June 21, 2018
10:00 Jerry Shay, UT Southwestern (USA)
"Why measuring the shortest telomeres matter"
We developed TeSLA, Telomere Shortest Length Assay, which is a technique that detects telomeres (including those below one kilobase) from all chromosome ends. We measured the length of telomeres longitudinally in human peripheral blood mononuclear cells during human aging, in tissues during cancer progression, in telomere-related diseases, as well as in other organisms. The results indicate TeSLA is a robust method that improves the specificity and efficiency of telomere measurements, especially the shortest telomeres.
10:30 Helen M. Blau, Stanford Univ. (USA)
"The long and the short of it: telomere lengths predict cardiac failure"
Telomeres are DNA repeats that are protective caps at the ends of chromosomes and act as a biological clock for cell division. We have made the unexpected discovery that telomere shortening is a hallmark of cardiomyocytes in patients afflicted with genetic cardiomyopathies. Further, using iPSC technology, this shortening can be modeled in patient cardiomyocytes as they differentiate in culture. Sequelae of telomere shortening include induction of a DNA damage response and mitochondrial dysfunction. Telomeres now serve as novel targets for treating genetic cardiomyopathies.
11:00: Jérôme Feige, Nestlé Inst. of Health Sciences (CH)
"Aging disrupts the cross-talk between satellite cells and fibro-adipogenic progenitors during muscle regeneration"
11:45 Teresa Teixeira, IBPC, CNRS (FR)
"How telomeres determine replicative potential and senescence"
Telomeres provide a unique mechanism to limit the lifespan of eukaryotic cells through replicative senescence. To understand the flow of signalling events from telomeres to cell proliferation cessation, we set up a microfluidics-based live-cell imaging assay to investigate replicative senescence in individual yeast cell lineages following telomerase inactivation. Using this strategy, we identified contributors to senescence heterogeneity phenotype and discovered a major source of genomic instability operating in the course of senescence.
12:15 Stig Egil Bojesen, Copenhagen Univ. Hospital (DK)
"The long and the short of telomere length and morbidity and mortality"
I will be talking about telomere length as a marker and a cause of altered risk of diseases and mortality in the general population. Telomeres as the thread of fate determining health in humans is a tempting conception, but does it concur with the evidence? The talk will cover recent large scale human studies on telomere length and health and try to condense current knowledge, seen from a physician's point of view.
12:45 Lunch and Poster session (Abstract book available here)
14:15 Jessica Tyler, Weill Cornell Medicine (USA)
"An integrative analysis of replicative aging in budding yeast"
I will be presenting an integrative analysis of the replicative / mitotic aging process in budding yeast. Most recently, we have uncovered a global reduction in protein translation efficiency during aging, have identified the mechanistic basis for the reduction in translation and have manipulated the system further to extend lifespan.
14:45 George A. Garinis, IMBB, FORTH (GR)
"DNA damage and innate immune responses in development and disease"
Mammalian cells employ DNA damage and innate immune responses to allow injured cells to restore their damaged DNA template and communicate their compromised state to the surrounding milieu and eventually safeguard their bodily functions over time. However, in case of inborn defects in DNA repair or with ageing, DNA damage gradually builds up and chronic inflammation is established. The latter triggers the (premature) onset of age-related degeneration, metabolic defects and a battery of self-perpetuating pathological symptoms that may often threaten organism survival. Here, we will present evidence from mice carrying inborn defects in nucleotide excision repair pathway and discuss the beneficial and unrewarding outcomes of DNA damage-driven inflammation in the context of tissue-specific pathology and disease progression.
15:15 Vincent Dion, UNIL (CH)
"Contracting CAG/CTG repeats using the CRISPR-Cas9 nickase"
15:30 Jan Vijg, A. Einstein College of Medicine (USA)
"Genome instability and the limits to life span"
Genome instability, i.e., the tendency of the genome to undergo mutational changes in its information content, is a hallmark of aging. Mutations in somatic cells have been proposed as a major cause of aging at least since the 1950s, but this could never be tested because of a lack of sensitive methods. I will present data on age-related mutation accumulation in aging humans using new, single cell-based methodology and will discuss the possibility that the inherent instability of the somatic genome is not compatible with significant extension of the human life span.
