DNA methylation aging clocks

Excerpt

A key question in biology is to understand why and how we age. Alongside this, the unprecedented gain in the average lifespan in humans, since the mid-twentieth century, has dramatically increased both the number of older people and their proportion in the population. This demographic phenomenon is changing our societal make-up, from only ~130 million being 65 years or older (~5% of the world population) in 1950, to a predicted ~1.6 billion people (~17%) by 2050.

However, the success in reducing mortality has not been matched with a reduction in chronic disease. This leads to the undesirable outcome of many years of this prolonged lifespan being spent in ill health, with an associated massive health care burden. Increasing the productivity and reducing the disease affliction in these extended years would be clearly beneficial for both the individual and society.

This aim of maximizing the “healthspan” makes obtaining accurate measures of aging-related pathology essential, to gauge its speed, decipher the changes that occur, and potentially unlock how aging acts as a disease risk factor. There is considerable population variation in the rate at which people visibly age as well as become impaired by age-related frailty and disease. Measurement of this relative “biological” aging may allow pre-emptive targeted health-promoting interventions, perhaps in a personalized and disease-specific fashion. It would also aid in testing interventions that attempt to modulate the aging process.

The cellular and molecular hallmarks of aging include changes associated with cell senescence, dysregulated nutrient sensing, and stem cell exhaustion, among others. Therefore, many biological measures, such as p16ink4a tissue levels, circulating CRP, creatinine, and fasting glucose, as well as telomere length all correlate with aging.

In this decade, we have discovered the remarkable power of epigenetic changes to estimate an individual’s age. Epigenetics encapsulates the chemical modifications and packaging of the genome that influence or indicate its activity, with strict definitions requiring inheritance through mitotic cell division. Observations of age impacting on this mechanism have been reported for more than 50 years and suggested a role in age-related disease.

However, the association between epigenetic modifications and age became most starkly apparent with the arrival of the first high-throughput arrays measuring DNA methylation. These high-resolution data enabled the construction of extremely accurate age estimators, termed “Epigenetic” or “DNA methylation clocks”.

FULL TEXT: BMC Genome Biology



Facing up to the global challenges of ageing

Abstract

Longer human lives have led to a global burden of late-life disease. However, some older people experience little ill health, a trait that should be extended to the general population.

Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan. Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals and drugs can all improve late-life health in animals.

Application to humans will require better biomarkers of disease risk and responses to interventions, closer alignment of work in animals and humans, and increased use of electronic health records, biobank resources and cohort studies.

FULL TEXT: Nature