Back to agendaABSTRACT
Speakers: ICREA Research Professors Pura Muñoz (UPF) and Prof. Manuel Serrano (IRB Barcelona)
When: 9th of October 2018, 18:00h
Where: ICREA, Pg. Lluís Companys 23, 6th floor
Abstracts:
Pura Muñoz
New approaches to bring back youthfulness to aged stem cells
Aging is a nearly universal process affecting all tissues. Despite its constancy in our lives, aging remains mysterious at a fundamental level. Nevertheless, common hallmarks of aging across different species have been proposed offering an integrated view of the basic mechanisms of aging. Primary hallmarks include cell autonomous changes linked to epigenetic alterations, genomic instability, telomere attrition and loss of proteostasis (protein homeostasis), which are followed by antagonistic responses such us deregulated nutrient sensing, altered mitochondrial function and cellular senescence. Aging hallmarks converge in the exhaustion of stem cells, which provokes tissue regenerative decline. Skeletal muscle provides a stark example of this decline. Its stem cells sustain muscle regeneration throughout life but at advanced age they fail for largely undefined reasons. Several causes for this age-associated stem cell regenerative failure are emerging: decline in proteostatic quality-control mechanisms, metabolic alterations, entry into senescence and changes in the systemic (circulatory) environment. I will review our recent findings on how to improve the regenerative capacity of old stem cells by countering these age-associated alterations, with the ulterior idea that the aging process is malleable and that it is feasible to rejuvenate aged cells and tissues.
Manuel Serrano
Senescence as a new therapeutic target to treat ageing-related diseases
A major advance in the field of ageing research has been the demonstration that senescent cells play a key role in aging and, even more importantly, the discovery of small pharmacological compounds that can kill senescent cells within the organism resulting in improved health. Upon tissue damage or stress, a substantial fraction of cells respond by adopting a cellular state known as “senescence”. Regardless of their initial cell identity, senescent cells share key properties; namely, global chromatin remodelling, robust proliferation blockade, and a massive pro-inflammatory secretome. The initial biological purpose of senescent cells is to orchestrate tissue repair, ultimately leading to their own disposal by the immune system and to their replacement by new, functional cells. This is the favorable, beneficial, face of cellular senescence. However, in certain contexts that are generally associated with chronic damage, degenerative processes, or organismal ageing, tissue repair is inefficient and senescent cells are not cleared. Indeed, senescent cells accumulate in many human pathologies including various fibrotic diseases, atherosclerosis, and neurodegenerative diseases. This is the detrimental, pathological, face of cellular senescence. Importantly, the last few years have witnessed the identification of small compounds that preferentially kill senescent cells, termed senolytic drugs. Such senolytic treatments in mice show an unprecedented therapeutic effect on the aforementioned diseases including lung fibrosis, atherosclerosis, and neurodegenerative diseases. I will present our contributions to the understanding of cellular senescence both in tissue repair and in pathological contexts.
The ICREA colloquia are a great way to learn about remote fields of research from our best experts. We usually have two speakers, who offer their opinions on the same subject from very different angles. Open to all ICREAs and their guests.