16:30 Panel discussion (open to the public)
"To lengthen or not to lengthen: That is the question"
Manipulating telomere length to promote healthy aging
Moderator: John Furber
Discussants: Helen M. Blau
Stig E. Bojesen
18:00 John Grace Lecture (open to the public)
Helen M. Blau, Stanford Univ. (USA)
"Rejuvenation of muscle function: No pain, No gain"
June 22, 2018
9:30 Cynthia Kenyon, Calico (USA)
"Aging and rejuvenation in C. elegans"
I will be talking about pathways and gene networks that can slow the aging process and extend lifespan, and also about mechanisms that allow the animal to reverse hallmarks of aging during its normal life cycle.
10:00 Collin Ewald, ETHZ (CH)
"Transcriptiomic signature of longevity in C. elegans"
10:15 Johan Auwerx, EPFL (CH)
"Mitochondrial proteostasis in aging and age-related diseases"
By using a systems genetics approach applied to the BXD mouse genetic reference population (GRP) and validation studies in the nematode C. elegans, we identified a key role of mitochondrial protein homeostasis in the determination of lifespan across these different species. Modulation of mitochondrial proteostasis can be exploited therapeutically in the context of protein aggregation diseases, such as Alzheimer’s disease, and pharmacological inhibition of mitochondrial translation (by doxycycline) and/or NAD+ repletion (by dietary supplementation with NAD+ precursors) will reduce protein aggregates and improve clinical features in animal models of Alzheimer’s disease.
11:15 Vera Gorbunova, Univ. of Rochester (USA)
"Mechanisms of longevity in long-lived mammals"
Accumulation of mutations and epimutations is believed to contribute to aging process. But is more efficient repair and epigenome maintenance associated with longer lifespan? I will discuss new data focusing on the role of SIRT6 in regulation of DNA repair in short- and long-lived animals.
11:45 Andrea Komljenovic, UNIL (CH)
"Deciphering sex differences of the dynamic transcriptional signatures during D. melanogaster aging"
12:00 Tom Misteli, NIH (USA)
"Nuclear structure, aging and cancer"
The ultra-rare premature aging disorder Hutchinson Gilford Progeria Syndrome (HGPS), caused by mutation of an architectural protein of the cell nucleus, has become a paradigm for the path from gene discovery to elucidation of disease mechanisms and rapid development of therapeutic strategies. The disease shares numerous parallels with physiological aging and has provided novel insights into the basic biology of the human cell nucleus. Even the aspects that differ between HGSP and normal aging, such as the development of tumors, have been remarkably insightful.
13:30 Presentation of the Prix Henri Guenin
13:40 Stefanie Ginster, UNIL (CH)
"Control of non-melanoma skin cancers by PPARβ/δ"
13:55 James Kirkland, Mayo Clinic (USA)
"Cellular senescence, senolytics, chronic disease, and aging"
Interventions targeting mechanisms of aging hold promise for enhancing healthspan by delaying, preventing, or alleviating age-related diseases and conditions as a group, instead of one-at-a-time. Among these fundamental mechanisms is cellular senescence. Senescent cells, which are resistant to apoptosis, can secrete a range of pro-inflammatory cytokines and chemokines, matrix-destroying proteases, factors that cause stem cell dysfunction, and hemostatic factors, the senescence-associated secretory phenotype (SASP). We developed senolytic agents ‒ drugs that selectively eliminate senescent cells by inhibiting the pro-survival Senescent Cell Anti-apoptotic Pathways (SCAPs) that protect these cells from apoptosis due to their own SASP. Our studies show that intermittent administration of senolytic represents a new intervention that may delay, prevent, or treat multiple age- and chronic disease-related disorders.
14:25 Andrea Alimonti, IOR (CH)
"Cellular senescence" in aging and cancer: therapeutic opportunities"
My research is focused on the characterization of a novel type of cellular senescence — or aging — response that is elicited by complete loss of the tumor suppressor PTEN, and on the identification of novel compounds with pro-senescence activity. My aim is to develop the concept of pro-senescence therapy for cancer by identifying “pro-senescence” compounds for tumor cells.
14:55 Saul Villeda, UCSF (USA)
"Mechanisms of brain aging and rejuvenation"
A growing body of work has shown that systemic manipulations, such as heterochronic parabiosis and young blood administration, can partially reverse age-related cellular impairments and loss of cognitive faculties in the aged brain. I will discuss work from my research group that begins to provide mechanistic insight into the systemic and molecular drivers promoting rejuvenation in the aging brain.
15:25 Concluding remarks