243 replies to this topic

[albedo]

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. 

Got similar trend w/ aging.ai, it looks typical (I mean in my case and from other "biohackers" i read about) the nos. turn out lower and I wonder why. Wrt RDW, as RDW = SD-MCV / MCV  (SD-MCV is the standard deviation of the distribution of red cell volumes, MCV) I will ask my lab. Maybe the machine will also calculate the RDW % but is not reported, for some reason, to the clinician. I know a competing lab in my region reporting both RDW and MCV though, so it must be possible. I use values I got in US, in the normal range. However, e.g. Levine's clock I discussed previously in this thread is quite sensitive to that value. Have you tried Levine's Phenotypic Age calculator? Please let us know and ask also you lab, it is very interesting.... Thank you.

 

 

[albedo]

An interesting review by Reason on GlycanAge. Anyone here used it?

https://www.fightagi...ation-patterns/

[albedo]

Good development by the Insilico folks. Do you have insight on how "optimal" biomarkers ranges are predicted in their report?

 optimal.PNG   350.9KB   0 downloads

https://deeplongevity.com/

[albedo]

Deep Longevity publishes an epigenetic aging clock of unprecedented accuracy

https://www.eurekale...l-dlp120720.php

"DNA methylation aging clocks have become an invaluable tool in biogerontology research since their inception in 2013. Today, a variety of machine learning approaches have been tested for the purpose of predicting human age based on molecular-level features. Among these, deep learning, or neural networks, is an especially promising approach that has been used to construct accurate clocks using blood biochemistry, transcriptomics, and microbiomics data—feats unachieved by other algorithms. In this article, we explore how deep learning performs in a DNA methylation setting and compare it to the current industry standard—the 353 CpG clock published in 2013. The aging clock we are presenting (DeepMAge) is a neural network regressor trained on 4,930 blood DNA methylation profiles from 17 studies. Its absolute median error was 2.77 years in an independent verification set of 1,293 samples from 15 studies. DeepMAge shows biological relevance by assigning a higher predicted age to people with various health-related conditions, such as ovarian cancer, irritable bowel diseases, and multiple sclerosis."

[albedo]

You might be interested to the latest video of Dr Michael Lustgarten in case you have missed it:

https://michaellustg...sts-since-2009/

[albedo]

Very informative interview by Rhonda Patrick to Steve Horvath, much work the time!

https://www.foundmyf...tm_medium=email

[albedo]

Do you know if and where one can have the DNA GrimAge test for (epigenetic) biological age?

[albedo]

Kaeser, S.A., Lehallier, B., Thinggaard, M. et al. A neuronal blood marker is associated with mortality in old age. Nat Aging 1, 218–225 (2021). https://doi.org/10.1...587-021-00028-4

 

"Neurofilament light chain (NfL) has emerged as a promising blood biomarker for the progression of various neurological diseases. NfL is a structural protein of nerve cells, and elevated NfL levels in blood are thought to mirror damage to the nervous system. We find that plasma NfL levels increase in humans with age (n = 122; 21–107 years of age) and correlate with changes in other plasma proteins linked to neural pathways. In centenarians (n = 135), plasma NfL levels are associated with mortality equally or better than previously described multi-item scales of cognitive or physical functioning, and this observation was replicated in an independent cohort of nonagenarians (n = 180). Plasma NfL levels also increase in aging mice (n = 114; 2–30 months of age), and dietary restriction, a paradigm that extends lifespan in mice, attenuates the age-related increase in plasma NfL levels. These observations suggest a contribution of nervous system functional deterioration to late-life mortality."

https://www.nature.c...587-021-00028-4

[Michael Lustgarten]

Quantifying Biological Age: Blood Test #1 in 2021

[albedo]

Thank you Michael.

• Mainly in winter, increase of CRP (it is highly sensitive) might be due to sub-clinical infections I guess. When highly symptomatic CRP sky rockets. Note also the WBC increased in your winter test.
• Sometime I wonder about the correlation of dietary intake of cholesterol vs serum TC: is there a rationale in thinking that if you try to reduce the intake you might trigger the body to produce more which then you see in your labs? Your data seem to contradict this.
• In general, I think the Phenotypic Age gives a general view but you can hardly use it to modulate one of the biomarkers to get a better result in biological age, IMHO

[Michael Lustgarten]

 

Thank you Michael.

