Aging is characterized by a decline in the organism’s physiological integrity and vulnerability to disease. Although the consequences of aging on human health are broadly apparent, the causes and drivers of the aging process are just beginning to be understood. An important hallmark of aging 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.

A central goal of regenerative medicine is the ability to restore or rejuvenate tissues using stem cells. This approach relies on harnessing repair processes that have evolved to heal damaged tissues and to maintain tissue homeostasis. Immune modulation is an integral part of the process of tissue repair, and dysregulated immune responses are likely contributors to tissue dysfunction observed in old individuals. Age-associated inflammation, in particular, is likely an important roadblock for the success of regenerative therapies in aging. Thus, immune modulation aimed towards harnessing the anti-inflammatory function of immune cells to promote endogenous repair mechanisms is a promising strategy to improve regenerative success in older individuals. Ultimately, the success of regenerative therapies in age-related diseases depends on combined strategies targeted at overcoming these interacting roadblocks to tissue repair in aging.

Immune Modulation in Tissue Repair

Joana Neves’ team uses skeletal muscle regeneration as a paradigm of tissue repair to understand the molecular and cellular basis of the immune modulatory component of tissue regeneration and how its dysregulation in aging and disease can be targeted to optimize regenerative success. Our goal is to identify pathways that are used by immune cells to modulate the inflammatory tone of the tissue environment, with the goal of identifying new molecules with immune modulatory properties and therapeutic potential in regenerative medicine applied to old patients.

Stem Cell Aging

Pedro Sousa-Victor and his team use muscle aging as a model system to understand mechanisms of stem cell aging. 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).

2024-2026      AFM-Téléthon/ 140.000eur – “The contribution of immune aging to skeletal muscle regenerative failure”

2024-2029      European Research Council/ Consolidator Grant/ 1,998,842eur – 101126073 – immSC-AgingFate – “The Interplay of Aging, Immune Signaling and Stem Cell Function”

2023-2026      LaCaixa Foundation/ Health Research Grant/ 499,835eur – HR23-00881 – “Immune regulation of skeletal muscle metabolic health and exercise response in aging”

2024-2025      Breakthrough Idea Grant (iMM)/ 75.000eur – “Deciphering the failure of stem cell engraftment in aged organs”

2020-2024      European Molecular Biology Organization (EMBO)/ Installation Grant/ 250.000eur – IG4448 – “Mechanisms of tissue ageing and repair: roadblocks to stem cell-based therapies”

Sousa NS, Brás MF, Antunes IB, Lindholm P, Neves J**, Sousa-Victor, P**(2023). Aging disrupts MANF-mediated immune modulation during skeletal muscle regeneration. Nature Aging.

Sousa-Victor, P.**, García-Prat, L.** , Muñoz-Cánoves, P.** (2022).Control of satellite cell function in muscle regeneration and its disruption in ageing. Nature Reviews Molecular Cell Biology 23 (3), 204-226

Neves, J.**, Chirco, K.R., Cedron-Craft, W., Chew, S., Zhu, J., Jasper, H., and Lamba, D.A.** (2020). MANF delivery improves retinal homeostasis and cell replacement therapies in ageing mice. Experimental gerontology 134, 110893.

Munoz-Canoves P**, Neves J, Sousa-Victor P** (2020). Understanding muscle regenerative decline with aging: new approaches to bring back youthfulness to aged stem cells. FEBS Journal 287(3):406416.

Neves J**, Sousa-Victor P** (2020). Regulation of inflammation as an anti-aging intervention. FEBS Journal 287(2020):43–52.

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

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.

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

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.

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.

Neves J*, Demaria M*, Campisi J, Jasper H (2015) Of Flies, Mice, and Men: Evolutionarily Conserved Tissue Damage Responses and Aging. Developmental Cell 32(1):9-18.

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.

*equal contribution

**Corresponding author

2019 | Joana Neves | Sartorius & Science Prize for Regenerative Medicine & Cell Therapy

2019 | Pedro Sousa-Victor | Junior Leader Fellowship by “la Caixa” Foundation.

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

2017 | Joana Neves | Prize for best oral presentation at European Retina Meeting.

2016-2019 | Pedro Sousa-Victor | Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research.

2016-2017 | Joana Neves | Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research.

2015 | Pedro Sousa-Victor | La Vanguardia of Science Award to “Geriatric muscle stem cells switch reversible quiescence into senescence”.

2015 | Pedro Sousa-Victor | City of Barcelona award to “Geriatric muscle stem cells switch reversible quiescence into senescence”.

2013-2014 | Joana Neves | Glenn Foundation Postdoctoral Research Training Fellowship in the Biology of Aging, by Glenn Foundation for Medical Research.

2010 | Joana Neves | Postdoctoral Fellowship, by Science and Technology Foundation (FCT, Portugal).