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Ron Put

Levine Phenotypic Age Spreadsheet

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Apologies if this has been posted before, my search didn't find anything. Below is the abstract from the paper summarizing certain identified biomarkers of aging.

An epigenetic biomarker of aging for lifespan and healthspan

"Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging." https://www.ncbi.nlm.nih.gov/pubmed/29676998

I ran across a discussion on the subject, which includes a spreadsheet linked in the first post which may be of interest to some here.

A Spreadsheet for Calculating Your Levine Phenotypic Age

 "An excellent paper by M. E. Levine, et al, entitled "An epigenetic biomarker of aging for lifespan and healthspan" describes a technique for combining nine blood-work values with calendar age to calculate your Mortality Score (probability of death in the next ten years) and your Phenotypic Age, i.e., your apparent biological age as implied by your blood variables.  The calculation procedure is rather arcane, involving non-obvious unit conversions, exponentials, and logarithms, so I have produced an Excel spreadsheet (LINK) for performing these calculations. ..."


https://forum.age-reversal.net/t/h4b2b5/a-spreadsheet-for-calculating-your-levine-phenotypic-age
 

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Wow....

Nobody here was interested enough to run their numbers?

It seems to be the most accurate of the phenotypic age and mortality predictors I've come across.

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 I tried it. My phenotypic age was 10 years younger than my actual age (54 -> 44). My phenotypic age would have been a lot lower (~40) if my MCV wasn't elevated (105), which as far as I can tell is almost a universal side effect of CR. 

--Dean

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Yeah, my MCV has gone up to just over 100, but it seems that if asymptomatic, elevated MCV is not an issue. You look younger than that 😄 😄

It looks like RDW has a large effect. Also CRP. I am 42.49 for phenotypic and 42.04 for DNAm age. I really wanted to be in my 30s.... 😄

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11 minutes ago, Ron Put said:

it seems that if asymptomatic, elevated MCV is not an issue.

Maybe... [1]

----

[1] J Am Geriatr Soc. 2013 Jan;61(1):84-9. doi: 10.1111/jgs.12066. Epub 2013 Jan 10.

Relationship between mean corpuscular volume and cognitive performance in older adults.

Gamaldo AA(1), Ferrucci L, Rifkind J, Longo DL, Zonderman AB. Author information: (1)Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, Maryland 21224, USA. Alyssa.Gamaldo@nih.gov Comment in J Am Geriatr Soc. 2013 Jan;61(1):155-7.

OBJECTIVES: To examine the relationship between erythrocyte mean corpuscular volume (MCV) and cognitive performance over time. DESIGN: Longitudinal. SETTING: Sample from the Baltimore Longitudinal Study of Aging (BLSA). PARTICIPANTS: Eight hundred twenty-seven participants from the BLSA (mean age 67, range 50-96).

MEASUREMENTS: Mean corpuscular volume and several other blood indices were measured, including hemoglobin, iron, ferritin, vitamin B12, folate, white blood cell count, albumin, and erythrocyte sedimentation rate. Cognitive performance was examined using neuropsychological measures of visual memory, verbal memory, language, attention, executive function, and global mental status.

RESULTS: High MCV levels were significantly associated with lower global mental status even after adjusting for potential confounders. High MCV levels were also significantly associated with high rates of decline on tasks of global mental status, long delay memory, and attention, even after adjusting for potential confounders.

CONCLUSION: The findings confirm a previous observation that larger erythrocytes in older adults are associated with poorer cognitive function. Anemia and inflammation do not appear to explain the relationship between MCV and cognition. Further research is needed to clarify the mechanisms behind this association.

© 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society. DOI: 10.1111/jgs.12066 PMCID: PMC3555566 PMID: 23301873 [Indexed for MEDLINE]

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Interesting.

They mention age-related narrowing of blood vessels as possible part of the mechanism. I'd guess that CR and low, plant based protein diet, may help ameliorate such effect.

