The Brain-body Energy Conservation Model of Aging DOI Open Access
Evan D. Shaulson, Alan A. Cohen, Martin Picard

и другие.

Опубликована: Ноя. 24, 2023

Aging involves seemingly paradoxical changes in energy metabolism. Molecular damage accumulation increases cellular expenditure, yet whole-body expenditure is stable or decreases with age. We resolve this apparent contradiction by positioning the brain as mediator and broker economy of within organism. As somatic tissues accumulate over time, costly intracellular stress responses are activated, causing aging/senescent cells to secrete cytokines that convey increased demand (hypermetabolism) brain. To conserve face a shrinking budget, deploys conservation responses, which suppress low priority processes, producing fatigue, physical inactivity, blunted sensory capacities, immune alterations, endocrine “deficits”. term cascade Brain-body Energy Conservation (BEC) model aging. The BEC outlines i) energetic cost aging, ii) how perception senescence-associated hypermetabolism may drive manifestations iii) principles underlying modifiability aging trajectories stressors geroscience interventions.

Язык: Английский

Mitochondrial dysfunction: mechanisms and advances in therapy DOI Creative Commons

Zong Yao,

Hao Li, Peng Liao

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Май 15, 2024

Abstract Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation disease progression. Particularly, mitochondrial dysfunctions identified many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, cancer. However, the multifaceted nature elusive phenotypic threshold dysfunction complicate our understanding contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among most important therapeutic targets. In recent years, strategies targeting have continuously emerged transitioned clinical trials. Advanced intervention such as using healthy replenish or replace damaged mitochondria, has shown promise preclinical trials various Mitochondrial components, mtDNA, mitochondria-located microRNA, associated proteins can be potential agents augment function immunometabolic diseases tissue injuries. Here, we review current knowledge pathophysiology concrete examples We also summarize treat perspective dietary supplements targeted therapies, well translational situation related pharmacology agents. Finally, this discusses innovations applications transplantation an advanced promising treatment.

Язык: Английский

Процитировано

213
The senescence-associated secretory phenotype and its physiological and pathological implications DOI
Boshi Wang, Jin Han, Jennifer H. Elisseeff

и другие.

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(12), С. 958 - 978

Опубликована: Апрель 23, 2024

Язык: Английский

Процитировано

136
Biomarkers of cellular senescence and risk of death in humans DOI Creative Commons
Jennifer L. St. Sauver,

Susan A. Weston,

Elizabeth J. Atkinson

и другие.

Aging Cell, Год журнала: 2023, Номер 22(12)

Опубликована: Окт. 6, 2023

Abstract A robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators age‐related pathology, components the senescence associated (SASP) have been studied as biomarkers cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations candidate biomarkers, including chemokines, cytokines, matrix remodeling proteins, growth factors, could predict mortality older adults. We assessed associations between plasma levels 28 SASP proteins risk over median follow‐up 6.3 years 1923 patients 65 age or with zero one chronic condition at baseline. Overall, five strongly an increased death were GDF15, RAGE, VEGFA, PARC, MMP2, after adjusting for age, sex, race, presence condition. The combination clinical demographic covariates exhibited significantly higher c‐statistic (0.79, 95% confidence interval (CI): 0.76–0.82) than alone (0.70, CI: 0.67–0.74) ( p < 0.001). Collectively, these findings lend further support cellular informative predictors clinically important health outcomes adults, death.

Язык: Английский

Процитировано

39
Proteomic aging clock (PAC) predicts age‐related outcomes in middle‐aged and older adults DOI Creative Commons
Chia‐Ling Kuo,

Zhiduo Chen,

Peiran Liu

и другие.

Aging Cell, Год журнала: 2024, Номер 23(8)

Опубликована: Май 15, 2024

Abstract Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features biological might, therefore, offer useful information for the testing and, ultimately, clinical use gerotherapeutics. We aimed to develop a proteomic clock (PAC) all‐cause mortality risk as proxy age. Data were from UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 70 years 2923 plasma proteins assessed using Olink Explore 3072 assay®. 10.9% died during mean follow‐up 13.3 years, with age at death 70.1 years. The Spearman correlation PAC chronological was 0.77. showed robust age‐adjusted associations predictions onset various diseases in general disease‐free participants. associated deviation enriched several processes related hallmarks aging. Our results expand previous findings by showing that acceleration, based on PAC, strongly predicts incident disease outcomes. Particularly, it facilitates evaluation multiple conditions population, thereby, contributing prevention initial diseases, which vary among individuals may subsequently lead additional comorbidities.

Язык: Английский

Процитировано

15
Activation of senescence in critically ill patients: mechanisms, consequences and therapeutic opportunities DOI Creative Commons
Paula Martín-Vicente, Cecilia López‐Martínez, Beatriz Rioseras

и другие.

