Aging & Optimal Longevity Biomarkers
During the last few years, an effort has been made to better quantify biological aging. One of the first institutes to work on this project is the National Aging Institute and the N.I.H. Nhanes (Source). The European Mark-age brought together over 20 European countries to also participate in this endeavor, while a group of scientists in New Zealand recently looked at 18 aging biomarkers in a cohort of young adults that were followed for 12 years. (Cf. Daniel W. Belsky et al., Quantification of biological aging in young adults, PNAS, Jul 2015, 112 (30) E4104-E4110).
The National Health and Nutrition Examination Survey (NHANES) is a survey research program conducted by the National Center for Health Statistics (NCHS) to assess the health and nutritional status of adults and children in the United States, and to track changes over time. The survey combines interviews, physical examinations and laboratory tests
Genetic heterogeneity as well as environmental factors influence the rate of human ageing. To measure the true biological age of an individual and predict the onset of diseases, identifying age-related changes that serve as biomarkers is necessary.
Although many candidate biomarkers have been proposed, no single measurement has proven useful. This could be due to the multi-system nature of ageing which requires multiple parameters to be analysed at once. In this context, the EU-funded ‘European study to establish biomarkers of human ageing’ (MARK-AGE) study proposed to identify a set of biomarkers of ageing to measure biological age accurately.
To achieve this, MARK-AGE partners performed a large study of over 2 300 individuals of different ages from seven locations across Europe. Another study group contained subjects born from a long-living parent belonging to a family with long-living siblings.
All enrolled subjects provided anthropometric, clinical and social information. Physical examination included measurements such as body mass index, waist and hip circumference as well as blood pressure and heart rate. In addition, subjects donated peripheral blood for further genetic and immunophenytoping analysis.
A series of putative DNA-based markers were examined such as DNA methylation, DNA repair and chromosome length. At the protein level, researchers looked at certain protein modifications and signs of protein damage. Since immune responses diminish with ageing, a number of immunological parameters were also evaluated such as antibody and cytokine levels. The study additionally included assays for measuring markers of metabolism and oxidative stress.
Out of these biomarkers, ten were selected based on their ability to better correlate the biological with the chronological age in the population. The results of assaying for these biomarkers were subsequently used to calculate a score that served as a prediction of an individual’s biological age.
The long-term goal of the MARK-AGE study was to develop a mathematical model that could calculate one’s biological age utilising these 10 biomarkers. This could help develop novel strategies for preventing accelerated ageing for a healthier lifestyle.
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By comparison, many people develop health issues at relatively young ages. A recent study out of the University of Otago in New Zealand (the “Dunedin Study”) suggests that rates of aging can be measured even in relatively young adults
Which markers will serve us best as predictors of biological age? Studies outside of the Dunedin Study, such as the Baltimore Longitudinal Study of Aging (BLSA) use a different combination of biomarkers. The European Study to Establish Biomarkers of Human Ageing (MARK-AGE) used a combination of techniques to discover and test new biomarkers of aging. One of the greatest challenges for future clinicians will be to integrate these new DNA biomarkers of aging with those physiological and biochemical markers that are already in use today.
Biomarkers of aging are biomarkers that could predict functional capacity at some later age better than will chronological age. Stated another way, biomarkers of aging would give the true “biological age”, which may be different from the chronological age.
Validated biomarkers of aging would allow for testing interventions to extend lifespan, because changes in the biomarkers would be observable throughout the lifespan of the organism. Although maximum lifespan would be a means of validating biomarkers of aging, it would not be a practical means for long-lived species such as humans because longitudinal studies would take far too much time. Ideally, biomarkers of
Although graying of hair increases with age, hair graying cannot be called a biomarker of ageing. Similarly, skin wrinkles and other common changes seen with aging are not better indicators of future functionality than chronological age. Biogerontologists have continued efforts to find and validate biomarkers of aging, but success thus far has been limited. 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.
Advances in big data analysis allowed for the new types of “aging clocks” to be developed. The epigenetic clock is a promising biomarker of aging and can accurately predict human chronological age.[
Thanks to these and other studies, we now have at our disposal physical, biological and genetical biomarkers that can help us to assess at any given moment a person’s biological age. These evaluations can also help us to better address age-related diseases. In this Presentation, we will examine some of the best Longevity biomarkers including those from the Happiness Medicine Institute.
An epigenetic clock is a type of a molecular age estimation method based on DNA methylation levels. Pre-eminent examples for epigenetic clocks are Horvath‘s clock, which applies to all human tissues/cells, and Hannum’s clock, which applies to blood.
Horvath, S (2013). “DNA methylation age of human tissues and cell types”. Genome Biology. 14: R115. doi:10.1186/gb-2013-14-10-r115. PMC 4015143. PMID 24138928.
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a b University of California, Los Angeles (UCLA), Health Sciences (20 October 2013). “Scientist uncovers internal clock able to measure age of most human tissues; Women’s breast tissue ages faster than rest of body”. ScienceDaily. Retrieved 22 October 2013.