Aging Biomarker

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Biomarkers of Ageing

Ageing is a dynamic process that does not only depend on the species, the genotype and phenotype, but is also dependent on environmental influences. The ageing/age of an individual can not yet be directly determined.

Biomarkers of ageing are biomarkers that better predict functional capacity at a later age than chronological age [Baker+Sprott:1988]. Biomarkers of ageing would give the true biological age, which may be different from the chronological age. Validated biomarkers of ageing would allow for testing interventions to extend lifespan, because changes in the biomarkers would be observable throughout lifespan of the organism [Baker+Sprott:1988]. Ideally, biomarkers of ageing should assay the biological process of ageing and not predisposition to disease, should cause a minimal amount of trauma to assay in the organism, and should be reproducibly measurable during a short interval compared to the lifespan of the organism [Baker+Sprott:1988].

Although greying of hair increases with age [Van_Neste+Tobin:2004], hair greying cannot be called a biomarker of ageing. Similarly, skin wrinkles and other common changes seen with ageing are not better indicators of future functionality than chronological age. Biogerontologists have continued efforts to find and validate biomarkers of ageing, but success this far has been limited. Although maximum lifespan would be a means of validating biomarkers of ageing, it would not be a practical means for relatively long-lived species such as humans. Levels of CD4 and CD8 memory T cells and naive T cells have been used to give good predictions of the expected lifespan of middle-aged mice [Harrison:2011] [Miller:2001].

Biological clocks, for example the epigenetic clock, are promising biomarkers of ageing [Horvath:2013]. Ideally changing this biomarker itself is known to increase the lifespan. Though this is not necessary. The methods should be non-invasive or as less invasive as possible. If erythrocytes can be obtained, one could for instance measure Glutathione disulfide/Glutathione (GSSG/GSH) ratios (i.e. oxidation state of glutathione). Also circadian parameters might be interesting, as the circadian clock is disturbed as one gets older and interventions that extend the lifespan, such as dietary restriction, make that this clock tick much more robust. It is of particular interest to establish methods that can be automated so that they are easy to be taken continuously or periodically and can be scaled to many individuals. A comprehensive inventory of possible biomarkers of ageing need to be established to better assess the impact of established or potential novel manipulations of ageing.

References

[Baker+Sprott:1988](1, 2, 3) Baker, G T 3rd & Sprott, R L (1988). 'Biomarkers of aging.' Experimental gerontology. 23(4-5), pp. 223-39.
[Van_Neste+Tobin:2004]Van Neste, Dominique & Tobin, Desmond J (2004). 'Hair cycle and hair pigmentation: dynamic interactions and changes associated with aging.' Micron (Oxford, England : 1993). 35(3), pp. 193-200.
[Harrison:2011]David E. Harrison (2011) 'Life span as a biomarker'.
[Horvath:2013]Horvath, Steve (2013). 'DNA methylation age of human tissues and cell types.' Genome biology. 14(10), pp. R115.
[Miller:2001]Miller, R A (2001). 'Biomarkers of aging: prediction of longevity by using age-sensitive T-cell subset determinations in a middle-aged, genetically heterogeneous mouse population.' The journals of gerontology. Series A, Biological sciences and medical sciences. 56(4), pp. B180-6.


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