• Mainly in winter, increase of CRP (it is highly sensitive) might be due to sub-clinical infections I guess. When highly symptomatic CRP sky rockets. Note also the WBC increased in your winter test.
• Sometime I wonder about the correlation of dietary intake of cholesterol vs serum TC: is there a rationale in thinking that if you try to reduce the intake you might trigger the body to produce more which then you see in your labs? Your data seem to contradict this.
• In general, I think the Phenotypic Age gives a general view but you can hardly use it to modulate one of the biomarkers to get a better result in biological age, IMHO

 

 

In my data, I don't see a trend for increasing hs-CRP. In contrast, from June-August, it has been higher because I suffer from seasonal allergies (pollen, grass). My WBCs increased in Feb 2020 because of a respiratory infection, which doesn't occur every year.

 

My intake of dietary cholesterol is normally, relatively low (~100 mg/d). When considering that higher blood levels of TC, LDL, HDL are correlated with lower hs-CRP in my data, it makes sense (to me) to try to increase those lipoproteins, even if it's only by 10 - 20mg/dL, total. As long as my hs-CRP is as low as possible (0.2 in my data), I'm relatively happy.

 

Phenotypic Age is just 1 metric. I try to optimize literally everything on the standard chem panel + CBC in terms what's found in youth and is associated with maximally reduced all-cause mortality risk.

[albedo]

...

Phenotypic Age is just 1 metric. I try to optimize literally everything on the standard chem panel + CBC in terms what's found in youth and is associated with maximally reduced all-cause mortality risk.

 

I stand with you on this. By construct it includes age, which I do not like much, and can be considered fundamentally a risk of mortality and maybe a proxy to the approach of optimizing simultaneously to minimal mortality the set of 9 clinically relevant biomarkers (remember, the latter emerged by a stringent validation out of 42 in two different cohorts, if you recollect the original papers, here and here). Your approach extends to higher than the 9 biomarkers.

[albedo]

In case you missed the last video of Dr Michael Lustgarten:

 

https://www.longecit...ndpost&p=904876

 

[albedo]

In case you missed the last video of Dr Michael Lustgarten:

 

https://www.longecit...ndpost&p=904876

 

Something which Michael did not fail to note in his video is the overlap between several clinically relevant biomarkers in different BA estimators.

 

This makes me more confident these methodologies do hint at a real underlying health status of individuals which can conveniently be followed longitudinally in the clinic.

 

Moreover, even if the BA estimators might be measuring different things as some authors (e.g. Belskly) claim, also reflecting the lack of an consensus of a definition of BA, they do provide a convenient simple list of biomarkers to watch clinically, e.g. in Levine's Phenotypic Age (Albumin, Creatinine, Glucose, C-reactive protein, Lymphocyte percent, Mean (red) cell volume, Red cell distribution width, Alkaline phosphatase, White blood cell count) or in KDM (C-reactive protein, serum creatinine, glycated hemoglobin, systolic blood pressure, serum albumin, total cholesterol, cytomegalovirus optical density, serum alkaline phosphatase, forced expiratory volume, serum urea
nitrogen), these 10 biomarkers from the latter successively further restricted to 7 when more stringent statistical methodologies are applied (PCA), i.e. C-reactive protein, glycated hemoglobin, serum albumin, cytomegalovirus optical density, serum alkaline phosphatase, forced expiratory volume, and systolic blood pressure.

 

doi: 10.18632/aging.101414

doi:10.1093/gerona/gls233

doi: 10.1093/aje/kwx346

 

 

 

Edited by albedo, 28 March 2021 - 06:03 PM.

[albedo]

.....

 

Moreover, even if the BA estimators might be measuring different things as some authors (e.g. Belskly) claim, also reflecting the lack of an consensus of a definition of BA, they do provide a convenient simple list of biomarkers to watch clinically, e.g. in Levine's Phenotypic Age (Albumin, Creatinine, Glucose, C-reactive protein, Lymphocyte percent, Mean (red) cell volume, Red cell distribution width, Alkaline phosphatase, White blood cell count) or in KDM (C-reactive protein, serum creatinine, glycated hemoglobin, systolic blood pressure, serum albumin, total cholesterol, cytomegalovirus optical density, serum alkaline phosphatase, forced expiratory volume, serum urea nitrogen), these 10 biomarkers from the latter successively further restricted to 7 when more stringent statistical methodologies are applied (PCA), i.e. C-reactive protein, glycated hemoglobin, serum albumin, cytomegalovirus optical density, serum alkaline phosphatase, forced expiratory volume, and systolic blood pressure....

