243 replies to this topic

[VP.]

If they won't publish results from their research I can't consider using them. It's too bad because it looks promising. They don't answer my messages so that's not a good sign. 

[QuestforLife]

If they won't publish results from their research I can't consider using them. It's too bad because it looks promising. They don't answer my messages so that's not a good sign. 

 

If you go on their website and click on the chat icon you can talk in real time with a knowledgeable member of the team, which is what I did. They may have published, I don't know - but even if they haven't, it's no different to MyDNAge, who use propriety methylation sites.

[albedo]

If you go on their website and click on the chat icon you can talk in real time with a knowledgeable member of the team, which is what I did. They may have published, I don't know - but even if they haven't, it's no different to MyDNAge, who use propriety methylation sites.

Yes, that could be a good approach. I also did a small search on co-founders such as Dr. Stubbs and Dr. Reik and found this work, a bit dated though (2017), which I will read: https://genomebiolog...017-1203-5#Sec8

[VP.]

If you go on their website and click on the chat icon you can talk in real time with a knowledgeable member of the team, which is what I did. They may have published, I don't know - but even if they haven't, it's no different to MyDNAge, who use propriety methylation sites.

I had a chat with Toby from Chronomics about what test they used for biological age. I asked if the used the older Horvath test or pehaps the new GrimAge test and this was his answer:

 

We build our own more accurate predictor of biological age, drawing on genome wide sequencing data rather than methyl arrays

 

 

I did not get an answer whether their test is published yet or  if it has been submitted. 

[VP.]

I had a chat with Toby from Chronomics about what test they used for biological age. I asked if the used the older Horvath test or pehaps the new GrimAge test and this was his answer:

 

 

 

I did not get an answer whether their test is published yet or  if it has been submitted. 

I talked some more to Toby and he said papers have been submitted on their research. 

[albedo]

https://gero.ai/bioage

(did not use it yet)

[albedo]

The following is a highly recommended review paper by Claudio Franceschi, an extremely prolific author on aging, creator of the "inflammaging" theory of aging and leader of many studies, also large ones funded by EU as NU-AGE, particularly on the models represented by centenarians where more recently he and his team focused on the gut microbiome.

 

The paper touches many of the topics investigated in this Forum and aging theories. The link to this particular thread being the digression on biological age and relative biomarkers, in particular: DNA metylation, N-glycans and gut microbiota profiling.

 

Franceschi C, Garagnani P, Morsiani C, et al. The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front Med (Lausanne). 2018;5:61.

 

"Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age to identify subjects at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers."

[VP.]

Strait from Steve Horvath: 

Rapamycin retards epigenetic ageing of keratinocytes independently of its effects on replicative senescence, proliferation and differentiation

 

The advent of epigenetic clocks has prompted questions about the place of epigenetic ageing within the current understanding of ageing biology. It was hitherto unclear whether epigenetic ageing represents a distinct mode of ageing or a manifestation of a known characteristic of ageing. We report here that epigenetic ageing is not affected by replicative senescence, telomere length, somatic cell differentiation, cellular proliferation rate or frequency. It is instead retarded by rapamycin, the potent inhibitor of the mTOR complex which governs many pathways relating to cellular metabolism. Rapamycin, however, is also an effective inhibitor of cellular senescence. Hence cellular metabolism underlies two independent arms of ageing – cellular senescence and epigenetic ageing. The demonstration that a compound that targets metabolism can slow epigenetic ageing provides a long-awaited point-of-entry into elucidating the molecular pathways that underpin the latter. Lastly, we report here an in vitro assay, validated in humans, that recapitulates human epigenetic ageing that can be used to investigate and identify potential interventions that can inhibit or retard it.

In summary, the observations above represent the first biological connection between epigenetic ageing and rapamycin. These results for human cells add to the evidence that extension of life, at least by rapamycin, is indeed accompanied by retardation of ageing. These observations also suggest that the life-extending property of rapamycin may be a resultant of its multiple actions which include, but not necessarily limited to suppression of cellular senescence [36–38,48] and epigenetic aging, with the possibility of augmentation of cellular proliferative potential.