Annals of Intensive Care, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 5, 2024

Abstract Whereas aging is a whole-organism process, senescence cell mechanism that can be triggered by several stimuli. There increasing evidence critical conditions activate programs irrespective of patient’s age. In this review, we briefly describe the basic pathways and consequences their activation in critically ill patients. The available suggests paradigm which beneficial short term rendering cells resistant to apoptosis, but also detrimental late phase inducing pro-inflammatory pro-fibrotic state. Senescence therapeutic target. use drugs eliminate senescent (senolytics) or senescence-associated phenotype (senomorphics) will require monitoring these responses identification windows improve outcome

Язык: Английский

Процитировано

8
Blood mitochondrial health markers cf-mtDNA and GDF15 in human aging DOI Creative Commons
Caroline Trumpff,

Qiuhan Huang,

Jeremy Michelson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 31, 2025

Abstract Altered mitochondria biology can accelerate biological aging, but scalable biomarkers of mitochondrial health for population studies are lacking. We examined two potential candidates: 1) cell-free DNA (cf-mtDNA), a marker signaling elevated with disease states accessible as distinct entities from plasma or serum; and 2) growth differentiation factor 15 (GDF15), an established biomarker aging downstream energy transformation defects stress signaling. In cohort 430 participants aged 24-84 (54.2% women), we measured serum cf-mtDNA, GDF15 levels at timepoints 5 years apart, then assessed their associations age, BMI, diabetes, sex, health-related behaviors, psychosocial factors. As expected, showed positive, exponential association age (r=0.66, p<0.0001) increased by 33% over five years. cf-mtDNA was not correlated age. BMI sex were also related to nor GDF15. Type 2 diabetes only positively associated Exploring drivers systemic signaling, report novel linking higher education lower age-adjusted (r=-0.14, p<0.0034), both baseline the 5-year follow up, highlighting influence factors on health. Overall, our findings among adults spanning six decades lifespan establish between GDF15, emerging Further needed determine if blood metabolic be moderated behaviors.

Язык: Английский

Процитировано

1
Senescent alveolar type II epithelial cells-secreted GDF15 promotes silicosis progression via interfering intercellular communication DOI Creative Commons

Wenxiu Lian,

Demin Cheng,

Wenqing Sun

и другие.

Ecotoxicology and Environmental Safety, Год журнала: 2025, Номер 292, С. 117917 - 117917

Опубликована: Фев. 21, 2025

Язык: Английский

Процитировано

1
The brain–body energy conservation model of aging DOI
Evan D. Shaulson, Alan A. Cohen, Martin Picard

и другие.

Nature Aging, Год журнала: 2024, Номер 4(10), С. 1354 - 1371

Опубликована: Окт. 8, 2024

Язык: Английский

Процитировано

7
Psychobiological regulation of plasma and saliva GDF15 dynamics in health and mitochondrial diseases DOI Creative Commons

Qiuhan Huang,

Caroline Trumpff, Anna S. Monzel

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 21, 2024

Abstract GDF15 (growth differentiation factor 15) is a marker of cellular energetic stress linked to physical-mental illness, aging, and mortality. However, questions remain about its dynamic properties measurability in human biofluids other than blood. Here, we examine the natural dynamics psychobiological regulation plasma saliva four studies representing 4,749 samples from 188 individuals. We show that protein detectable (8% concentration), likely produced by salivary glands secretory duct cells. Using brief laboratory socio-evaluative stressor paradigm, find psychosocial increases (+3.5-5.9%) (+43%) with distinct kinetics, within minutes. Moreover, exhibits robust awakening response, declining ∼40-89% 30-45 minutes peak level at time waking up. Clinically, individuals genetic mitochondrial OxPhos diseases elevated baseline GDF15, post-stress levels both correlate multi-system disease severity, exercise intolerance, subjective experience fatigue. Taken together, our data establish dynamic, sensitive psychological states, clinically relevant endocrine diseases. These findings also point shared pathway integrating metabolic mental stress.

Язык: Английский

Процитировано

4
Increased Pretransplant Inflammatory Biomarkers Predict Death With Function After Kidney Transplantation DOI
Elizabeth C. Lorenz, Byron H. Smith,

Yun Liang

и другие.

Transplantation, Год журнала: 2024, Номер 108(12), С. 2434 - 2445

Опубликована: Июнь 24, 2024

Chronic systemic inflammation is associated with mortality in patients chronic kidney disease, cardiovascular and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, FAS, factor-α, interleukin-15, interleukin-1β) death function (DWF) after transplantation (KT).

Язык: Английский

Процитировано

4