scholarly journals Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans

2021 ◽  
Author(s):  
Ineke Dhondt ◽  
Clara Verschuuren ◽  
Aleksandra Zecic ◽  
Tim Loier ◽  
Bart Braeckman ◽  
...  
Keyword(s):  
Close Association ◽  
Muscle Architecture ◽  
Biological Age ◽  
Automated Image Analysis ◽  
Systematic Screening ◽  
C Elegans ◽  
Age Related ◽  
Gfp Reporter ◽  
Reporter Strains

Sarcopenia encompasses a progressive decline in allover muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the strong commonalities with human muscle structure and the facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical assessment relies on visual scoring of muscle architecture, which is subjective and inaccurate. To resolve this, we have developed an automated image analysis pipeline for the detailed quantification and classification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter strains. We then extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed us to establish a general linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted RNAi-mediated knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and will be of use for systematic screening for pharmacological or genetic modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.

scholarly journals Prediction of biological age by morphological staging of sarcopenia in Caenorhabditis elegans

2021 ◽  
Author(s):  
Ineke Dhondt ◽  
Clara Verschuuren ◽  
Aleksandra Zečić ◽  
Tim Loier ◽  
Bart P. Braeckman ◽  
...  
Keyword(s):  
Close Association ◽  
Visual Assessment ◽  
Muscle Architecture ◽  
Biological Age ◽  
Progressive Decline ◽  
C Elegans ◽  
Age Related ◽  
Gfp Reporter ◽  
The Relationship ◽  
Microscopy Images

Sarcopenia encompasses a progressive decline in muscle quantity and quality. Given its close association with aging, it may represent a valuable healthspan marker. Given the commonalities with human muscle structure and facile visualization possibilities, C. elegans represents an attractive model for studying the relationship between sarcopenia and healthspan. However, classical visual assessment of muscle architecture is subjective and has low throughput. To resolve this, we have developed an image analysis pipeline for the quantification of muscle integrity in confocal microscopy images from a cohort of aging myosin::GFP reporter worms. We extracted a variety of morphological descriptors and found a subset to scale linearly with age. This allowed establishing a linear model that predicts biological age from a morphological muscle signature. To validate the model, we evaluated muscle architecture in long-lived worms that are known to experience delayed sarcopenia by targeted knockdown of the daf-2 gene. We conclude that quantitative microscopy allows for staging sarcopenia in C. elegans and may foster the development of image-based screens to identify modulators that mitigate age-related muscle frailty and thus improve healthspan in C. elegans.

scholarly journals Biological Age Prediction From Wearable Device Movement Data Identifies Nutritional and Pharmacological Interventions for Healthy Aging

2021 ◽  
Vol 2 ◽  
Author(s):  
Rebecca L. McIntyre ◽  
Mizanur Rahman ◽  
Siva A. Vanapalli ◽  
Riekelt H. Houtkooper ◽  
Georges E. Janssens
Keyword(s):  
Healthy Aging ◽  
Machine Learning Algorithms ◽  
Biological Age ◽  
Wearable Device ◽  
Biological Aging ◽  
Accelerometer Data ◽  
Pharmacological Interventions ◽  
C Elegans ◽  
Movement Data ◽  
Age Related

Intervening in aging processes is hypothesized to extend healthy years of life and treat age-related disease, thereby providing great benefit to society. However, the ability to measure the biological aging process in individuals, which is necessary to test for efficacy of these interventions, remains largely inaccessible to the general public. Here we used NHANES physical activity accelerometer data from a wearable device and machine-learning algorithms to derive biological age predictions for individuals based on their movement patterns. We found that accelerated biological aging from our “MoveAge” predictor is associated with higher all-cause mortality. We further searched for nutritional or pharmacological compounds that associate with decelerated aging according to our model. A number of nutritional components peak in their association to decelerated aging later in life, including fiber, magnesium, and vitamin E. We additionally identified one FDA-approved drug associated with decelerated biological aging: the alpha-blocker doxazosin. We show that doxazosin extends healthspan and lifespan in C. elegans. Our work demonstrates how a biological aging score based on relative mobility can be accessible to the wider public and can potentially be used to identify and determine efficacy of geroprotective interventions.

scholarly journals Senotherapeutic peptide reduces skin biological age and improves skin health markers

2020 ◽  
Author(s):  
Alessandra Zonari ◽  
Lear E. Brace ◽  
Kallie Z. Al-Katib ◽  
William F. Porto ◽  
Daniel Foyt ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Skin Aging ◽  
Dermal Fibroblasts ◽  
Ultraviolet B ◽  
Biological Age ◽  
Chronological Aging ◽  
C Elegans ◽  
Age Related ◽  
Etoposide Treatment ◽  
Screening Platform

