Lisbon, Portugal • May 4-5, 2023
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Thursday, May 4 | 09:00 – 10:00 | Auditorium
Thursday, May 4 | 09:00 – 10:00 | Auditorium
Thursday, May 4 | 09:00 – 10:00 | Auditorium
Vision and Mission – establishing longevity medicine as a clinical department.
Thursday, May 4 | 10:20 – 10:40 | Auditorium
Thursday, May 4 | 10:40 – 11:20 | Auditorium
I will review recente progress in the study of the aging immune system with a focus on senescence and epigenetic regulation.
Thursday, May 4 | 10:40 – 11:20 | Auditorium
Thursday, May 4 | 11:20 – 11:40 | Auditorium
Thursday, May 4 | 11:40 – 12:00 | Auditorium
Thursday, May 4 | 12:00 – 12:20 | Auditorium
Thursday, May 4 | 14:00 – 15:00 | Auditorium
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
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
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 | 15:20 – 15:40 | Auditorium
Thursday, May 4 | 16:00 – 16:20 | Auditorium
The majority of proteins that evolved after appearance of multicellular life are glycosylated and glycans significantly affect structure and function of these proteins. However, due to structural complexity of glycans and the absence of a direct genetic template, the analysis of protein glycosylation is much more complicated than the analysis of DNA or proteins. Consequently, the knowledge about the importance of individual variation in glycans for both normal physiological processes and diseases is still limited. By generating glycomic data for over 150,000 individuals from some of the best characterized clinical and epidemiological cohorts we enabled glycomics to meet other ‘omics. Changes in glycosylation have been observed in numerous diseases, often even before other symptoms of a disease appeared, indicating that they may reflect early steps in the molecular pathophysiology of many complex diseases. Glycans are not only biomarkers, but also functional effectors that modulate protein function and initial data from intervention studies and animal models suggest that reversing changes in glycosylation may decrease the disease risk.
Thursday, May 4 | 17:20 – 17:40 | Auditorium
Background: Selenium and coenzyme Q10 are both important for optimal function of all living cells. It is known that a decreased level of either – or both – substances increases the risk for diseased patients. It is also known that the ageing process in the cardiovascular system results also in increased inflammation and oxidative stress. We wanted to evaluate if supplementation with selenium and CoQ10 could influence the ageing process of the cardiovascular system, and also mortality.
Methods: 443 elderly community living persons were included. On top of their usual medication, if any, they received selenium 200 micrograms/day, and coenzyme Q10 200 mg/day during 4 years. The follow-up time is now 12 years. Evaluations of cardiovascular mortality has been performed. As the ageing process is complex, we wanted to cover different aspects of the process. Therefore, we performed sub-analyzes involving endothelial dysfunction, inflammation, fibrosis, and apoptosis and metabolic profiles. We also evaluated expression of microRNA and different biomarkers involved in the ageing process. Finally, we analysed the telomere length of the chromosomes.
Results: Significant reduced cardiovascular mortality could be demonstrated in the active treatment group after 5 years, 10 years and 12 years. Highly significant differences in biomarkers for inflammation, fibrosis and apoptosis could be demonstrated. Significant differences in expression of microRNA, in metabolic profiles, but also in the length of telomeres could also be reported, and finally also regarding the “ageing” biomarkers.
Conclusion: The supplementation with selenium and coenzyme Q10 results in significantly reduced mortality that can be seen also after 12 years. This is the result of a complex mechanism in the body, where the ageing process of the cardiovascular system is central. All pointing in the direction, that in those who are low in selenium and coenzyme Q10, supplementation could slow down the accelerated ageing of the cardiovascular system that results. Finally, we could demonstrate reduced mortality also after 12 years as a result of the supplementation with selenium and coenzyme Q10.
Thursday, May 4 | 17:40 – 18:00 | Auditorium
The natural process of aging is accompanied by an increased incidence of chronic and acute diseases. Several key time-points in human life can determine the rates of tissue aging, directly impacting the pathophysiology of different diseases. This talk will highlight our research on in utero programming of human aging rates and impact on the development of different diseases, as well as highlight the critical role of mitochondria as one important regulator of the aging process and target for interventions to delay its related complications.
Friday, May 5 | 08:50 – 09:10 | Auditorium
Autophagy acts as a cytoplasmic rejuvenation mechanisms, implying that its enhancement has a marked geroprotective effect. Our group focuses on the identification of endogenous metabolites that stimulate autophagy, as well as on the identification of extracellular autophagy-inhibitory proteins (or ‘checkpoints’) the neutralization of which unblocks autophagy. Irrespective of their precise mode of action, autophagy enhancers have cytoprotective, anti-inflammatory and antifibrotic that combat aging and age-related pathologies. This applies to a variety of highly prevalent cardiovascular, neurodegenerative, malignant and metabolic diseases.
Friday, May 5 | 09:10 – 09:30 | Auditorium
While aging, your metabolism gradually slows down. As a result, your body absorbs fewer nutrients and lowers cell turnover. It may need help to cope with it. Precise nutrients and actives may slow damages to chromosome, improve function of mitochondria, protein quality, and other aspects of cellular integrity. Holistic Health are longevity supplements that goes beyond basic wellness support to target the complexity of health and aging mechanisms. We´ve been able to prove that they have a protective effect: they decrease telomere-shortening rate, an important hallmark of aging.
Friday, May 5 | 10:10 – 10:30 | Auditorium
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
Friday, May 5 | 11:30 – 11:50 | Auditorium
Hormesis is a wholistic approach to maintain, recover and enhance health, thus promoting healthy ageing and increased longevity. Any condition that induces low level stress inside the cells, and leads to the activation of one or more stress response defence pathways, is a potential hormetin. Physical, nutritional and mental hormetins initiate cellular stress responses and strengthen the homeodynamic space, robustness and resilience of an individual. Exercise, heat and irradiation are examples of physical hormetins, which activate heat shock-, DNA repair- and anti-oxidative-repsonses. Numerous nonnutritional chemical components in the food, such as flavonoids and polyphenols present in spices, herbs and other sources, are examples of nutritional hormetins, which induce anti-oxidative and anti-inflammatory stress responses. Calorie restriction and intermittent fasting are also hormetins, which activate the autophagic and sirtuin-mediated stress responses. Intense brain activity and focussed attention comprise mental hormetins. A combination of different hormetins can be the drugs for maintaining, improving and recovering health during ageing.
Friday, May 5 | 11:50 – 12:10 | Auditorium
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.
Friday, May 5 | 13:50 – 14:10 | Auditorium
Friday, May 5 | 14:10 – 14:30 | Auditorium
Friday, May 5 | 14:50 – 15:10 | Auditorium
Friday, May 5 | 15:10 – 15:30 | Auditorium
Friday, May 5 | 16:10 – 16:30 | Auditorium
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