Epigenetic models developed for plains zebras predict age in domestic horses and endangered equids

AbstractEffective conservation and management of threatened wildlife populations require an accurate assessment of age structure to estimate demographic trends and population viability. Epigenetic aging models are promising developments because they estimate individual age with high accuracy, accurately predict age in related species, and do not require invasive sampling or intensive long-term studies. Using blood and biopsy samples from known age plains zebras (Equus quagga), we model epigenetic aging using two approaches: the epigenetic clock (EC) and the epigenetic pacemaker (EPM). The plains zebra EC has the potential for broad application within the genus Equus given that five of the seven extant wild species of the genus are threatened. We test the EC’s ability to predict age in sister taxa, including two endangered species and the more distantly related domestic horse, demonstrating high accuracy in all cases. By comparing chronological and estimated age in plains zebras, we investigate age acceleration as a proxy of health status. An interaction between chronological age and inbreeding is associated with age acceleration estimated by the EPM, suggesting a cumulative effect of inbreeding on biological aging throughout life.

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Epigenetic models predict age and aging in plains zebras and other equids

10.1101/2021.03.29.437607 ◽

2021 ◽

Author(s):

Brenda Larison ◽

Gabriela M. Pinho ◽

Amin Hagani ◽

Joseph A. Zoller ◽

Caesar Z. Li ◽

...

Keyword(s):

High Accuracy ◽

Epigenetic Aging ◽

Complex Pedigree ◽

Domestic Horses ◽

Wildlife Populations ◽

Conservation Concern ◽

Aging Models ◽

Methylation Patterns ◽

Genomic Methylation ◽

Effective Conservation

ABSTRACTFive of the seven extant wild species of the genus Equus are species of significant conservation concern. Effective conservation and management of such threatened wildlife populations depends on the ability to estimate demographic trends and population viability and therefore requires accurate assessment of age structure. However, reliably aging wildlife is challenging as many methods are highly invasive, inaccurate, or both. Epigenetic aging models, which estimate individual age with high accuracy based on genomic methylation patterns, are promising developments in this regard. Importantly, epigenetic aging models developed for one species can potentially predict age with high accuracy in sister taxa. Using blood and biopsy samples from known age plains zebras (Equus quagga), we developed epigenetic clocks (ECs) to predict chronological age, and epigenetic pacemaker (EPM) models to predict biological age. We tested the ability of our blood-based EC to predict ages of Grevy’s zebras, Somali asses and domestic horses, from blood samples. Because our samples came from a population with a complex pedigree, we also leveraged information from a previous sequencing effort to measure the association between levels of inbreeding (F and ROH) and the age acceleration as measured by DNA methylation. The resulting models describe the trajectory of epigenetic aging in plains zebras and accurately predict the ages of plains zebras and other equids. We found moderate support for a slight acceleration of aging with increased inbreeding.

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The costs of competition: high social status males experience accelerated epigenetic aging in wild baboons

10.1101/2020.02.22.961052 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jordan A. Anderson ◽

Rachel A. Johnston ◽

Amanda J. Lea ◽

Fernando A. Campos ◽

Tawni N. Voyles ◽

...

Keyword(s):

Dominance Rank ◽

Natural Populations ◽

Life History Strategy ◽

Male Dominance ◽

Biological Aging ◽

Epigenetic Clock ◽

Epigenetic Aging ◽

Epigenetic Age ◽

Aging Rates ◽

Young Life

AbstractAging, for virtually all life, is inescapable. However, within populations, biological aging rates vary. Understanding sources of variation in this process is central to understanding the biodemography of natural populations. We constructed a DNA methylation-based age predictor for an intensively studied wild baboon population in Kenya. Consistent with findings in humans, the resulting “epigenetic clock” closely tracks chronological age, but individuals are predicted to be somewhat older or younger than their known ages. Surprisingly, these deviations are not explained by the strongest predictors of lifespan in this population, early adversity and social integration. Instead, they are best predicted by male dominance rank: high-ranking males are predicted to be older than their true ages, and epigenetic age tracks changes in rank over time. Our results argue that achieving high rank for male baboons—the best predictor of reproductive success—imposes costs consistent with a “live fast, die young” life history strategy.

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Deconvolution of the epigenetic age discloses distinct inter-personal variability in epigenetic aging patterns

10.1101/2021.06.20.449142 ◽

2021 ◽

Author(s):

Tamar Shahal ◽

Elad Segev ◽

Thomas Konstantinovsky ◽

Yonit Marcus ◽

Gabi Shefer ◽

...

