A proteomic atlas of senescence-associated secretomes for aging biomarker development

PLoS Biology, Год журнала: 2020, Номер 18(1), С. e3000599 - e3000599

Опубликована: Янв. 16, 2020

The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. complexity the SASP, typically assessed by few dozen secreted proteins, been greatly underestimated, small set factors cannot explain diverse phenotypes it produces in vivo. Here, we present "SASP Atlas," comprehensive proteomic database soluble proteins exosomal cargo SASP originating senescence inducers cell types. Each profile consists hundreds largely distinct but also includes subset elevated all SASPs. Our analyses identify several candidate biomarkers cellular that overlap with aging markers human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), serine protease inhibitors (SERPINs), which significantly correlated age plasma cohort, Baltimore Longitudinal Study Aging (BLSA). findings will facilitate identification characteristic catalog potential assess burden, stimulus, tissue origin senescent cells

Язык: Английский

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Targeting the progression of chronic kidney disease

Nature Reviews Nephrology, Год журнала: 2020, Номер 16(5), С. 269 - 288

Опубликована: Фев. 14, 2020

Язык: Английский

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Connective tissue growth factor (CTGF) from basics to clinics

Matrix Biology, Год журнала: 2018, Номер 68-69, С. 44 - 66

Опубликована: Март 21, 2018

Язык: Английский

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Therapy-Induced Senescence: An “Old” Friend Becomes the Enemy

Cancers, Год журнала: 2020, Номер 12(4), С. 822 - 822

Опубликована: Март 29, 2020

For the past two decades, cellular senescence has been recognized as a central component of tumor cell response to chemotherapy and radiation. Traditionally, this form senescence, termed Therapy-Induced Senescence (TIS), was linked extensive nuclear damage precipitated by classical genotoxic chemotherapy. However, number other forms therapy have also shown induce in cells independently direct genomic damage. This review attempts provide comprehensive summary both conventional targeted anticancer therapeutics that vitro vivo. Still, utility promoting therapeutic endpoint remains under debate. Since represents durable growth arrest, it might be argued is desirable outcome cancer therapy. accumulating evidence suggesting capacity escape from TIS would support an alternative conclusion, provides avenue whereby can evade potentially lethal action drugs, allowing enter temporary state dormancy eventually facilitates disease recurrence, often more aggressive state. Furthermore, now strongly connected remodeling, dormancy, acquiring ominous malignant phenotypes accounts for several untoward adverse effects Here, we argue barrier effective treatment, discuss emerging efforts identify exploit agents with senolytic properties strategy elimination persistent residual surviving population, goal mitigating tumor-promoting influence senescent thereby reduce likelihood relapse.

Язык: Английский

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Senolytics prevent mt-DNA-induced inflammation and promote the survival of aged organs following transplantation

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Авг. 27, 2020

Older organs represent an untapped potential to close the gap between demand and supply in organ transplantation but are associated with age-specific responses injury increased immunogenicity, thereby aggravating transplant outcomes. Here we show that cell-free mitochondrial DNA (cf-mt-DNA) released by senescent cells accumulates aging augments immunogenicity. Ischemia reperfusion induces a systemic increase of cf-mt-DNA promotes dendritic cell-mediated, inflammatory responses. Comparable events observed clinically, levels elevated older deceased donors, isolated capable activating human cells. In experimental models, treatment old donor animals senolytics clear diminish release, dampening immune prolonging survival cardiac allografts comparable young organs. Collectively, identify accumulating as key factor inflamm-aging present approach improve outcomes availability.

Язык: Английский

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Wnt signaling pathway in aging-related tissue fibrosis and therapies

Ageing Research Reviews, Год журнала: 2020, Номер 60, С. 101063 - 101063

Опубликована: Апрель 6, 2020

Язык: Английский

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Klotho, Oxidative Stress, and Mitochondrial Damage in Kidney Disease

Antioxidants, Год журнала: 2023, Номер 12(2), С. 239 - 239

Опубликована: Янв. 20, 2023

Reducing oxidative stress stands at the center of a prevention and control strategy for mitigating cellular senescence aging. Kidney disease is characterized by premature aging syndrome, to find modulator targeting against stress, mitochondrial dysfunction, in kidney cells could be great significance prevent progression this disease. This review focuses on pathogenic mechanisms related appearance damage dysfunction In scenario, anti-aging Klotho protein plays crucial role modulating signaling pathways involving manganese-containing superoxide dismutase (Mn-SOD) transcription factors FoxO Nrf2, known antioxidant systems, other function regulators, such as uncoupling 1 (UCP1), B-cell lymphoma-2 (BCL-2), Wnt/β-catenin, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 alpha), factor EB, (TFEB), (PPAR-gamma). Therefore, postulated very promising new target future therapeutic strategies mitochondria abnormalities, patients.

Язык: Английский

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The multifaceted benefits of walking for healthy aging: from Blue Zones to molecular mechanisms

GeroScience, Год журнала: 2023, Номер 45(6), С. 3211 - 3239

Опубликована: Июль 26, 2023

Abstract Physical activity, including walking, has numerous health benefits in older adults, supported by a plethora of observational and interventional studies. Walking decreases the risk or severity various outcomes such as cardiovascular cerebrovascular diseases, type 2 diabetes mellitus, cognitive impairment dementia, while also improving mental well-being, sleep, longevity. Dose-response relationships for walking duration intensity are established adverse outcomes. Walking’s favorable effects on factors attributed to its impact circulatory, cardiopulmonary, immune function. Meeting current physical activity guidelines briskly 30 min per day 5 days can reduce several age-associated diseases. Additionally, low-intensity exercise, exerts anti-aging helps prevent age-related making it powerful tool promoting healthy aging. This is exemplified lifestyles individuals Blue Zones, regions world with highest concentration centenarians. other activities contribute significantly longevity these regions, being an integral part their daily lives. Thus, incorporating into routines encouraging walking-based interventions be effective strategy aging all populations. The goal this review provide overview vast consistent evidence supporting specific focus discuss outcomes, prevention Furthermore, will delve molecular cellular mechanisms aging, providing insights underlying biological through which beneficial effects.

Язык: Английский

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Discovering small-molecule senolytics with deep neural networks

Nature Aging, Год журнала: 2023, Номер 3(6), С. 734 - 750

Опубликована: Май 4, 2023

Язык: Английский

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Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis

European Heart Journal, Год журнала: 2019, Номер 41(31), С. 2983 - 2996

Опубликована: Дек. 4, 2019

Abstract Inflammation is a hallmark and potent driver of pathological vascular remodelling in atherosclerosis. However, current anti-inflammatory therapeutic strategies have shown mixed results. As an alternative perspective on the conundrum chronic inflammation emerging evidence points towards small subset senescent cells as critical player central node driving Senescent belonging to various cell types are dominant source large array pro-inflammatory cytokines additional plaque destabilizing factors, being involved with aspects atherosclerosis pathogenesis. Antagonizing these key agitators local instability may provide causative multi-purpose strategy treat Anti-senescence treatment options translational potential currently development. several questions challenges remain be addressed before novel approaches enter clinical setting.

Язык: Английский

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