of Genome Sciences, University of Washington, Seattle, WA, USA

The mechanistic Target of Rapamycin (mTOR) is an evolutionarily conserved regulator of longevity that plays a central role linking environmental cues to aging biology. The mTOR inhibitor rapamycin is currently the most effective and reproducible pharmacological approach to extending lifespan in animals. Several groups have independently shown that short-term treatment with rapamycin in mice can prevent age-related decline or rejuvenate functional measures of health in various organs and tissues including brain, heart, kidney, muscle, oral cavity, immune system, and ovary. Multiple clinical trials have been, or will soon be, initiated with the goal to determine whether rapamycin can positively impact age-related endpoints in humans and companion dogs. Several hundred “biohackers” are proactively using rapamycin off-label in hopes that it will increase healthspan and lifespan and a growing number of medical practitioners are prescribing rapamycin for such “off-label” use.

Thursday, May 4  | 16:40 – 17:00 | Auditorium

Big data and the science of ageing

by João Pedro Magalhães, Principal Investigator, Genomics of Ageing and Rejuvenation Lab, Birmingham, UK

Age-related conditions are the leading causes of death and healthcare costs. Retarding the ageing process would have enormous medical and financial benefits. A large number of genes and drugs extending lifespan in model organisms already exist, yet given long validation times, only a small fraction of them can be explored for humans clinical applications. Therefore, prioritizing drugs and gene targets is imperative. In this talk, I will present big data and machine learning approaches for predicting longevity genes and compounds, which we validated experimentally. I will also present integrative, multi-dimensional approaches that provide insights into longevity pathways and their role in age-related diseases. Overall, our data-driven approaches allow us to identify and prioritize further compounds with potential healthy longevity properties.

Thursday, May 4  | 17:00 – 17:20 | Auditorium

Fundamental Biomedical Research, Interdisciplinary and Longevity

by Cláudia Cavadas, Vice Rector, Research, University of Coimbra, Director of the Institute of Interdisciplinary Research, University of Coimbra , Head of the Neuroendocrinology and Aging Group, Center for Neuroscience and Cell Biology of the University of Coimbra (CNC-UC), Coimbra, Portugal

Friday, May 5  | 10:10 – 10:30 | Auditorium

The Use of Autologous Stem Cells in Regenerative Medicine. cGMP Stem Cell Banking

by Elena Rusyn, PhD, Chief Scientific Officer at American Cell Technology, Sunrise, Florida, USA

Stem cell therapy and research are offering new benefits to patients with limited treatment options offered through traditional methods. Regenerative medicine centers all over the world are working on different cell types to meet this need. Selecting a suitable cell type and tissue source for human clinical applications in the field of regenerative and anti-aging medicine is an important challenge. The ethics issues around the embryonic cells tumor formation, and rejection make it a less interesting candidate for clinical applications. Other sources of stem cells are induced pluripotent stem cells (iPS cells). There are still several issues on the processes adopted to produce the iPS cells from adult stem cells for therapeutic purposes that limit their utility. In sharp contrast, progress with adult stem cells has been impressive. Since mesenchymal stem cells (MSCs) can be easily harvested from the adipose tissue and can also be cultured and expanded in vitro they have become a good target for tissue regeneration. They have a broader differentiation capacity than previously thought, since they give rise to cell types of multiple tissues. The continuing debate here is about what cells, allogeneic or autologous, are the safer option for clinical applications. Over the past few decades, allogeneic stem cells have been recognized as good sources of stem cells for transplantation. However, despite several advantages and the high therapeutic potential of this approach, there are important concerns related to long-term side effects, regulatory-compliance, immunogenic response and infection incidence rates. In contrast, cell-based therapies based on autologous cells derived from adipose tissue offer exceptional high safety profile and clinical outcomes.

Friday, May 5  | 10:30 – 10:50 | Auditorium

Prevention is the best therapy – The role of genetics

by Dr. Stefanie Wendel, Medical Manager of Prevention Division, CeGaT GmbH, Tübingen, Germany

Friday, May 5  | 11:50 – 12:10 | Auditorium

Understanding senescence heterogeneity and preclinical development of FOXO4-DRI peptides against a “scarred” subtype

by Peter de Keizer, PhD, Associate Professor, Senescence in Cancer and Aging at Utrecht University, Utrecht, Netherlands

Senescent cells are associated with chronic disease and cancer metastases in human and were shown to be drivers thereof in. For instance, we have shown before that interference with FOXO4-p53 through cell penetrating peptides could selectively eliminate senescent cells in mouse models where senescence is enhanced through defective DNA-damage repair (Baar .. de Keizer, Cell, 2017). Doing so could restore some signs of homeostasis. There have been many attempts towards development of compounds to eliminate senescent cells, but with varying success. At least in part, this is because of a lack of understanding of the different aspects of senescence. At the summit, I will discuss how we identified that what we call senescence, is in fact a range of phenotypes. Through multiplex characterization, we identified there is considerable heterogeneity even within the same population of senescent cells. I will provide examples and zoom a damaged type of senescence, which we call now call “scarred” senescence, a subtype characterized both by FOXO4/PML and a modified form of p53, i.e. phosphorylated on Ser46. I will show that at least for this type of senescence, we have been able to apply new structural and biomolecular insights to progressively develop potent therapeutics, i.e. compounds CL04177 and CL04183. I will now show in more detail how this may be particularly true for scarred senescent and cancer cells. From a translational point of view, I will show how human cancer cells in patients, in vitro, in 3D organoids and in vivo can present a state of scarring and thereby provide in ideal target disease for testing the efficacy of scarring-targeting FOXO4 peptides. Moreover, I will show how CL04177 potently counters metastases in vivo at dosing scheme and frequency that are well below the Maximally Tolerated Dose and applicable for preclinical translation. Together, this argues we should better define senescence subtypes and focus on specific therapeutics. Scarred senescence can especially be targeted by FOXO4-based peptides, with a translational potential to the clinic.