Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung

  title={Sentinel p16INK4a+ cells in the basement membrane form a reparative niche in the lung},
  author={Nabora S Reyes and Maria Krasilnikov and Nancy C. Allen and Jin Young Lee and Ben Hyams and Minqi Zhou and Supriya Ravishankar and Monica Cassandras and Chaoqun Wang and Imran Khan and Peri Matatia and Yoshikazu Johmura and Ari B. Molofsky and Michael Matthay and Makoto Nakanishi and Dean Sheppard and Judith Campisi and Tien Peng},
Senescent cells are recognized drivers of aging-related decline in organ function, but deciphering the biology of senescence in vivo has been hindered by the paucity of tools to track and isolate senescent cells in tissues1–4. Deleting senescent cells from transgenic murine models have demonstrated therapeutic benefits in numerous age-related diseases5–11, but the identity, behavior, and function of the senescent cells deleted in vivo remain elusive. We engineered an ultra-sensitive reporter of… 

Multiparametric senescent cell phenotyping reveals CD24 osteolineage cells as targets of senolytic therapy in the aged murine skeleton

These studies provide a new approach using multiplexed protein profiling by CyTOF to define senescent mesenchymal cells in vivo and identify a highly inflammatory, senescent CD24+ osteolineage population cleared by senolytics.

Senescent Cells in IPF: Locked in Repair?

Data from chemo-resistant tumors demonstrated re-entry of senescent cells and their reprogramming into cancer stem cells and novel single cell RNA sequencing analyses of lung repair identified activation of the senescence program in stem cell-like repair cells in mice, and question whether the term “senescence” is still appropriate.

Efficacy and limitations of senolysis in atherosclerosis

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IL-1 and senescence: Friends and foe of EGFR neutralization and immunotherapy

Classic and recent findings about the cellular processes driving senescence and SASP are summarized, and a state-of-the-art of the anti-cancer strategies available so far that exploits the activation and/or blockade of senescences-based mechanisms are provided.

Intersection of Inflammation and Senescence in the Aging Lung Stem Cell Niche

This review will attempt to address the “chicken or the egg” question as to whether senescence drives inflammation in the aging lung, or vice versa, and whether the causality of this relationship has therapeutic implications for age-related lung diseases.

Senescent fibroblasts support lung repair

  • P. Strzyz
  • Biology, Medicine
    Nature Reviews Molecular Cell Biology
  • 2022
Reyes et al. show that fibroblasts with properties of cellular senescence are present in healthy epithelial tissues and — by upregulating the senescence associated secretory phenotype (SASP) — they

Regenerative Medicine and the Hope for a Cure.

Human Hair Graying is Naturally Reversible and Linked to Stress

This work develops an approach to quantitatively profile natural graying events and their associated proteomic signatures along individual human hairs, resulting in a quantifiable physical timescale of aging and provides a new model to examine the modifiability of human aging.

Quantitative mapping of human hair greying and reversal in relation to life stress

The results show how quantitatively mapping HPPs in humans can provide an opportunity to examine the modifiability of biological aging in relation to life exposures and a threshold-based mechanism for the episodic instability of HF pigmentation and the temporary reversibility of graying.



Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence

A reporter allele is described, p16tdTom, enabling the in vivo identification and isolation of cells featuring high-level activation of the p16INK4a promoter, displaying characteristics of senescence.

Naturally occurring p16Ink4a-positive cells shorten healthy lifespan

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Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders

Data indicate that cellular senescence is causally implicated in generating age-related phenotypes and that removal of senescent cells can prevent or delay tissue dysfunction and extend healthspan.

Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice

It is demonstrated that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells, demonstrating that senolytic drugs may represent a new class of radiation mitigators and anti-aging agents.

A biomarker that identifies senescent human cells in culture and in aging skin in vivo.

It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.

The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs

The results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.