AbstractSkin aging has been primarily related to aesthetics and beauty. Therefore, interventions have focused on reestablishing skin appearance, but not necessarily skin health, function, and resilience. Recently, cellular senescence was shown to play a role in age-related skin function deterioration and influence organismal health and, potentially, longevity. In the present study, a two-step screening was performed to identify peptides capable of reducing cellular senescence in human dermal fibroblasts (HDF) from Hutchinson-Gilford Progeria (HGPS) patients. From the top four peptides of the first round of screening, we built a 764-peptide library using amino acid scanning, of which the second screen led to the identification of peptide 14. Peptide 14 effectively decreased HDF senescence induced by HGPS, chronological aging, ultraviolet-B radiation, and etoposide treatment, without inducing significant cell death, and likely by modulating longevity and senescence pathways. We further validated the effectiveness of peptide 14 using human skin equivalents and skin biopsies, where peptide 14 promoted skin health and reduced senescent cell markers, as well as the biological age of samples, according to the Skin-Specific DNA methylation clock, MolClock. Topical application of peptide 14 outperformed Retinol treatment, the current gold-standard in “anti-aging” skin care. Finally, we determined that peptide 14 is safe for long-term applications and also significantly extends both the lifespan and healthspan of C. elegans worms tested in two independent testings. This highlights the potential for geroprotective applications of the senotherapeutic compounds identified using our screening platform beyond the skin.

scholarly journals Two human metabolites rescue a C. elegans model of Alzheimer’s disease via a cytosolic unfolded protein response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Priyanka Joshi ◽  
Michele Perni ◽  
Ryan Limbocker ◽  
Benedetta Mannini ◽  
Sam Casford ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Unfolded Protein Response ◽  
Neurodegenerative Disorders ◽  
C Elegans ◽  
Unfolded Protein ◽  
Model Of Alzheimer’S Disease ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
Protein Response

AbstractAge-related changes in cellular metabolism can affect brain homeostasis, creating conditions that are permissive to the onset and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases. Although the roles of metabolites have been extensively studied with regard to cellular signaling pathways, their effects on protein aggregation remain relatively unexplored. By computationally analysing the Human Metabolome Database, we identified two endogenous metabolites, carnosine and kynurenic acid, that inhibit the aggregation of the amyloid beta peptide (Aβ) and rescue a C. elegans model of Alzheimer’s disease. We found that these metabolites act by triggering a cytosolic unfolded protein response through the transcription factor HSF-1 and downstream chaperones HSP40/J-proteins DNJ-12 and DNJ-19. These results help rationalise previous observations regarding the possible anti-ageing benefits of these metabolites by providing a mechanism for their action. Taken together, our findings provide a link between metabolite homeostasis and protein homeostasis, which could inspire preventative interventions against neurodegenerative disorders.

scholarly journals Crosstalk between Different DNA Repair Pathways Contributes to Neurodegenerative Diseases

Biology ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 163
Author(s):  
Swapnil Gupta ◽  
Panpan You ◽  
Tanima SenGupta ◽  
Hilde Nilsen ◽  
Kulbhushan Sharma
Keyword(s):  
Dna Repair ◽  
Neurodegenerative Diseases ◽  
3D Models ◽  
Model Systems ◽  
Spinocerebellar Ataxias ◽  
C Elegans ◽  
Cellular Processes ◽  
Age Related ◽  
Damage Response ◽  
Lateral Sclerosis

Genomic integrity is maintained by DNA repair and the DNA damage response (DDR). Defects in certain DNA repair genes give rise to many rare progressive neurodegenerative diseases (NDDs), such as ocular motor ataxia, Huntington disease (HD), and spinocerebellar ataxias (SCA). Dysregulation or dysfunction of DDR is also proposed to contribute to more common NDDs, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we present mechanisms that link DDR with neurodegeneration in rare NDDs caused by defects in the DDR and discuss the relevance for more common age-related neurodegenerative diseases. Moreover, we highlight recent insight into the crosstalk between the DDR and other cellular processes known to be disturbed during NDDs. We compare the strengths and limitations of established model systems to model human NDDs, ranging from C. elegans and mouse models towards advanced stem cell-based 3D models.

scholarly journals Steroid hormones sulfatase inactivation extends lifespan and ameliorates age-related diseases

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mercedes M. Pérez-Jiménez ◽  
José M. Monje-Moreno ◽  
Ana María Brokate-Llanos ◽  
Mónica Venegas-Calerón ◽  
Alicia Sánchez-García ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Caenorhabditis Elegans ◽  
Protein Aggregation ◽  
Steroid Hormones ◽  
Sensory Neurons ◽  
Environmental Cues ◽  
Steroid Sulfatase ◽  
Loss Of Function ◽  
C Elegans ◽  
Age Related

AbstractAging and fertility are two interconnected processes. From invertebrates to mammals, absence of the germline increases longevity. Here we show that loss of function of sul-2, the Caenorhabditis elegans steroid sulfatase (STS), raises the pool of sulfated steroid hormones, increases longevity and ameliorates protein aggregation diseases. This increased longevity requires factors involved in germline-mediated longevity (daf-16, daf-12, kri-1, tcer-1 and daf-36 genes) although sul-2 mutations do not affect fertility. Interestingly, sul-2 is only expressed in sensory neurons, suggesting a regulation of sulfated hormones state by environmental cues. Treatment with the specific STS inhibitor STX64, as well as with testosterone-derived sulfated hormones reproduces the longevity phenotype of sul-2 mutants. Remarkably, those treatments ameliorate protein aggregation diseases in C. elegans, and STX64 also Alzheimer’s disease in a mammalian model. These results open the possibility of reallocating steroid sulfatase inhibitors or derivates for the treatment of aging and aging related diseases.

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