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Ageing & Tissue Repair – Stem Cell Ageing

Ageing is characterized by a decline in the organism’s physiological integrity and vulnerability to disease. Although the consequences of ageing on human health are broadly apparent, the causes and drivers of the ageing process are just beginning to be understood. An important hallmark of ageing is the loss of regenerative capacity that results from age-related changes in the systemic environment and the niche, as well as intrinsic limitations of stem cells themselves. Thus, the success of regenerative therapies in age-related diseases depends on combined strategies targeted at overcoming these interacting roadblocks to tissue repair in ageing.

In the Sousa-Victor Lab we use muscle ageing as a model system to understand mechanisms of stem cell ageing. We are currently working on three main research lines that aim to integrate knowledge of intrinsic mechanisms that drive stem cell loss of function with age (i) with immune-derived signaling in muscle regenerative responses (ii) to devise combinatorial approaches for improving the success stem-cell based therapies applied to the sarcopenic muscle (iii).

The Sousa-Victor lab is part of the Ageing & Tissue Repair joint lab, running two independent, complementary and cooperative research programs led by two group leaders: The research program in Sousa-Victor Lab aims to understand intrinsic limitations of aged stem cells. The Neves lab is focused on inflammatory signaling in ageing and immune modulatory strategies to improve regenerative success. Our goal is to apply the insights from the study of alterations in the ageing immune environment and stem cell ageing to develop new stem cell-based therapies to improve the health of old individuals. By studying stem cell function and immune modulatory mechanisms in an integrated manner, rather than as independent problems in the biology of tissue repair, we aim to provide a better understanding of the problems and optimized strategies for stem-cell based therapies in aging.

The Ageing & Tissue Repair joint lab uses Drosophila and in vitro models as platforms for screening, discovery and mechanistic studies, which are then translated into functional studies using mouse models and validated in human samples.

Research Team

Inês Antunes
Lab Manager
ines.antunes@medicina.ulisboa.pt

Neuza Sousa
MSc Student
neuza.sousa@medicina.ulisboa.pt

Research Areas

  • Mechanisms of intrinsic stem cell ageing
  • Modulation of stem cell function by immune derived factors
  • Stem cell-based therapies in sarcopenia

Ongoing Research Projects

2019/2022 la Caixa Junior Leader Fellowship, Incoming Program - New mechanisms driving stem cell ageing

Awards

2019 – Junior Leader Fellowship by la Caixa Foundation

2018 – Prize of Best Scientific work to “MANF is an evolutionary conserved anti-gernonic factor” at Bay Area Aging meeting, UC Berkley

2016-2019 Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research

2015 La Vanguardia of Science Award to “Geriatric muscle stem cells switch reversible quiescence into senescence”

2015 City of barcelona award to “Geriatric muscle stem cells switch reversible quiescence into senescence”

2006 PhD Fellowship by Fundação para a Ciência e Tecnologia (FCT, Portugal)

Selected Publications

Joana Neves, Pedro Sousa‐Victor (2019) Regulation of inflammation as an anti‐aging intervention. FEBS J. Sep 16. doi: 10.1111/febs.15061. [Epub ahead of print].

Sousa-Victor P*, Neves, J*, Cedron-Craft, W, Ventura, PB, Liao, CY, Riley, RR, Soife, I, van Bruggen, N, Kolumam, GA, Villeda, SA, Lamba DA, Jasper H (2019) MANF regulates metabolic and immune homeostasis in ageing and protects against liver damage. Nature Metabolism 1: 276–290

Sousa-Victor P**, Jasper H, Neves J** (2018) Trophic Factors in Inflammation and Regeneration: The Role of MANF and CDNF. Frontiers in physiology 9: 1629

Sousa-Victor P, Garcia-Prat L, Munoz-Canoves P (2018) New mechanisms driving muscle stem cell regenerative decline with aging. The International journal of developmental biology 62: 583-590

Sousa-Victor P, Ayyaz A, Hayashi R, Qi Y, Madden DT, Lunyak VV, Jasper H (2017) Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells. Cell Reports 20: 2527-2537

Garcia-Prat L*, Sousa-Victor P*, Munoz-Canoves P (2017) Proteostatic and Metabolic Control of Stemness. Cell stem cell 20: 593-608

Neves J*, Sousa-Victor P*, Jasper H (2017) Rejuvenating Strategies for Stem Cell-Based Therapies in Aging. Cell stem cell 20: 161-175

Neves J, Zhu J, Sousa-Victor P, Konjikusic M, Riley R, Chew S, Qi Y, Jasper H, Lamba DA (2016) Immune modulation by MANF promotes tissue repair and regenerative success in the retina. Science 353: aaf3646

Sousa-Victor P, Garcia-Prat L, Serrano AL, Perdiguero E, Munoz-Canoves P (2015) Muscle stem cell aging: regulation and rejuvenation. Trends in endocrinology and metabolism: TEM 26: 287-296

Sousa-Victor P, Gutarra S, Garcia-Prat L, Rodriguez-Ubreva J, Ortet L, Ruiz-Bonilla V, Jardi M, Ballestar E, Gonzalez S, Serrano AL, Perdiguero E, Munoz-Canoves P (2014) Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506: 316-321

Perdiguero E, Sousa-Victor P, Ruiz-Bonilla V, Jardi M, Caelles C, Serrano AL, Munoz-Canoves P (2011) p38/MKP-1-regulated AKT coordinates macrophage transitions and resolution of inflammation during tissue repair. The Journal of Cell Biology 195: 307-322

*equal contribution

**Corresponding author

group leader :
Pedro Sousa-Victor