Young blood + old blood


Many readers will recall the results of the past few years that claim that infusion of young-animal plasma into aged animals seems to have many beneficial effects. Of course, this field is well stocked with controversy. Not everyone believes the results, from what I can see (although, for what it’s worth, there seem to be an increasing number of papers on it). If they’re real, not everyone thinks that they can be readily extrapolated to humans. And even if they can, it doesn’t take very much thought to see a number of ethical implications as well.

There have been a couple of recent papers that will stir things up even more. This preprint from a multinational research team (UCLA and many others) details work on several “methylation clocks” of molecular aging. DNA is methylated (especially on cytosine residues) to a number of transcriptional effects, and the number and distribution of such methyl groups definitely change over the lifespan of most animals.

The Horvath lab at UCLA has made a specialty out of this epigenetic research area for some years now, and the changes in DNA methylation with aging seem pretty well established (even if quantifying them is trickier). This new paper draws on a large number of rat samples, with an overall methylation clock detailed, as well as more specific ones for brain, liver, and blood tissue. The addition of an even larger set of human tissue samples provides two more cross-species methylation clocks as well.

Previous work from the group has provided similar clocks for mice, which correlate well with known lifespan-extending interventions such as caloric restriction (reviewed here).

FULL TEXT: Science Translational Medicine

DNA methylation aging clocks


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