bims-caglex 2024-08-11 papers

Issue of 2024‒08‒11
four papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Mech Ageing Dev. 2024 Aug 05. pii: S0047-6374(24)00076-9. [Epub ahead of print] 111976

Senescence of skeletal stem cells and their contribution to age-related bone loss.

Eva M Wölfel, Paula Fernandez-Guerra, Mikkel Ørnfeldt Nørgård, Shakespeare Jeromdesella, Pernille Kirkegaard Kjær, Anna Sofie Elkjær, Moustapha Kassem, Florence Figeac.

Human aging is linked to bone loss, resulting in bone fragility and an increased risk of fractures. This is primarily due to an age-related decline in the function of bone-forming osteoblastic cells and accelerated cellular senescence within the bone microenvironment. Here, we provide a detailed discussion of the hypothesis that age-related defective bone formation is caused by senescence of skeletal stem cells, as they are the main source of bone forming osteoblastic cells and influence the composition of bone microenvironment. Furthermore, this review discusses potential strategies to target cellular senescence as an emerging approach to treat age-related bone loss.

Keywords: Cellular senescence; age-related bone disease; marrow stromal stem cells; skeletal stem cells

DOI: https://doi.org/10.1016/j.mad.2024.111976

Sci China Life Sci. 2024 Aug 02.

Gut microbiota and healthy longevity.

Jia Luo, Shan Liang, Feng Jin.

Recent progress on the underlying biological mechanisms of healthy longevity has propelled the field from elucidating genetic modification of healthy longevity hallmarks to defining mechanisms of gut microbiota influencing it. Importantly, the role of gut microbiota in the healthy longevity of the host may provide unprecedented opportunities to decipher the plasticity of lifespan on a natural evolutionary scale and shed light on using microbiota-targeted strategies to promote healthy aging and combat age-related diseases. This review investigates how gut microbiota affects healthy longevity, focusing on the mechanisms through which gut microbiota modulates it. Specifically, we focused on the ability of gut microbiota to enhance the intestinal barrier integrity, provide protection from inflammaging, ameliorate nutrientsensing pathways, optimize mitochondrial function, and improve defense against age-related diseases, thus participating in enhancing longevity and healthspan.

Keywords: bile acids; gut microbiota; healthy aging; longevity; short-chain fatty acids; tryptophan metabolites

DOI: https://doi.org/10.1007/s11427-023-2595-5

Cell Metab. 2024 Aug 06. pii: S1550-4131(24)00277-8. [Epub ahead of print]36(8): 1795-1805.e6

Intermittent clearance of p21-highly-expressing cells extends lifespan and confers sustained benefits to health and physical function.

A key challenge in aging research is extending lifespan in tandem with slowing down functional decline so that life with good health (healthspan) can be extended. Here, we show that monthly clearance, starting from 20 months, of a small number of cells that highly express p21Cip1 (p21high) improves cardiac and metabolic function and extends both median and maximum lifespans in mice. Importantly, by assessing the health and physical function of these mice monthly until death, we show that clearance of p21high cells improves physical function at all remaining stages of life, suggesting healthspan extension. Mechanistically, p21high cells encompass several cell types with a relatively conserved proinflammatory signature. Clearance of p21high cells reduces inflammation and alleviates age-related transcriptomic signatures of various tissues. These findings demonstrate the feasibility of healthspan extension in mice and indicate p21high cells as a therapeutic target for healthy aging.

Keywords: aging; cellular senescence; frailty; inflammation; morbidity compression

DOI: https://doi.org/10.1016/j.cmet.2024.07.006

Biochim Biophys Acta Mol Cell Res. 2024 Aug 03. pii: S0167-4889(24)00149-6. [Epub ahead of print]1871(7): 119806

Artificial mitochondrial transplantation (AMT) reverses aging of mesenchymal stromal cells and improves their immunomodulatory properties in LPS-induced synoviocytes inflammation.

Lynda Bourebaba, Nabila Bourebaba, Larry Galuppo, Krzysztof Marycz.

Nowadays, regenerative medicine techniques are usually based on the application of mesenchymal stromal cells (MSCs) for the repair or restoration of injured damaged tissues. However, the effectiveness of autologous therapy is limited as therapeutic potential of MSCs declines due to patient's age, health condition and prolonged in vitro cultivation as a result of decreased growth rate. For that reason, there is an urgent need to develop strategies enabling the in vitro rejuvenation of MSCs prior transplantation in order to enhance their in vivo therapeutic efficiency. In presented study, we attempted to mimic the naturally occurring mitochondrial transfer (MT) between neighbouring cells and verify whether artificial MT (AMT) could reverse MSCs aging and improve their biological properties. For that reason, mitochondria were isolated from healthy donor equine adipose-derived stromal cells (ASCs) and transferred into metabolically impaired recipient ASCs derived from equine metabolic syndrome (EMS) affected horses, which were subsequently subjected to various analytical methods in order to verify the cellular and molecular outcomes of the applied AMT. Mitochondria recipient cells were characterized by decreased apoptosis, senescence and endoplasmic reticulum stress while insulin sensitivity was enhanced. Furthermore, we observed increased mitochondrial fragmentation and associated PARKIN protein accumulation, which indicates on the elimination of dysfunctional organelles via mitophagy. AMT further promoted physioxia and regulated autophagy fluxes. Additionally, rejuvenated ASCs displayed an improved anti-inflammatory activity toward LPS-stimulated synoviocytes. The presented findings highlight AMT as a promising alternative and effective method for MSCs rejuvenation, for potential application in autologous therapies in which MSCs properties are being strongly deteriorated due to patients' condition.

Keywords: AMT; ASCs; Aging; EMS; Immunomodulation; Senescence

DOI: https://doi.org/10.1016/j.bbamcr.2024.119806