Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles

Sahu, Amrita; Clemens, Zachary; Shinde, Sunita; Sivakumar, Sruthi; Pius, Abish; Bhatia, Ankit; Picciolini, Silvia; Carlomagno, Cristiano; Gualerzi, Alice; Bedoni, Marzia; Houten, Bennett Van; Lovalekar, Mita; Fitz, Nicholas F.; Lefterov, Iliya; Barchowsky, Aaron; Koldamova, Radosveta; Ambrosio, Fabrisia

doi:10.1038/s43587-021-00143-2

Cited by 68 publications

(44 citation statements)

References 61 publications

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“…It is shown that blood therapy involves several different anti-ageing factors (GDF11 [ 20 ], GPLD1 [ 21 ], clusterin [ 22 ], Klotho [ 23 ], etc.). On the one hand, it leads to controversy [ 19 ], but on the other hand, it also suggests that greater benefits may be achieved by synchronizing multiple factors to combat ageing.…”

Section: The Characteristics Of Ageing and Their Potential For Transl...mentioning

confidence: 99%

“…The youthful secretory phenotype is a newly proposed hypothesis. It aims to generalize the anti-ageing factors (including GDF11, GPLD1, clusterin, Klotho, NAD + , eNAMPT, GSTM2, exosomes, et al) found in young blood and in the secretome of young cells [ 20 , 21 , 22 , 23 , 49 , 51 , 57 ]. These “young factors (existing in young blood as well as being secreted by a heterogeneous subgroup of ageing cells)” may dilute or inhibit “old factors” promoting ageing, thus playing a rejuvenating role [ 14 , 15 ].…”

Section: Strategies For Reversing Senescence and The Potential Underl...mentioning

confidence: 99%

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Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming

Chen

Skutella

2022

Cells

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In this review, we seek a novel strategy for establishing a rejuvenating microenvironment through senescent cells specific reprogramming. We suggest that partial reprogramming can produce a secretory phenotype that facilitates cellular rejuvenation. This strategy is desired for specific partial reprogramming under control to avoid tumour risk and organ failure due to loss of cellular identity. It also alleviates the chronic inflammatory state associated with ageing and secondary senescence in adjacent cells by improving the senescence-associated secretory phenotype. This manuscript also hopes to explore whether intervening in cellular senescence can improve ageing and promote damage repair, in general, to increase people’s healthy lifespan and reduce frailty. Feasible and safe clinical translational protocols are critical in rejuvenation by controlled reprogramming advances. This review discusses the limitations and controversies of these advances’ application (while organizing the manuscript according to potential clinical translation schemes) to explore directions and hypotheses that have translational value for subsequent research.

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Section: The Characteristics Of Ageing and Their Potential For Transl...mentioning

confidence: 99%

Section: Strategies For Reversing Senescence and The Potential Underl...mentioning

confidence: 99%

Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming

Chen

Skutella

2022

Cells

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“…Mice overexpressing α-Klotho have increased lifespan, enhanced cognition, delayed age-related vascular dysfunction, decreased diabetes-related inflammation, and improved skeletal muscle regeneration. 27 , 28 , 29 As α-Klotho holds therapeutic potential, various strategies to increase α-Klotho have been proposed. However, despite extensive effort there are few approaches for increasing or restoring α-Klotho that are either feasible to advance into clinical trials or that have shown efficacy in trials.…”

Section: Introductionmentioning

confidence: 99%

Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans

et al. 2022

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“…Factors activating Notch, growth differentiation factor 11 (GDF11), and tissue inhibitor of metalloproteinases 2 (TIMP-2), on the other hand, have been suggested to have rejuvenating effects ( Castellano et al, 2017 ; Conboy et al, 2005 ; Conboy and Rando, 2002 ; Mahmoudi et al, 2019 ), although the role of GDF11 is still controversial ( Egerman et al, 2015 ; Egerman and Glass, 2019 ; Harper et al, 2016 ; Schafer et al, 2016 ; Sinha et al, 2014 ). In addition, transcript levels of the prolongevity protein Klotho in circulating extracellular vesicles decrease with aging ( Sahu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

Mashinchian

Hong

Michaud

et al. 2022

eLife

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Sustained exposure to a young systemic environment rejuvenates aged organisms and promotes cellular function. However, due to the intrinsic complexity of tissues it remains challenging to pinpoint niche-independent effects of circulating factors on specific cell populations. Here we describe a method for the encapsulation of human and mouse skeletal muscle progenitors in diffusible polyethersulfone hollow fiber capsules that can be used to profile systemic aging in vivo independent of heterogeneous short-range tissue interactions. We observed that circulating long-range signaling factors in the old systemic environment lead to an activation of Myc and E2F transcription factors, induce senescence and suppress myogenic differentiation. Importantly, in vitro profiling using young and old serum in 2D culture does not capture all pathways deregulated in encapsulated cells in aged mice. Thus, in vivo transcriptomic profiling using cell encapsulation allows for the characterization of effector pathways of systemic aging with unparalleled accuracy.

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Regulation of aged skeletal muscle regeneration by circulating extracellular vesicles

Cited by 68 publications

References 61 publications

Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming

Synergistic Anti-Ageing through Senescent Cells Specific Reprogramming

Orally-active, clinically-translatable senolytics restore α-Klotho in mice and humans

In vivo transcriptomic profiling using cell encapsulation identifies effector pathways of systemic aging

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