Geriatric muscle stem cells switch reversible quiescence into senescence

  title={Geriatric muscle stem cells switch reversible quiescence into senescence},
  author={Pedro Sousa‐Victor and Susana Gutarra and Laura Garcia-Prat and Javier Rodr{\'i}guez-Ubreva and Laura Ortet and Vanessa Ruiz-Bonilla and Merc{\`e} Jard{\'i} and Esteban Ballestar and Susana Gonz{\'a}lez and Antonio L. Serrano and Eusebio Perdiguero and Pura Mu{\~n}oz-C{\'a}noves},
Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and that this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by… 

Geroconversion of aged muscle stem cells under regenerative pressure

How cellular senescence may be a common mechanism of stem cell aging at the organism level is discussed and induction of p16INK4a in young muscle stem cells through deletion of the Polycomb complex protein Bmi1 recapitulates the geriatric phenotype is shown.

Ageing: Genetic rejuvenation of old muscle

Pura Munoz-Canoves and colleagues show that ageing satellite cells undergo an irreversible transition from quiescence to a pre-senescence state associated with increased expression of p16INK4a, a tumour-suppressor protein that has been identified as a marker for senescence.

Autophagy maintains stemness by preventing senescence

It is reported that basal autophagy is essential to maintain the stem-cell quiescent state in mice and revealed to be a decisive stem- cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.

Assessing Autophagy in Muscle Stem Cells

Two strategies for assessing autophagic activity in satellite cells from GFP-LC3 reporter mice are described, which allows direct autophagosome labeling, or from non-transgenic (wild-type) mice, where Autophagosomes can be immunostained, allowing a relatively rapid assessment of autophagy in stem cells from skeletal muscle in homeostasis and in different pathological scenarios such as regeneration, aging or disease.

Rejuvenating Muscle Stem Cell Function: Restoring Quiescence and Overcoming Senescence.

A unifying hypothesis posits that in aging humans, first loss of quiescence occurs, depleting the stem cell population, but that remaining SMSCs are increasingly subject to presenescence in the very old.

How stem cells manage to escape senescence and ageing – while they can

  • M. Ricchetti
  • Biology
    BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2016
Genetic, pharmacological, and pharmacological correction of defective autophagy reverses satellite cell senescence and restores muscle regeneration in geriatric mice, with perspectives of modulating age‐related functional decline of muscle.

Satellite cells in ageing: use it or lose it

This review examines how periodic activation and cycling of satellite cells through exercise can mitigate senescence acquisition and myogenic decline in aged muscle.

FoxO maintains a genuine muscle stem-cell quiescent state until geriatric age.

Tissue regeneration declines with ageing but little is known about whether this arises from changes in stem-cell heterogeneity. Here, in homeostatic skeletal muscle, we identify two quiescent

Control of satellite cell function in muscle regeneration and its disruption in ageing

The role and regulation of satellite cells in skeletal muscle homeostasis and regeneration is discussed, including the cell-intrinsic control of quiescence versus activation, the importance of satellite cell–niche communication, and deregulation of these mechanisms associated with ageing.



Functional dysregulation of stem cells during aging: a focus on skeletal muscle stem cells

The current literature on the coordinated relationship between cell extrinsic and intrinsic factors that regulate the function of satellite cells, and ultimately determine tissue homeostasis and repair during aging, is reviewed to encourage the search for new anti‐aging strategies.

Maintenance of muscle stem cell quiescence by microRNA-489

Evidence is provided of the miRNA pathway in general, and of a specific miRNA, miR-489, in actively maintaining the quiescent state of an adult stem-cell population, as it functions as a regulator of satellite-cell quiescence.

Skeletal muscle stem cells: effects of aging and metabolism on muscle regenerative function.

Recent and emerging insights into the molecular and biochemical signals that control satellite cell function are reviewed and discussed in the context of muscle degenerative diseases such as dystrophy and sarcopenia.

Satellite cells and the muscle stem cell niche.

For the last half century, the advance of molecular biology, cell biology, and genetics has greatly improved the understanding of skeletal muscle biology, with focuses on functions of satellite cells and their niche during the process ofletal muscle regeneration.

Molecular regulation of stem cell quiescence

Deciphering the molecular mechanisms regulating adult stem cell quiescence will increase the understanding of tissue regeneration mechanisms and how they are dysregulated in pathological conditions and in ageing.

Stem-cell ageing modified by the cyclin-dependent kinase inhibitor p16INK4a

It is reported that the cyclin-dependent kinase inhibitor p16INK4a accumulates and modulates specific age-associated HSC functions, and may ameliorate the physiological impact of ageing on stem cells and thereby improve injury repair in aged tissue.