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Defining the aging phenotype

Defining the aging phenotype

Image credit: https://youtu.be/Q1CwARpnfe8

By Shubhankar Kulkarni on Jul 28, 2020

Question: Can we come up with a cumulative age score that can be used as a proxy for aging?

In aging studies, there have been challenges of defining the most relevant phenotype as a comparator. There are differences in the study designs, across study populations or models, and certain genetic effects surface only at extreme ages. Lifespan does not correlate appropriately with the physiological age and hence there is need for another biomarker. Different studies define the aging phenotype differently:

  1. Number of years free of age-related psychological or physiological disease[1]
  2. Epigenetic status of the cells[2]
  3. Telomere length[3]
  4. Changes in metal isotopes[4]
  5. Changes in metabolites like NAD+[5]

Can we come up with a cumulative age score based on all these factors or is there any other highly significant factor that can be used as a proxy for aging? We need to normalize aging to something, which can be more of a universal factor that can be used in scientific empirical studies.

If we cannot, what are the reasons?

References

[1] Walter S, Atzmon G, Demerath EW, Garcia ME, Kaplan RC, Kumari M, et al. A genome-wide association study of aging. Neurobiol Aging [Internet]. 2011 Nov;32(11):2109.e15-2109.e28. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0197458011002107

[2] Horvath S, Pirazzini C, Bacalini MG, Gentilini D, Di Blasio AM, Delledonne M, et al. Decreased epigenetic age of PBMCs from Italian semi-supercentenarians and their offspring. Aging (Albany NY) [Internet]. 2015 Dec 15;7(12):1159–70. Available from: http://www.aging-us.com/article/100861

[3] Harley CB, Futcher AB, Greider CW. Telomeres shorten during ageing of human fibroblasts. Nature [Internet]. 1990 May;345(6274):458–60. Available from: http://www.nature.com/articles/345458a0

[4] Li X, Snyder MP. Yeast longevity promoted by reversing aging-associated decline in heavy isotope content. npj Aging Mech Dis [Internet]. 2016 Dec 18;2(1):16004. Available from: http://www.nature.com/articles/npjamd20164

[5] Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, et al. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (80- ) [Internet]. 2016 Jun 17;352(6292):1436–43. Available from: https://www.sciencemag.org/lookup/doi/10.1126/science.aaf2693

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