"Long-term calorie restriction in humans is not associated with indices of delayed immunologic aging" [eg PBMCs of CRONites do not have longer telomeres or lower Horvath DNAm age]. Why?

[Alex K Chen]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5389018/

Eric Verdin mentioned this.

https://blog.trudiagnostic.com/epigenetic-patterns/

https://www.medrxiv.org/content/10.1101/2021.09.21.21263912v1.full (CR non-significantly increases DNAm age on Horvath/Hannum clocks). They do help with DunedinPACE and GrimAge. These, again, are just for PBMCs (which may or may not be representative of cells elsewhere - CR is known to depress white blood cell count). But decreases in WBC count, I presume, would at least indicate that CR'd HSCs divide less, which would presumably better maintain their telomere lengths.

Edited January 9, 2023 by InquilineKea

[mccoy]

First link: Long-term calorie restriction in humans is not associated with indices of delayed immunologic aging: A descriptive study

In the article they used as markers of aging immunosenescence and telomeres length. There are a few issues which these parameters, mentioned by Morgan Levine in her book on aging. Also, as Horvath showed in one of his presentations online, there is no correlation between epigenetic aging and telomere length nor cells senescence, this appears to be a known fact.

Second link there is no indication of the original paper commented. There is no quantitative nor qualitative indication of the change in biological age by biological clocks after the period of dieting.

Third link: Effect of Long-Term Caloric Restriction on DNA Methylation Measures of Biological Aging in Healthy Adults: CALERIE™ Trial Analysis

It is strange that most clocks do not recognize a slowing of aging in those practicing CR, sometimes they exhibit an accelerating aging, whereas a couple of specific ones, derived from the Dunedin cohort, do. I remember Mike Lustgarten has already cited this in the other thread. A possible explanation is presented in the article. Sure there is a need of an accepted standardization for the use of specific clocks in specific aspects.

 

Quote

One possible explanation for why Pace of Aging measures were more sensitive to intervention as compared to the clocks is that the clocks, because they summarize aging related changes accumulated over the entire lifespan, may be less sensitive to interventions that slow aging, but do not substantially reverse it.

 

[Alex K Chen]

What causes "Pace of Aging" measures to change so rapidly? Are they located at sites that easily change methylation?

I think Horvath specifically went after CpG sites that measure *age* well, so naturally he went after CpG sites that are WAY less malleable than most other CpG sites.

[mccoy]

On 1/10/2023 at 12:58 PM, InquilineKea said:

What causes "Pace of Aging" measures to change so rapidly? Are they located at sites that easily change methylation?

I think Horvath specifically went after CpG sites that measure *age* well, so naturally he went after CpG sites that are WAY less malleable than most other CpG sites.

That depends on the clock and Horvath developed quite a few. A clock used for forensic purposes of course should be as precise as possible and reflect closely the chronological age, whereas a clock used to indicate biological aging needs data dispersion, since the difference from the regression line constitutes the defect or excess of years with respect to chronological age.

The clock from the Dunedin cohort, like PoA, as far as I could understand was developed by frequentistic analysis (statistical distributions) of samples of people of the same age, without attempting a multivariate regression. low percentiles were those looking younger, high percentiles those looking older, the average exhibited the people looking about their chronological age in a specific age cohort. What's interesting is that they also used  methods of age assessment based on perceptions from external people and partecipants (looking younger, looking older , feeling younger or older, and so on).

[Alex K Chen]

New study came out, shows they don't affect 2nd-generation epigenetic aging clocks

 

Edited February 10, 2023 by InquilineKea

[mccoy]

I think Mike Lustgarten already mentioned that, the clocks developed from the Dunedin studies in New Zealand for some reason are suited to CR practitioners whereas other clocks aren't. Going to read the article ASAP

[Alex K Chen]

There are new DNAm aging clocks that are better at capturing this effect now..