 

https://www.aging-us...cle/101976/text

[albedo]

Insightful recent review paper also comparing blood and brain based biological age determination methodologies:

 

Gialluisi A, Di castelnuovo A, Donati MB, De gaetano G, Iacoviello L. Machine Learning Approaches for the Estimation of Biological Aging: The Road Ahead for Population Studies. Front Med (Lausanne). 2019;6:146.

[albedo]

Anther offering in case your have overlooked it. This is from the Elizabeth Parrish, CEO, company:

https://bioviva-scie...eal-my-dna-age/

[albedo]

A nice and recent review paper:

Zhavoronkov A, Li R, Ma C, Mamoshina P. Deep biomarkers of aging and longevity: from research to applications. Aging (Albany NY). 2019;11

 

[albedo]

In an interesting thread related to Heat Shock Protein, iPSC and epigenetic reprogramming, HighDesertWizard provided some of the results of several LongeCity Members participating to the Longecity biological age program using different methodologies:

 

https://www.longecit...ndpost&p=861944

 

Likely, many of those participants have large experience with interventions and equally likely keep a record of the relevant clinical biomarkers upon which is based the new Levine’s and Horvath’s clock recently published (An epigenetic biomarker of aging for lifespan and healthspan ) potentially tracking biological age. It would be interesting if they could compare with the Phenotypic Age as calculated by JGC and independently confirmed by myself here :

 

https://forum.rescue...-phenotypic-age

https://www.dropbox....ge_gen.xls?dl=0

 

Following the Phenotype Age determination (and Mortality Risk), Levine et al. also regressed the Phenotype Age on blood DNA methylation data of a particularly well characterized cohort (InCHIANTI), determining a new precise epigenetic biomarkers of aging, aka DNAm PhenoAge. The spreadsheet I reported in the above links allows a calculation of the Phenotype Age and just a rough estimation of the DNAm PhenoAge by fitting the regression data directly from the plot (see the JGC’s post for details) given in the Levine’s presentation:

 

Levine 2018 DNAm PhenoAge.PNG

http://gero.usc.edu/...AA/1.Levine.pdf

 

Anecdotally my data are:

 

Age: 63 years

Phenotypic Age: 46.1 years

Mortality Risk (10 years): 0.033

DNAm PhenoAge (rough estimate): 45.6 years

 

Something which is still unclear is the relative biological role the several clinically relevant biomarkers play in the determination of the Phenotype Age as discussed in the RescueElders Forum thread, e.g. the high weight of RDW and MCV when compared to inflammatory markers such as hr-CRP. You might wish to read the discussion also on that Forum. I am trying to better understand this point.

 

Interestingly, my data are extremely similar to what obtained using Aging.ai (V1.0 only) and also a ML/AI trained system on face images. Where the methodologies seem diverging is in the time trends of “biological age” so calculated which I am still understanding, the trends being more important than the absolute values when we want to track interventions, IMHO. But this will be for another post….

 

(edit: spelling)

 

The relative important weight of RDW in Levine's Phenotypic Age (see red in my quote) might be not so mysterious after all:

 

"...Variability in red blood cell (RBC) volumes (RBC distribution width: RDW) increases with age and is a strong predictor of mortality, incident CAD and cancer. In a study of 116,666 UK Biobank volunteers, genetic variants explained 29% of RDW individuals aged over 60 years and 33.8% of RDW in those aged < 50 years [222]. RDW was associated with 194 independent genetic signals (119 intronic), 71 implicated in autoimmune disease, body mass index, Alzheimer’s disease, longevity, age at menopause, bone density, myostasis, Parkinson’s disease and age-related macular degeneration. Pathway analysis showed enrichment for telomere maintenance, ribosomal RNA and apoptosis..."

 

Morris BJ, Willcox BJ, Donlon TA. Genetic and epigenetic regulation of human aging and longevity. Biochim Biophys Acta Mol Basis Dis. 2019;1865(7):1718-1744.

