Ken Raj
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View article: Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice
Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice Open
Mice bred in 2021 were tested by the Interventions Testing Program (ITP) for possible lifespan benefits of 2BAct (2BA), dichloroacetate (DCA), Epicatechin (EPI), Forskolin (FSK), Halofuginone (HAL) and Mitoglitazone (MIT). All agents were …
View article: Disagreement on foundational principles of biological aging
Disagreement on foundational principles of biological aging Open
To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational is…
View article: Epigenetic predictors of species maximum life span and other life-history traits in mammals
Epigenetic predictors of species maximum life span and other life-history traits in mammals Open
By analyzing 15,000 samples from 348 mammalian species, we derive DNA methylation (DNAm) predictors of maximum life span ( R = 0.89), gestation time ( R = 0.96), and age at sexual maturity ( R = 0.85). Our maximum life-span predictor indic…
View article: DNA methylation GrimAge strongly predicts lifespan and healthspan
DNA methylation GrimAge strongly predicts lifespan and healthspan Open
It was unknown whether plasma protein levels can be estimated based on DNA methylation (DNAm) levels, and if so, how the resulting surrogates can be consolidated into a powerful predictor of lifespan. We present here, seven DNAm-based esti…
View article: DNA methylation-based estimator of telomere length
DNA methylation-based estimator of telomere length Open
Telomere length (TL) is associated with several aging-related diseases. Here, we present a DNA methylation estimator of TL (DNAmTL) based on 140 CpGs. Leukocyte DNAmTL is applicable across the entire age spectrum and is more strongly assoc…
View article: Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies
Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies Open
DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, w…
View article: Epigenetic predictors of species maximum lifespan and other life history traits in mammals
Epigenetic predictors of species maximum lifespan and other life history traits in mammals Open
Maximum lifespan is an intrinsic characteristic of a biological species and is defined as the longest time an individual of a species has been reported to survive. By analyzing 15K samples derived from 348 mammalian species representing 25…
View article: Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction
Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction Open
Young blood plasma is known to confer beneficial effects on various organs in mice and rats. However, it was not known whether plasma from young pigs rejuvenates old rat tissues at the epigenetic level; whether it alters the epigenetic clo…
View article: Post-exposure persistence of nitric oxide upregulation in skin cells irradiated by UV-A
Post-exposure persistence of nitric oxide upregulation in skin cells irradiated by UV-A Open
Evidence suggests that exposure to UV-A radiation can liberate nitric oxide from skin cells eliciting vasodilation in-vivo. However, the duration of nitric oxide release in skin cells after UV exposure is not well studied, with emphasis on…
View article: DNA methylation clocks for dogs and humans
DNA methylation clocks for dogs and humans Open
Significance Epigenetic estimators of age (known as clocks) allow one to identify interventions that slow or reverse aging. Previous epigenetic clocks only applied to one species at a time. Here, we describe epigenetic clocks that apply to…
View article: The relationship between epigenetic age and the hallmarks of aging in human cells
The relationship between epigenetic age and the hallmarks of aging in human cells Open
Epigenetic clocks are mathematically derived age estimators that are based on combinations of methylation values that change with age at specific CpGs in the genome. These clocks are widely used to measure the age of tissues and cells 1,2 …
View article: Isolation of five different primary cell types from a single sample of human skin
Isolation of five different primary cell types from a single sample of human skin Open
We have developed a technique to isolate primary keratinocytes, melanocytes, fibroblasts, preadipocytes, and microvascular endothelial cells from an individual sample of human skin. The protocol describes step-by-step instructions for proc…
View article: Post-exposure Persistence of Nitric Oxide Upregulation in Skin Cells Irradiated by UV-A 1
Post-exposure Persistence of Nitric Oxide Upregulation in Skin Cells Irradiated by UV-A 1 Open
Evidence suggests that exposure to the UV-A radiation can liberate nitric oxide from skin cells eliciting vasodilation in-vivo. However, the duration of nitric oxide release in skin cells after UV exposure is not well studied, with emphasi…
View article: Divergent age-related methylation patterns in long and short-lived mammals
Divergent age-related methylation patterns in long and short-lived mammals Open
Age-related changes to cytosine methylation have been extensively characterized across the mammalian family. Some cytosines that are conserved across mammals exhibit age-related methylation changes that are so consistent that they were use…
View article: DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders
DNA methylation clocks tick in naked mole rats but queens age more slowly than nonbreeders Open
Naked mole rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity and are resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging according to …
View article: Universal DNA Methylation Age Across Mammalian Tissues
Universal DNA Methylation Age Across Mammalian Tissues Open
Aging is often perceived as a degenerative process caused by random accrual of cellular damage over time. In spite of this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of th…
View article: Epigenetic clock and methylation studies in gray short-tailed opossums
Epigenetic clock and methylation studies in gray short-tailed opossums Open
The opossum ( Monodelphis domestica ), with its sequenced genome, ease of laboratory care and experimental manipulation, and unique biology, is the most used laboratory marsupial. Using the mammalian methylation array, we generated DNA met…
View article: Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity
Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity Open
DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age, epigenetic clocks, for many species. Using a custom methylation array, we generated DNA methylation data from n = 238 porcine tissues includ…
View article: Epigenetic clock and methylation studies in the rhesus macaque
Epigenetic clock and methylation studies in the rhesus macaque Open
Methylation levels at specific CpG positions in the genome have been used to develop accurate estimators of chronological age in humans, mice, and other species. Although epigenetic clocks are generally species-specific, the principles und…
View article: Epigenetic clock and methylation studies in cats
Epigenetic clock and methylation studies in cats Open
Human DNA methylation profiles have been used successfully to develop highly accurate biomarkers of aging (“epigenetic clocks”). Although these human epigenetic clocks are not immediately applicable to all species of the animal kingdom, th…
View article: Epigenetic clock and methylation studies in elephants
Epigenetic clock and methylation studies in elephants Open
Age‐associated DNA‐methylation profiles have been used successfully to develop highly accurate biomarkers of age ("epigenetic clocks") in humans, mice, dogs, and other species. Here we present epigenetic clocks for African and Asian elepha…
View article: Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging
Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging Open
Cattle are an attractive animal model of fertility in women due to their high degree of similarity relative to follicle selection, embryo cleavage, blastocyst formation, and gestation length. To facilitate future studies of the epigenetic …
View article: Epigenetic clock and methylation studies in dogs
Epigenetic clock and methylation studies in dogs Open
DNA methylation profiles have been used to develop biomarkers of aging known as epigenetic clocks, which predict chronological age with remarkable accuracy and show promise for inferring health status as an indicator of biological age. Epi…
View article: DNA Methylation Networks Underlying Mammalian Traits
DNA Methylation Networks Underlying Mammalian Traits Open
Summary Epigenetics has hitherto been studied and understood largely at the level of individual organisms. Here, we report a multi-faceted investigation of DNA methylation across 11,117 samples from 176 different species. We performed an u…
View article: DNA methylation clocks show slower progression of aging in naked mole-rat queens
DNA methylation clocks show slower progression of aging in naked mole-rat queens Open
Naked mole-rats (NMRs) live an exceptionally long life, appear not to exhibit age-related decline in physiological capacity, and are seemingly resistant to age-related diseases. However, it has been unknown whether NMRs also evade aging ac…