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I would say that a higher level is an overall advantage:

Hematological parameters and all-cause mortality: a prospective study of older people.
Frąckiewicz J, Włodarek D, Brzozowska A, Wierzbicka E, Słowińska MA, Wądołowska L, Kałuża J.
Aging Clin Exp Res. 2018 May;30(5):517-526. doi: 10.1007/s40520-017-0791-y. Epub 2017 Jun 29.
PMID: 28664457 Free PMC Article
Abstract
BACKGROUND:
The effect of low and high concentration of some hematological parameters in the blood can have a negative impact on health.
AIM:
Therefore, we investigated the associations between hematological parameters and all-cause mortality among older people living in Poland.
METHODS:
The study was carried out among 75-80-year-old participants (n = 403) from Warsaw and Olsztyn regions, Poland. Information on lifestyle factors and food consumption were obtained at baseline (June 1, 1999) using a self-administered questionnaire. Red blood cell, haemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), and mean corpuscular haemoglobin concentration (MCHC) were determined. The data on deaths from all-causes were collected from the baseline until October 31, 2006. During an average of 7.4 years of follow-up, we ascertained 154 cases of death from all-causes.
RESULTS:
Compared with men in the lowest tertile of MCV, MCH, and MCHC, the multivariable hazard ratios (HRs) of all-cause mortality in those in the highest tertile were 0.35 (95% CI, 0.17-0.73), 0.32 (95% CI, 0.16-0.67), and 0.44 (95% CI, 0.22-0.88), respectively. In contrast, among women after combining the second and the third tertiles of MCV, MCH, and MCHC, the HRs were 2.01 (95% CI, 1.01-3.99), 1.71 (95% CI, 0.85-3.43), and 1.09 (95% CI, 0.62-1.94), respectively.
DISCUSSION/CONCLUSION:
We observed inverse associations between some hematological parameters and all-cause mortality among men, but not among women. This may be explained by a difference in iron metabolism, iron status, hormone regulations, or the occurrence of some diseases.
KEYWORDS:
Gender; Hematological parameters; Mortality; Older people; Prospective study

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Thanks Al. What seems strange is why, given the study you cite (in which higher MCV was associated with lower mortality, at least in men), the Levine Phenotypic Age equation suggests MCV is positively correlated with phenotypic age (i.e. higher MCV implies higher age).

Perhaps the Levine approach to estimating age from biomarkers isn't as good as Ron suggests.

And unfortunately, long lifespan is compatible with impaired cognitive performance, both of which may result from (or at least correlate with) elevated MCV. 

--Dean

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15 minutes ago, Dean Pomerleau said:

Perhaps the Levine approach to estimating age from biomarkers isn't as good as Ron suggests.

  --  Saul

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1 hour ago, Dean Pomerleau said:

...

Perhaps the Levine approach to estimating age from biomarkers isn't as good as Ron suggests.

...

Well, if one does a little research, its predictive abilities are rather good and better than most. It also jives with other research on the subject (e.g., https://onlinelibrary.wiley.com/doi/full/10.1111/acel.12557 )

As to increased MCV values, as I noted above, the key is being asymptomatic (although I ran into a study I'll cite below which seems to indicate otherwise). For instance, during fasting, MCV values generally increase, as folate, B-12 and iron are depleted. Chronic deficiencies in those would also trigger an increase in MCV. Rapid turnover of RBCs will also do it. RBCs also depend on glucose for survival, so very low glucose levels would impact them as well (not so in my case). Or B malabsorbtion. In my case, I was thinking of double checking my B-12, since my folate appears fine.

But it also appears rather well documented that increased MCV are predictive of mortality in many clinical instances. Here are a couple of examples:

The prognostic value of interaction between mean corpuscular volume and red cell distribution width in mortality in chronic kidney disease

 

 

Mean corpuscular volume levels and all-cause and liver cancer mortality

"Elevated MCV level was related to an increased risk of liver cancer mortality in men (aHR, 3.55; 95% CI, 1.75-7.21). Conclusions: This study suggests that the elevated MCV level in non-anemic cancer-free individuals was associated with increased all-cause mortality in both men and women, and with cancer mortality, in particular liver cancer mortality in men."

 

 

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Ron,

So perhaps, like it does with testosterone, CR push MCV in a direction that is associated with negative health outcomes in the "normal" population.  For example, perhaps elevated MCV is a early biomarker of certain cancers. But when elevated due to benign causes like CR or fasting, elevated MCV might not be predictive of bad outcomes - or at least one can hope.

--Dean

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