Edited by albedo, 05 December 2019 - 10:36 AM.

[ilanso]

I am looking for a consumer targeted bio-age offering that does not require you to fill in your chrono-age (ca). The idea is to keep them honest and prevent post-hoc corrections.

Ideally, their formula would involve several epigenetic markers in addition to the ca and they would send me a simplified one involving just one combined epi-factor (em) and my ca (eg epi-age=em*ca, where em is a personal constant based on my kit). I would then be able to compute my own epi-age and not worry it was retrofitted.

If, in the absence of such anonymous policy, I decided to give them a fake age and got back just one number (my fake epi-age), I would not be able to derive my real one. So a formula is definitely required, unless their original formula is independent of ca. 

[aribadabar]

I decided to give them a fake age and got back just one number (my fake epi-age), I would not be able to derive my real one. So a formula is definitely required, unless their original formula is independent of ca. 

 

Two questions:

 

1. How much off is your reported fake age from the real one? 5, 10, 20 years?

2. How the the result compare to your real chronological age?

 

Thanks!

[ilanso]

I said "If I decided" - haven't signed up with any of these firms before I can be assured they don't need my chrono age first.

 

I looked at their formula (for ages above 20):

DNAmAge=inverse.F(b0+b1CpG1+ . . . +b391CpG391)

 

Inverse.F(x)=21x+20

 

so

 

DNAmAge= 21*(b0+b1CpG1+ . . . +b391CpG391)+20

 

where the b0, b1, etc coefficient values are their proprietary ones, and the CpG values are read from your DNA.

 

Because the formula does not depend on your chronological age, this implies they could derive the bio-age directly from your DNA (provided you are older than 20), which is ideal. I have a nagging feeling. though, that b0, b1, etc are not just universal constants, but also derived from your chrono age.  

[Iporuru]

Patterns of Aging Biomarkers, Mortality, and Damaging Mutations Illuminate the Beginning of Aging and Causes of Early-Life Mortality

 

Highlights

• Mortality from age-related diseases is U-shaped with the nadir below reproductive age
• Quantitative biomarkers of aging change continuously throughout life
• Mutation burden causes early-life mortality and contributes to selection
• Aging is best defined by damage rather than mortality and starts very early in life

Summary

An increase in the probability of death has been a defining feature of aging, yet human perinatal mortality starts high and decreases with age. Previous evolutionary models suggested that organismal aging begins after the onset of reproduction. However, we find that mortality and incidence of diseases associated with aging follow a U-shaped curve with the minimum before puberty, whereas quantitative biomarkers of aging, including somatic mutations and DNA methylation, do not, revealing that aging starts early but is masked by early-life mortality. Moreover, our genetic analyses point to the contribution of damaging mutations to early mortality. We propose that mortality patterns are governed, in part, by negative selection against damaging mutations in early life, manifesting after the corresponding genes are first expressed. Deconvolution of mortality patterns suggests that deleterious changes rather than mortality are the defining characteristic of aging and that aging begins in very early life.

 

[albedo]

David Sinclair and team put up in BioRxv a paper where he looks at methionine restriction which looks effective, in mice, on a frailty index (FI) as measured by two different clocks in mice: "... FRIGHT (Frailty Inferred Geriatric Health Timeline) clock, a strong predictor of chronological age. A second model was trained on remaining lifespan to generate the AFRAID (Analysis of Frailty and Death) clock, which accurately predicts life expectancy and the efficacy of a lifespan extending intervention up to a year in advance..."

FIs' are well known indexed and capture many aspect of aging (we discussed these in this thread too, e.g. see here by Michael). I guess a good entry is the work by Rockwood & Mitnitski, look for them and FI.

I am interested to these and blood based biomarkers, look also at the recent "proteome clock" in humans by the Wyss-Coray's team at Stanford.