 

Another excellent and validated set of biomarkers, overlapping to those in my previous post and reasonably simple to test longitudinally:

 

 PoA.PNG   360.96KB   0 downloads

 

Elliott, M.L., Caspi, A., Houts, R.M. et al. Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy. Nat Aging 1, 295–308 (2021). https://doi.org/10.1...587-021-00044-4

[Thingsvarious]

To me, Sinclair is the most overrated gerontologist there is.. Peter Attia talks about a patient of his having his DNA-methylation clock turned back 5 years by a 7 day fast. That is ridiculous. Methylation is no accurate way to measure biological age

[albedo]

Is there anyone here who has compared 1-1 aging.ai and young.ai for biological blood age?

[Michael Lustgarten]

I haven't, but at least one of the 3 versions of biological age quantification on aging.ai should be equivalent to young.ai.

[albedo]

I haven't, but at least one of the 3 versions of biological age quantification on aging.ai should be equivalent to young.ai.

 

It should isn't? But even if the number of biomarkers are the same I am not sure because of possible different methodologies? training data set? or whatever ... I am going to test one day just as a curiosity.
 

[QuestforLife]

Has anyone else seen this study?

 

The correlation between serum albumin concentration and aging is remarkable. If there was only one thing you could include in a biological aging clock, surely this would be it?
 
Estimating the survival advantage based on telomere length and serum biomarkers of aging
DOI: 10.1186/s12967-017-1267-8
 

The ALB concentration decreased with age and showed a good correlation with age, (R2 = 0.968, p < 0.001)

 

 

[Michael Lustgarten]

Has anyone else seen this study?

 

The correlation between serum albumin concentration and aging is remarkable. If there was only one thing you could include in a biological aging clock, surely this would be it?
 
Estimating the survival advantage based on telomere length and serum biomarkers of aging
DOI: 10.1186/s12967-017-1267-8
 

 

 

 

I cover how albumin changes during aging (in a study that included > 1 million subjects) and how higher levels are associated with reduced all-cause mortality risk starting at 6:36 in this video:

[albedo]

@QuestforLife and @Michael Lustgarten

 

Great finding to read, thank you. Your are right QuestforLife re the incredible correlation of albumin in Fig 1: "...ALB showed a good linear relationship with age, indicating an aging indicator..." I also found insightful the inflection points for TL, TC and TG in Fig 2: "...We found that the TC and TG had a reverse turning point in the elderly group [28], indicating that the two indicators showed survival advantage indicators similar to telomere length...". I guess it is always good to look at these biomarkers in a composite mode.

 

Yes, have seen your video @Michael. What I like most is your proactive dietary tracking approach looking at ACM and extracting correlations to guide you. Despite correlation is not causation and mechanistically we lack better understanding, it is maybe the best hint where to look isn't? Michael, you also touched elsewhere on other biomarkers emerging strong, e.g. RDW,  in Levine's Phenotypic Age and also Aging.Ai (or Young.Ai): using PFI (feature importance) techniques, RDW, albumin and few others always come up high in importance:

 

 Blood biomarkers PFI.PNG   71.71KB   0 downloads

(from the Insilico folks: https://medium.com/l...i-5bc989f6805e)

 

 

 

 

 

 

 

 

[QuestforLife]

Despite correlation is not causation and mechanistically we lack better understanding, it is maybe the best hint where to look isn't?

Agree correlations can tell us where to look, but it doesn't take a genius to figure out a likely mechanism by which beta carotene elevates serum albumin.

Beta carotene is an antioxidant.
Beta carotene binds to albumin (doi: 10.1016/j.foodchem.2015.01.133)
Oxidised albumin has a higher catabolic rate than the reduced form (https://doi.org/10.1016/0167-4838(94)90251-8).
Therefore beta carotene increases serum albumin concentration.

From this comes a testable prediction. Astaxanthin, a more powerful antioxidant than beta carotene, which also binds to albumin, will increase serum albumin level atleast as much as beta carotene.