Keyword(s):

Healthy Subjects ◽

Interindividual Variability ◽

Chronological Age ◽

Biological Aging ◽

Epigenetic Clock ◽

Cpg Sites ◽

Epigenetic Aging ◽

Epigenetic Age ◽

Shed Light

Epigenetic age not only correlates with chronological age but predicts morbidity and mortality. We assumed that deconvolution of epigenetic age to its individual components could shed light on the diversity of epigenetic, and by inference, biological aging. Using the Horvath original epigenetic clock, we identified several CpG sites linked to distinct genes that quantitatively explain much of the interpersonal variability in epigenetic aging, with secretagogin and malin showing the most dominant effects. The analysis shows that the same epigenetic age for any given chronological age can be accounted for by variable contributions of identifiable CpG sites; that old epigenetic relative to chronological age is mostly explained by the same CpG sites, mapped to genes showing the highest interindividual variability differences in healthy subjects but not in subjects with type 2 diabetes. This paves the way to form personalized aging cards indicating the sources of accelerated/decelerated epigenetic aging in each examinee, en route to targeting specific sites as indicators, and perhaps treatment targets of personal undesirable age drifting.

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Effect of Long-Term Caloric Restriction on DNA Methylation Measures of Biological Aging in Healthy Adults: CALERIETM Trial Analysis

10.1101/2021.09.21.21263912 ◽

2021 ◽

Author(s):

reem waziry ◽

David L corcoran ◽

Kim M Huffman ◽

Michael S Kobor ◽

Meeraj Kothari ◽

...

Keyword(s):

Dna Methylation ◽

Controlled Trial ◽

Model Organisms ◽

Biological Aging ◽

Control Group ◽

Epigenetic Clock ◽

Long Term Effects ◽

Cohen’S D ◽

Cohen's D

Calorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological aging in humans using DNA methylation analysis of blood samples from N=197 participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIETM) randomized controlled trial. We quantified CR effects on biological aging by comparing change scores for six epigenetic-clock and Pace-of-Aging measures between n=128 CR-group and n=69 ad-libitum-control-group participants at 12- and 24-month follow-ups. CR effects were strongest for DunedinPACE Pace of Aging (12-month Cohen's d=0.3; 24-month Cohen's d=0.2, p<0.01 for both), followed by DunedinPoAm and the GrimAge epigenetic clock, although effects for these measures were not statistically different from zero (p>0.08). CR effects for other epigenetic clocks were in the opposite direction (all p>0.15). CALERIE intervention slowed Pace of Aging but showed minimal effect on epigenetic clocks hypothesized to reflect longer term accumulation of aging burden.

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Does the epigenetic clock GrimAge predict mortality independent of genetic influences: an 18 year follow-up study in older female twin pairs

Clinical Epigenetics ◽

10.1186/s13148-021-01112-7 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Föhr Tiina ◽

Waller Katja ◽

Viljanen Anne ◽

Sanchez Riikka ◽

Ollikainen Miina ◽

...

Keyword(s):

Mortality Risk ◽

Genetic Factors ◽

Strong Predictor ◽

Genetic Influences ◽

Biological Aging ◽

Epigenetic Clock ◽

Twin Design ◽

Epigenetic Aging ◽

Epigenetic Age

Abstract Background Epigenetic clocks are based on DNA methylation (DNAm). It has been suggested that these clocks are useable markers of biological aging and premature mortality. Because genetic factors explain variations in both epigenetic aging and mortality, this association could also be explained by shared genetic factors. We investigated the influence of genetic and lifestyle factors (smoking, alcohol consumption, physical activity, chronic diseases, body mass index) and education on the association of accelerated epigenetic aging with mortality using a longitudinal twin design. Utilizing a publicly available online tool, we calculated the epigenetic age using two epigenetic clocks, Horvath DNAmAge and DNAm GrimAge, in 413 Finnish twin sisters, aged 63–76 years, at the beginning of the 18-year mortality follow-up. Epigenetic age acceleration was calculated as the residuals from a linear regression model of epigenetic age estimated on chronological age (AAHorvath, AAGrimAge, respectively). Cox proportional hazard models were conducted for individuals and twin pairs. Results The results of the individual-based analyses showed an increased mortality hazard ratio (HR) of 1.31 (CI95: 1.13–1.53) per one standard deviation (SD) increase in AAGrimAge. The results indicated no significant associations of AAHorvath with mortality. Pairwise mortality analyses showed an HR of 1.50 (CI95: 1.02–2.20) per 1 SD increase in AAGrimAge. However, after adjusting for smoking, the HR attenuated substantially and was statistically non-significant (1.29; CI95: 0.84–1.99). Similarly, in multivariable adjusted models the HR (1.42–1.49) was non-significant. In AAHorvath, the non-significant HRs were lower among monozygotic pairs in comparison to dizygotic pairs, while in AAGrimAge there were no systematic differences by zygosity. Further, the pairwise analysis in quartiles showed that the increased within pair difference in AAGrimAge was associated with a higher all-cause mortality risk. Conclusions In conclusion, the findings suggest that DNAm GrimAge is a strong predictor of mortality independent of genetic influences. Smoking, which is known to alter DNAm levels and is built into the DNAm GrimAge algorithm, attenuated the association between epigenetic aging and mortality risk.