 

Age and life expectancy clocks based on machine learning analysis of mouse frailty

https://doi.org/10.1...19.12.20.884452

 

[albedo]

I am looking for a consumer targeted bio-age offering that does not require you to fill in your chrono-age (ca). The idea is to keep them honest and prevent post-hoc corrections.

Ideally, their formula would involve several epigenetic markers in addition to the ca and they would send me a simplified one involving just one combined epi-factor (em) and my ca (eg epi-age=em*ca, where em is a personal constant based on my kit). I would then be able to compute my own epi-age and not worry it was retrofitted.

If, in the absence of such anonymous policy, I decided to give them a fake age and got back just one number (my fake epi-age), I would not be able to derive my real one. So a formula is definitely required, unless their original formula is independent of ca. 

Indirectly, you rise an important point whether or not CA should be included in a BA estimation. W/o entering into the epigenetic discussion (but the point might be valid as well) I think jury is still not out on this and it is a controversial point. That I recollect, some as Klemera-Doubal argue I guess in favor of inclusion while others as Mitnitski and others argue against. You might refer to a couple of interesting readings:

Klemera P, Doubal S. A new approach to the concept and computation of biological age. Mech Ageing Dev. 2006;127(3):240-8.

Mitnitski A, Howlett SE, Rockwood K. Heterogeneity of Human Aging and Its Assessment. J Gerontol A Biol Sci Med Sci. 2017;72(7):877-884.

[albedo]

Anybody using this test? Comments?

https://www.elysiumh...com/en-us/index

[Iporuru]

Human Skin, Oral, and Gut Microbiomes Predict Chronological Age

Abstract

Human gut microbiomes are known to change with age, yet the relative value of human microbiomes across the body as predictors of age, and prediction robustness across populations is unknown. In this study, we tested the ability of the oral, gut, and skin (hand and forehead) microbiomes to predict age in adults using random forest regression on data combined from multiple publicly available studies, evaluating the models in each cohort individually. Intriguingly, the skin microbiome provides the best prediction of age (mean ± standard deviation, 3.8 ± 0.45 years, versus 4.5 ± 0.14 years for the oral microbiome and 11.5 ± 0.12 years for the gut microbiome). This also agrees with forensic studies showing that the skin microbiome predicts postmortem interval better than microbiomes from other body sites. Age prediction models constructed from the hand microbiome generalized to the forehead and vice versa, across cohorts, and results from the gut microbiome generalized across multiple cohorts (United States, United Kingdom, and China). Interestingly, taxa enriched in young individuals (18 to 30 years) tend to be more abundant and more prevalent than taxa enriched in elderly individuals (>60 yrs), suggesting a model in which physiological aging occurs concomitantly with the loss of key taxa over a lifetime, enabling potential microbiome-targeted therapeutic strategies to prevent aging.

[albedo]

Human Skin, Oral, and Gut Microbiomes Predict Chronological Age

.....

 

The link does not seem to open...

[Iporuru]

The link does not seem to open...

 

Here it is: https://msystems.asm...t/5/1/e00630-19
 

[albedo]

Little surprise ... David Sinclair soon commercializing a Horvath's epigenetic clock for $5-10 ?! Complement with what he is doing with InsideTracker tests based on blood? Interesting! Adding to his long list of companies and collaborations. See/listen at min 34:35 on here:

[Joe Garma]

That was great; thanks for posting.

 

I follow nearly everything that Sinclair puts out there (and have written much about his work), but this interview escaped my notice.

 

Note: You can get a very good approximation of your biological age via the Horvath technique with just a few blood test metrics. What he and a few other scientists did was to:

• USse an elaborate DNA analysis of many blood samples to find what they call the DNAm PhenoAge, a measure of the degree of DNA methylation present, a phenomenon associated with aging.
• Correlate this measure with the Phenotypic Age, showing that they track very well.

I wrote about it here: https://www.garmaonh...ur-bioage-test/ and if you type in your email address, you'll get a link to the Google Sheet to input your own numbers and get your bioage.

[albedo]

...

Note: You can get a very good approximation of your biological age via the Horvath technique with just a few blood test metrics.