[albedo]

...

From this comes a testable prediction. Astaxanthin, a more powerful antioxidant than beta carotene, which also binds to albumin, will increase serum albumin level atleast as much as beta carotene.

 

Impressive and good line of thought. Thank you. Who knows maybe my 6.5 mg average daily astaxanthin from my supplementation might also have an impact when adding to dietary intake which I do not track (bad me...) but pretend to be reasonable (incl. regular carrots). My serum beta carotene also tends to be higher than the ref. range. My albumin, while slowly declining since I track is pretty good at 48 g/l to my age (65+) i guess.

 

[Krell]

My February blood test shows albumin at 49 g/l at age 76, which the graph shows as average for a 10 year old!

 

Now I see why I score on the young side on biological age tests.

[aribadabar]

Has anyone else seen this study?

 

The correlation between serum albumin concentration and aging is remarkable. If there was only one thing you could include in a biological aging clock, surely this would be it?
 
Estimating the survival advantage based on telomere length and serum biomarkers of aging
DOI: 10.1186/s12967-017-1267-8
 

 

 

 

Is this relationship also causative so albumin IV drip, like NAD+ drip, would prove to be an anti-aging intervention?

[Michael Lustgarten]

I've been saying that albumin is likely the most underrated biomarker. See this video, which has more data for the albumin-longevity link:

https://youtu.be/Hvk1wvDmlms?t=394

[Phoebus]

Delivery of Recombinant Serum Albumin Extends Life Span in Old Mice

 

https://www.fightagi...an-in-old-mice/

 

So its looking like you don't need to infuse whole blood from young to old mice, or even plasma, to extend life span, you just need the albumin. This seems like a  no brainer for a human trial. Don't we already have some data on the safety of albumin transfusions? Why are we not doing a human trial on this? Seems simple, straightforward, and relatively safe. 

[Phoebus]

 

 

In multivariate analyses, serum albumin was associated significantly with muscle mass after age, protein intake, physical activity, and comorbidity were controlled for in men and women. This study suggests that decreases with age in serum albumin concentrations are associated with muscle loss (sarcopenia) in the elderly. This association is independent of other factors that may affect muscle mass and albumin concentration. We suggest that the increased risk of disability with low serum albumin concentrations observed in the elderly may actually reflect an association with sarcopenia.

https://academic.oup...0708?login=true

 

 

And this study here looked at Synthetic food preservatives like sodium acetate (SA), sodium benzoate (SB), potassium sorbate (PS) and Butyl paraben (BP) and how they bind to and interact with albumin. This could be a mechanism by which processed foods decrease life span. 

 

https://www.scienced...308814619307915

 

 

 

Sodium intake is positively related to urinary albumin excretion. This relation is more pronounced in subjects with a higher BMI. These results suggest that high sodium intake may unfavourably influences cardiovascular prognosis especially in overweight and obese subjects.

https://onlinelibrar...96.2004.01390.x

 

I wonder if "sodium intake" is heavily associated here with junk food and chips and fries? 

 

IN this study serum albumin is positively correlated with serum potassium levels. So sodium seems bad for albumin, potassium seems good 

 

https://www.ningen-d...15_Thesis_3.pdf

 

this study showed albumin levels were both a long term and short term predictor of mortality 

 

 

 

 The results show that the risk of mortality for subjects with albumin values of 40 g/liter and over was 0.46 of the risk for those with albumin values below 40 g/liter, after controlling for the confounders age, blood urea nitrogen, triglyceride, history of diseases, and inability to shop owing to medical conditions. Similarly, albumin was also inversely associated with mortality among institutionalized subjects even after controlling for the confounders age, sex, blood urea nitrogen, transferrin, and history of stroke. However, the association was no longer significant among the institutionalized population once the deaths that occurred within the first 3 years after study participation were eliminated. The results indicate that albumin is a long-term predictor of mortality among noninstitutionalized subjects and increased mortality is not only a result of age, history of chronic diseases, medication use, or protein intake. Among institutionalized subjects, albumin appeared to be a short-term predictor of mortality.

 

https://www.scienced...895435696001357

Edited by Phoebus, 15 April 2021 - 03:19 PM.

[Lady4T]

Very interesting about albumin...  The correlation is undeniable.

Is anyone considering injecting albumin?