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High social status males experience accelerated epigenetic aging in wild baboons

eLife ◽

10.7554/elife.66128 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jordan A Anderson ◽

Rachel A Johnston ◽

Amanda J Lea ◽

Fernando A Campos ◽

Tawni N Voyles ◽

...

Keyword(s):

Dominance Rank ◽

Natural Populations ◽

Life History Strategy ◽

Male Dominance ◽

Biological Aging ◽

Epigenetic Clock ◽

Epigenetic Aging ◽

Epigenetic Age ◽

Aging Rates ◽

Young Life

Aging, for virtually all life, is inescapable. However, within populations, biological aging rates vary. Understanding sources of variation in this process is central to understanding the biodemography of natural populations. We constructed a DNA methylation-based age predictor for an intensively studied wild baboon population in Kenya. Consistent with findings in humans, the resulting 'epigenetic clock' closely tracks chronological age, but individuals are predicted to be somewhat older or younger than their known ages. Surprisingly, these deviations are not explained by the strongest predictors of lifespan in this population, early adversity and social integration. Instead, they are best predicted by male dominance rank: high-ranking males are predicted to be older than their true ages, and epigenetic age tracks changes in rank over time. Our results argue that achieving high rank for male baboons—the best predictor of reproductive success—imposes costs consistent with a 'live fast, die young' life history strategy.

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Leopard Density Estimation within an Enclosed Reserve, Namibia Using Spatially Explicit Capture-Recapture Models

Animals ◽

10.3390/ani9100724 ◽

2019 ◽

Vol 9 (10) ◽

pp. 724

Author(s):

Noack ◽

Heyns ◽

Rodenwoldt ◽

Edwards

Keyword(s):

Management Strategies ◽

Camera Traps ◽

Spatially Explicit ◽

Conservation Areas ◽

Term Survival ◽

New Class ◽

Capture Recapture ◽

Wildlife Populations ◽

Effective Conservation

The establishment of enclosed conservation areas are claimed to be the driving force for the long-term survival of wildlife populations. Whilst fencing provides an important tool in conservation, it simultaneously represents a controversial matter as it stops natural migration processes, which could ultimately lead to inbreeding, a decline in genetic diversity and local extinction if not managed correctly. Thus, wildlife residing in enclosed reserves requires effective conservation and management strategies, which are strongly reliant on robust population estimates. Here, we used camera traps combined with the relatively new class of spatially explicit capture-recaptured models (SECR) to produce the first reliable leopard population estimate for an enclosed reserve in Namibia. Leopard density was estimated at 14.51 leopards/100 km2, the highest recorded density in Namibia to date. A combination of high prey abundance, the absence of human persecution and a lack of top-down control are believed to be the main drivers of the recorded high leopard population. Our results add to the growing body of literature which suggests enclosed reserves have the potential to harbour high densities and highlight the importance of such reserves for the survival of threatened species in the future.

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High accuracy but low consistency in children’s long-term recall of a real-life stressful event

Journal of Experimental Child Psychology ◽

10.1016/j.jecp.2014.05.009 ◽

2014 ◽

Vol 126 ◽

pp. 357-368 ◽

Cited By ~ 7

Author(s):

Gunn Astrid Baugerud ◽

Svein Magnussen ◽

Annika Melinder

Keyword(s):

Real Life ◽

High Accuracy ◽

Stressful Event

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A New Monocyte Epigenetic Clock Reveals Effects of Alcohol Consumption on Epigenetic Aging in Three Independent Cohorts

10.1101/2021.03.22.436488 ◽

2021 ◽

Author(s):

Xiaoyu Liang ◽

Rajita Sinha ◽

Amy C. Justice ◽

Mardge H. Cohen ◽

Bradley E. Aouizerat ◽

...