...

 

You might also refer to previous posts in this thread and additionally also here:

https://forum.age-re...-phenotypic-age
 

[QuestforLife]

 

Note: You can get a very good approximation of your biological age via the Horvath technique with just a few blood test metrics.

 

The correlation between phenotypic age and chronological age is only ~0.65 (for a Caucasian - not significantly different with other ethnicity).

 

https://www.ncbi.nlm...les/PMC5940111/

 

See Supplement 1, aging-10-101414-s001.pdf

Figure 5b

 

Whereas the direct Horvath methylation test correlates 0.98 with chronological age. 

[albedo]

I was just waiting for this to happen. Here is in my view a quite pioneering work on biological age determination using ML/AI on microbiota. The study is still at level or preprint as per today:

 

"...Our most accurate DNN regressor achieved the MAE of 3.94 years. This performance is comparable with the 1.9 MAE of the PhotoAgeClock, 2.7 of the state of art methylation aging clock, 7.8 MAE transcriptomic aging clock and 5.5 MAE of the hematological aging clock published previously. We also developed a method for microbiological feature selection and annotation..."

 

Quite fascinating is that: "...Interestingly, while it contains both beneficial (e.g. Bifidobacterium) and pathogenic (e.g. Pseudomonas aeruginosa) microbes, seno-positive or seno-negative status is not determined by the nature of host-microbe interactions (Figure 12)..."

 

Human microbiome aging clocks based on deep learning and tandem of permutation feature importance and accumulated local effects

Fedor Galkin, Alexander Aliper, Evgeny Putin, Igor Kuznetsov, Vadim N Gladyshev, Alex Zhavoronkov

bioRxiv 507780; doi: https://doi.org/10.1101/507780

 

The paper is (finally) published:

Galkin F, Mamoshina P, Aliper A, et al. Human Gut Microbiome Aging Clock Based on Taxonomic Profiling and Deep Learning. iScience. 2020;23(6):101199.

https://www.cell.com...0042(20)30384-9

 Gut mb clock.PNG   202.44KB   0 downloads

"The human gut microbiome is a complex ecosystem that both affects and is
affected by its host status. Previous metagenomic analyses of gut microflora revealed
associations between specific microbes and host age. Nonetheless there
was no reliable way to tell a host’s age based on the gut community composition.
Here we developed a method of predicting hosts’ age based on microflora taxonomic
profiles using a cross-study dataset and deep learning. Our best model has
an architecture of a deep neural network that achieves the mean absolute error of
5.91 years when tested on external data. We further advance a procedure for
inferring the role of particular microbes during human aging and defining them
as potential aging biomarkers. The described intestinal clock represents a unique
quantitativemodel of gutmicroflora aging and provides a starting point for building
host aging and gut community succession into a single narrative."

 

(edit: add summary)
 

Edited by albedo, 15 June 2020 - 02:27 PM.

[albedo]

Viome launches world’s first at-home service to measure and improve immunity, inflammation, gut health and aging

https://www.globenew...-and-aging.html

Looks quite comprehensive. The test is based on a technology described in a paper not yet published though (on BioRxiv). Interesting ..

[albedo]

The urgency to test biomarkers of aging against human interventions. Hopefully with the TAME trial?

 DNAm.PNG   209.46KB   0 downloads

https://elifescience.../articles/58592

 

 

 

 

 

 

 

 

[Matt]

I've used http://aging.ai/ v3 and https://bioagecalc.azurewebsites.net/ to check out my biological age.

 

I'm 35-years-old (36 in October).

 

Aging.ai put me at 23-years-old (this is as low as it can predict as the data is cut off at 23).

 

AgelessR puts me at phenotypic age of 14.94 to 22.94 years-old.

 

Unfortunately, they don't test RDW here in the UK as standard practice, but as long as I put it within the normal range, it comes out somewhere between that range.

 

People keep saying I should get a DNA Methylation test, so I'm looking at that after I get get my genome sequenced and a new round of blood tests.