Cellular senescence is believed to contribute to aging and disease through the activity of secreted factors that promote inflammation, remodel the extracellular matrix, and adversely modify the behavior of non-senescent cells. While the markers and properties of senescent cells are still under investigation, it is postulated that cellular senescence manifests in vivo as the consequence […]
Publications
Here lies all of this lab's publications by order of date. Click on the title of the paper to get more information about a publication, including the abstract, date of publication, and open access link if applicable.
Fail-tests of DNA methylation clocks, and development of a noise barometer for measuring epigenetic pressure of aging and disease
This study shows that Elastic Net (EN) DNA methylation (DNAme) clocks have low accuracy of predictions for individuals of the same age and a low resolution between healthy and disease cohorts; caveats inherent in applying linear model to non-linear processes. We found that change in methylation of cytosines with age is, interestingly, not the determinant […]
Old plasma dilution reduces human biological age: a clinical study.
This work extrapolates to humans the previous animal studies on blood heterochronicity and establishes a novel direct measurement of biological age. Our results support the hypothesis that, similar to mice, human aging is driven by age-imposed systemic molecular excess, the attenuation of which reverses biological age, defined in our work as a deregulation (noise) of […]
Small-animal blood exchange is an emerging approach for systemic aging research
We describe a small-animal blood exchange approach developed for aging research as an alternative to heterochronic parabiosis or plasma injections. In parabiosis, animals are surgically coupled, which has several disadvantages, including difficulty controlling experimental procedure, the effects of shared organs, environmental enrichment from jointly exploring the housing enclosure, involuntary exercise and an imprecise onset of […]
Mehdipour, M., Amiri, P., Liu, C. et al. Small-animal blood exchange is an emerging approach for systemic aging research. Nat Protoc (2022). https://doi.org/10.1038/s41596-022-00731-5
Systemic induction of senescence in young mice after single heterochronic blood exchange
Ageing is the largest risk factor for many chronic diseases. Studies of heterochronic parabiosis, substantiated by blood exchange and old plasma dilution, show that old-age-related factors are systemically propagated and have pro-geronic effects in young mice. However, the underlying mechanisms how bloodborne factors promote ageing remain largely unknown […]
Jeon, O.H., Mehdipour, M., Gil, TH. et al. Systemic induction of senescence in young mice after single heterochronic blood exchange. Nat Metab (2022). https://doi.org/10.1038/s42255-022-00609-6
Autologous treatment for ALS with implication for broad neuroprotection
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive loss of motor neurons (MNs), leading to paralysis, respiratory failure and death within 2–5 years of diagnosis. The exact mechanisms of sporadic ALS, which comprises 90% of all cases, remain unknown. In familial ALS, mutations in superoxide dismutase (SOD1) cause 10% of cases. The secretome of PSCs […]
Kim, D., Kim, S., Sung, A. et al. Autologous treatment for ALS with implication for broad neuroprotection. Transl Neurodegener 11, 16 (2022). https://doi.org/10.1186/s40035-022-00290-5
Mechanisms and Minimization of False Discovery of Metabolic Bioorthogonal Noncanonical Amino Acid Proteomics
Metabolic proteomics has been widely used to characterize dynamic protein networks in many areas of biomedicine, including in the arena of tissue aging and rejuvenation. Bioorthogonal noncanonical amino acid tagging (BONCAT) is based on mutant methionine-tRNA synthases (MetRS) that incorporates metabolic tags, for example, azidonorleucine [ANL], into newly synthesized proteins. BONCAT revolutionizes metabolic proteomics, because […]
Chao Liu, Nathan Wong, Etsuko Watanabe, William Hou, Leonardo Biral, Jonalyn DeCastro, Melod Mehdipour, Kiana Aran, Michael J. Conboy, and Irina M. Conboy.Mechanisms and Minimization of False Discovery of Metabolic Bioorthogonal Noncanonical Amino Acid Proteomics. Rejuvenation Research. Apr 2022.95-109.http://doi.org/10.1089/rej.2022.0019
Erythrocytes, a New Contributor to Age-Associated Loss of Blood–Brain Barrier Integrity
Blood exchanges between young and old partners demonstrate old blood has a detrimental effect on brain health of young animals. Previous studies primarily investigate soluble blood factors, such as transforming growth factor-beta, on the brain and the blood–brain barrier (BBB). However, the role of blood cellular components, particularly erythrocytes, has not been defined. Erythrocyte morphology […]
Amiri, P., DeCastro, J., Littig, J., Lu, H.-W., Liu, C., Conboy, I., Aran, K., Erythrocytes, a New Contributor to Age-Associated Loss of Blood–Brain Barrier Integrity. Adv. Sci. 2021, 8, 2101912. https://doi.org/10.1002/advs.202101912
Rapid and Electronic Identification and Quantification of Age-Specific Circulating Exosomes via Biologically Activated Graphene Transistors
Increasing access to modern clinical practices concomitantly extends lifespan, ironically revealing new classes of degenerative and inflammatory diseases of later years. Here, an electronic graphene field-effect transistor (gFET) is reported, termed EV-chip, for label-free, rapid identification and quantification of exosomes (EV) associated with aging through specific surface markers, CD63 and CD151. Studies suggest that blood-derived […]
Hajian, R., DeCastro, J., Parkinson, J., Kane, A., Camelo, A. F. R., Chou, P. P., Yang, J., Wong, N., Hernandez, E. D. O., Goldsmith, B., Conboy, I., Aran, K., Rapid and Electronic Identification and Quantification of Age-Specific Circulating Exosomes via Biologically Activated Graphene Transistors. Adv. Biology 2021, 5, 2000594. https://doi.org/10.1002/adbi.202000594
Discrimination of single-point mutations in unamplified genomic DNA via Cas9 immobilized on a graphene field-effect transistor
Simple and fast methods for the detection of target genes with single-nucleotide specificity could open up genetic research and diagnostics beyond laboratory settings. We recently reported a biosensor for the electronic detection of unamplified target genes using liquid-gated graphene field-effect transistors employing an RNA-guided catalytically deactivated CRISPR-associated protein 9 (Cas9) anchored to a graphene monolayer. […]
Balderston, S., Taulbee, J.J., Celaya, E. et al. Discrimination of single-point mutations in unamplified genomic DNA via Cas9 immobilized on a graphene field-effect transistor. Nat Biomed Eng 5, 713–725 (2021). https://doi.org/10.1038/s41551-021-00706-z