Keyword(s):

Alcohol Consumption ◽

Hiv Infection ◽

Clinical Decision Making ◽

Clinical Decision ◽

Biological Age ◽

Biological Aging ◽

Epigenetic Clock ◽

Excessive Alcohol Consumption ◽

Epigenetic Age ◽

The Impact

AbstractBackgroundExcessive alcohol consumption increases the risk of aging-related comorbidities and mortality. Assessing the impact of alcohol consumption on biological age is important for clinical decision-making and prevention. Evidence shows that alcohol alters monocyte function, and age is associated with DNA methylome and transcriptomic changes among monocytes. However, no monocyte-based epigenetic clock is currently available. In this study, we developed a new monocyte-based DNA methylation clock (MonoDNAmAge) by using elastic net regularization. The MonoDNAmAge was validated by benchmarking using epigenetic age acceleration (EAA) in HIV infection. Using MonoDNAmAge clock as well as four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on biological aging in three independent cohorts (N=2,242).ResultsMonoDNAmAge, comprised of 186 CpG sites, was highly correlated with chronological age (rtraining=0.96, p<2.20E-16; rtesting=0.86, p=1.55E-141). The MonoDNAmAge clock predicted an approximately 10-year age acceleration from HIV infection in two cohorts. Quadratic regression analysis showed a nonlinear relationship between MonoDNAmAge and alcohol consumption in the Yale Stress Center Community Study (YSCCS, pmodel=4.55E-08, px2 =7.80E-08) and in the Veteran Aging Cohort Study (VACS, pmodel=1.85E-02, px2 =3.46E-02). MonoDNAmAge and light alcohol consumption showed a negative linear relationship in the Women’s Interagency HIV Study (WIHS, β=-2.63, px=2.82E-06). Heavy consumption increased EAAMonoDNAmAge up to 1.60 years in the VACS while light consumption decreased EAAMonoDNAmAge to 2.66 years in the WIHS. These results were corroborated by the four established epigenetic clocks.ConclusionsWe observed a nonlinear effect of alcohol consumption on epigenetic age that is estimated by a novel monocyte-based “clock” in three distinct cohorts, highlighting the complex effects of alcohol consumption on biological age.

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Further evidence of a cumulative effect of social disadvantage on risk of psychosis

Psychological Medicine ◽

10.1017/s0033291716002993 ◽

2016 ◽

Vol 47 (5) ◽

pp. 913-924 ◽

Cited By ~ 19

Author(s):

S. A. Stilo ◽

C. Gayer-Anderson ◽

S. Beards ◽

K. Hubbard ◽

A. Onyejiaka ◽

...

Keyword(s):

Local Population ◽

Control Sample ◽

Cumulative Effect ◽

Social Disadvantage ◽

Psychiatric Services ◽

Cumulative Effects ◽

First Episode ◽

Increased Risk ◽

First Contact

BackgroundA growing body of evidence suggests that indicators of social disadvantage are associated with an increased risk of psychosis. However, only a few studies have specifically looked at cumulative effects and long-term associations. The aims of this study are: To compare the prevalence of specific indicators of social disadvantage at, and prior to, first contact with psychiatric services in patients suffering their first episode of psychosis and in a control sample. To explore long-term associations, cumulative effects, and direction of effects.MethodWe collected information on social disadvantage from 332 patients and from 301 controls recruited from the local population in South London. Three indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analysed.ResultsAcross all the domains considered, cases were more likely to report social disadvantage than were controls. Compared with controls, cases were approximately two times more likely to have had a parent die and approximately three times more likely to have experienced a long-term separation from one parent before the age of 17 years. Cases were also more likely than controls to report two or more indicators of adult social disadvantage, not only at first contact with psychiatric services [odds ratio (OR) 9.5], but also at onset of psychosis (OR 8.5), 1 year pre-onset (OR 4.5), and 5 years pre-onset (OR 2.9).ConclusionsGreater numbers of indicators of current and long-term exposure are associated with progressively greater odds of psychosis. There is some evidence that social disadvantage tends to cluster and accumulate.

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