Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Language: Английский

---

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches

Cell, Journal Year: 2022, Volume and Issue: 185(2), P. 379 - 396.e38

Published: Jan. 1, 2022

The liver is the largest solid organ in body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of healthy and obese human murine combining single-cell CITE-seq, single-nuclei sequencing, transcriptomics, proteomics. By integrating these multi-omic datasets, provide validated strategies to reliably discriminate localize all hepatic cells, including population lipid-associated macrophages (LAMs) at bile ducts. We then align this across seven species, revealing conserved program bona fide Kupffer cells LAMs. also uncover respective spatially resolved cellular niches microenvironmental circuits driving their unique transcriptomic identities. demonstrate that LAMs are induced by local lipid exposure, leading induction steatotic regions liver, while cell development crucially depends on cross-talk with stellate via evolutionarily ALK1-BMP9/10 axis.

Language: Английский

---

Liver tumour immune microenvironment subtypes and neutrophil heterogeneity

Nature, Journal Year: 2022, Volume and Issue: 612(7938), P. 141 - 147

Published: Nov. 9, 2022

Language: Английский

---

Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease

Immunity, Journal Year: 2021, Volume and Issue: 54(8), P. 1883 - 1900.e5

Published: July 30, 2021

Language: Английский

---

Immune cell-mediated features of non-alcoholic steatohepatitis

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 22(7), P. 429 - 443

Published: Nov. 5, 2021

Non-alcoholic fatty liver disease (NAFLD) includes a range of hepatic manifestations, starting with steatosis and potentially evolving towards non-alcoholic steatohepatitis (NASH), cirrhosis or even hepatocellular carcinoma. NAFLD is major health burden, its incidence increasing worldwide. Although it primarily disturbed metabolism, involves several immune cell-mediated inflammatory processes, particularly when reaching the stage NASH, at which point inflammation becomes integral to progression disease. The cell landscape diverse steady state further evolves during NASH direct consequences for severity. In this Review, we discuss current concepts related role cells in onset NASH. A better understanding mechanisms by contribute pathogenesis should aid design innovative drugs target therapeutic options are limited. (NASH) serious chronic disorder prevalence Metabolic nature, also mobilizes system. Here, Huby Gautier knowledge regarding how subsets affect progression.

Language: Английский

---

Macrophages in health and disease

Cell, Journal Year: 2022, Volume and Issue: 185(23), P. 4259 - 4279

Published: Nov. 1, 2022

Language: Английский

---

Hepatic inflammatory responses in liver fibrosis

Nature Reviews Gastroenterology & Hepatology, Journal Year: 2023, Volume and Issue: 20(10), P. 633 - 646

Published: July 3, 2023

Language: Английский

---

Immune mechanisms linking metabolic injury to inflammation and fibrosis in fatty liver disease – novel insights into cellular communication circuits

Journal of Hepatology, Journal Year: 2022, Volume and Issue: 77(4), P. 1136 - 1160

Published: June 22, 2022

Language: Английский

---

Tissue-specific macrophages: how they develop and choreograph tissue biology

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

---

Dynamic Shifts in the Composition of Resident and Recruited Macrophages Influence Tissue Remodeling in NASH

Cell Reports, Journal Year: 2021, Volume and Issue: 34(2), P. 108626 - 108626

Published: Jan. 1, 2021

Macrophage-mediated inflammation is critical in the pathogenesis of non-alcoholic steatohepatitis (NASH). Here, we describe that, with high-fat, high-sucrose-diet feeding, mature TIM4pos Kupffer cells (KCs) decrease number, while monocyte-derived Tim4neg macrophages accumulate. In concert, infiltrating enter liver and consist a transitional subset that expresses Cx3cr1/Ccr2 second characterized by expression Trem2, Cd63, Cd9, Gpmnb; markers ascribed to lipid-associated (LAMs). The Cx3cr1/Ccr2-expressing macrophages, referred as C-LAMs, localize macrophage aggregates hepatic crown-like structures (hCLSs) steatotic liver. C-motif chemokine receptor 2 (Ccr2)-deficient mice, C-LAMs fail appear liver, this prevents hCLS formation, reduces LAM numbers, increases fibrosis. Taken together, our data reveal dynamic changes subsets during NASH link these shifts pathologic tissue remodeling.

Language: Английский

---