Aside from chronological age, the biological age in adults is related to health and resilience within the face of disease. Children may additionally be susceptible to health complications if their biological age exceeds their chronological age. A brand new research paper published within the journal Computational and Systems Biology, Epidemiology and Global Health explores how child development pertains to two latest candidate markers of biological age.
Study: Associations of 4 biological age markers with child development: a multi-omic evaluation within the European HELIX cohort. Image Credit: Kateryna Kon / Shutterstock
Introduction
Geroscience is predicated on the hypothesis that biological aging causes the breakdown of bodily processes, leading to multiple disease conditions dismissed as a part of old age. Many scientists have tried to discover markers of biological aging to offer a foundation for preventive interventions that would slow this downward trend and preserve health in later life.
Telomere length is a commonly used marker of biological age, directly reflecting one among the basic Hallmarks of Aging. It’s now being supplemented by high-throughput omics, examining epigenetic, transcriptional, translational, and metabolic pathways that change roughly uniformly with molecular-level aging.
These are unified to derive biological clocks and global assessments of cellular aging. Accelerated aging, which is the difference between predicted and chronological age, is a marker of age-related diseases and mortality risk.
One such style of clock is the Horvath clock and others, all based on DNA methylation. These have been further developed by integrating other clinical biomarkers and mortality data to yield second-generation clocks.
Child development and aging are related in a cause-effect manner, in line with the developmental origin of health and disease hypothesis. Healthy development thus builds up a greater stock of physical, cognitive, and mental health, which is reflected in a more prolonged period of healthy living in later years. That is explained by the flexibility to sustain one’s capabilities at suprathreshold levels for an extended period following the onset of late-adulthood-related decline.
Consistent with this postulate, Horvath’s DNA methylation clock shows a normal, unidirectional trend of change in the extent of methylation throughout life but faster in childhood. Some researchers consider that accelerated DNA methylation aging may thus be helpful in increase biological capital for an extended period of excellent health as life goes on.
That is in contrast with the importance of accelerated DNA methylation age in adults, which could reflect reduced biological capital, being the results of increased efforts to repair the wear and tear and tear on the cells attributable to external and intrinsic aspects operating during every day life.
Telomere shortening is taken into account an unfavorable marker, a response to early cell damage which will persist in maturity. Biological clocks based on omics are latest in the sphere but may reflect actual biological age higher because they measure the actual life processes which might be expressed because the phenotype, unlike the telomere length and DNA methylation clocks.
The present study included about 1,200 children between the ages of 5 and 12 years. The multinational study provided data from participants within the UK, France, Spain, Norway, Lithuania, and Greece. All were European and a part of the Human Early Life Exposome (HELIX) study.
The researchers determined how biological age indicators were related to developmental outcomes in children, equivalent to growth, fat deposition, cognition, behavior, lung function, and the time of puberty.
They used multiple biological clocks, including those based on telomere length, DNA methylation, and gene expression, in addition to those derived from the degrees of varied proteins and metabolites. Particularly, they tested the transcriptome- and immunometabolic-based age for consistency with other clocks.
The immunometabolic clock incorporates 135 markers of metabolic and inflammatory function, each being the outcome of gene expression. The transcriptome clock was composed of virtually 1,500 genes. These clock-derived markers were expressed by way of the difference between the expected and chronological age (Δ age).
Study design schematic.
What did the study show?
The researchers were in a position to predict the chronological age appropriately using two latest biological clocks, the transcriptome, and immunometabolic clocks.
The biological age markers showed only weak associations with one another, confirming that they reflect different elements of aging.
A better birth weight was linked to a better Δ age by immunometabolic markers. Family affluence was linked to longer telomere lengths.
Girls had longer telomeres than boys. That is well-known to be the case in adult life, but its presence in children indicates a biological foundation, which mediates increased risk when males are faced with other health risk aspects.
Boys with shorter telomeres and better transcriptome Δ age were more prone to have higher BMIs, while transcriptome and DNA methylation Δ age in boys were linked to poorer behaviors. Conversely, transcriptome and immunometabolic Δ age in girls was more strongly related to higher attentiveness.
“Given observed sexual dimorphism in each developmental rates and biological age measures, it might be unsurprising that relationship between biological age and development also differs between the sexes.”
Meanwhile, the DNA methylation Δ age was increased in association with smoke exposure during gestation by passive or energetic maternal smoking. It was lower with children from socially secure families, while transcriptome Δ age was higher.
All of the markers of biological age are linked to higher body mass index (BMI) and fat mass. Conversely, every marker apart from telomere length was linked with increased height.
A better immunometabolic Δ age indicated higher odds for improved working memory, with less inattentiveness, in comparison with increased inattention with a better DNA methylation Δ age. The latter was also linked to greater externalizing behaviors and shorter telomeres.
What are the implications?
The scientists were in a position to derive two latest measures of biological age and test two established markers. Though poorly correlated with one another, all markers were linked to increased weight gain and fat deposition.
The transcriptome clock was found to correlate well with the expected chronological age, even on the second assessment six months later. Thus, gene expression is closely related to age. Nevertheless, this clock correlated poorly with developmental outcomes aside from fat deposition and growth.
This means the necessity for clocks that reflect clinical situations somewhat than merely the chronological age.
BMI is a persistent marker of accelerated biological aging and emphasizes the role of dysfunctional metabolism in age-related physiological decline. Interestingly, it was the only risk factor for poor health to be identified in association with accelerated aging measured by five biological clocks.
“Here we show that the link between BMI and multiple dimensions of accelerated ageing can also be apparent in children.” All Aging Hallmarks bear a detailed correlation with energy-nutrition balance, with a high-fat mass being consistently linked to premature death.
This might be since the body prioritizes anti-aging pathways of cell repair when faced with limited nutrient availability, in place of growth and metabolism pathways. Increased fat deposition can also be a source of inflammation and oxidative stress, related to the shortening of telomeres and increased rates of DNA methylation.
As well as, children with accelerated DNA methylation age and immunometabolic age tended to be taller than others. This corroborates earlier studies.
While this might indicate a greater growth environment, more evidence is required to rule out an hostile facet of increased height gain. As an illustration, rapid gain in height could increase wear and tear on cells, and a few studies indicate that with excessive early height, life expectancy drops.
The immunometabolic age was also linked to more mature cognitive skills, equivalent to working memory and attentiveness. This will likely indicate higher immune and metabolic maturity and higher overall development.
As with adults, children also experience biological aging across a broad spectrum. Increased fat deposition correlates with faster biological aging. Again, while accelerated DNA methylation age and telomere attrition in children might be potentially detrimental to their future health, advanced immunometabolic age might profit the kid’s development in some respects.