Ken Raj: Biological Age

We tend to think of age in terms of the number of years we have been alive — meaning our chronological age. But the year that you were born is not necessarily an accurate measure of your health or your life expectancy. We are coming to realize that a better predictor is your biological age – and that can be quite different from your chronological age. So how do you learn your biological age? And what can you do with this information?

In this episode of humanOS Radio, Dan Pardi speaks with Ken Raj. Ken is a Senior Scientific Group Leader at Public Health London, and has worked extensively with Dr. Steve Horvath of UCLA in developing and interpreting genomic biomarkers of aging. They are best known for developing the “epigenetic clock,” a tool that predicts life expectancy by examining age-related changes to DNA methylation, then using that information to calculate biological age in relation to chronological age. The epigenetic clock is able to predict life expectancy with remarkable accuracy, with a margin of error of plus or minus three years.

Epigenetic reprogramming

Lowering the epigenetic age

Several studies have shown that OSKM induction (where O stands for Oct4) lowers epigenetic age gradually.

Having discovered this gradual property of epigenetic reprogramming, we can now be cautiously optimistic that we will manage to find a safe therapeutic window (such as marked by a yellow box in the graph) – that is, a period of safe epigenetic rollback when the methylation profile of a cell has been returned to a younger state but the cell has not lost its functional characteristics (for example, a skin cell would remain a skin cell rather than getting dedifferentiated into a pluripotent cell).

READ MORE: Youthereum Genetics

Steve Horvath

Steve Horvath is a professor of human genetics and biostatistics at the University of California, Los Angeles. Horvath had a lifelong interest in solving an important problem in aging research: how do we measure aging?

The epigenetic clock

In 2011 Horvath and his collaborators at UCLA described the first age estimation method (epigenetic clock) for saliva based on chemical modifications of the DNA molecule known as DNA methylation. Two years later Horvath published an age estimator that applies to all tissues and cells of the human body.

This discovery, known as the Horvath epigenetic clock, was unexpected because cells differ greatly in terms of their epigenetic patterns. Recently, he has studied treatments that slow or even reverse aging in humans. He and his colleagues have demonstrated that the epigenetic clock predicts lifespan and is related to centenarian status, obesity, HIV infection, early menopause, progeria, and many other age related conditions.

Reversing (cellular) aging

Abstract

Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue and organismal levels. At the chromatin level, aging associates with progressive accumulation of epigenetic errors that eventually lead to aberrant gene regulation, stem cell exhaustion, senescence, and deregulated cell/tissue homeostasis.

Nuclear reprogramming to pluripotency can revert both the age and the identity of any cell to that of an embryonic cell. Recent evidence shows that transient reprogramming can ameliorate age-associated hallmarks and extend lifespan in progeroid mice. However, it is unknown how this form of rejuvenation would apply to naturally aged human cells.

Here we show that transient expression of nuclear reprogramming factors, mediated by expression of mRNAs, promotes a rapid and broad amelioration of cellular aging, including resetting of epigenetic clock, reduction of the inflammatory profile in chondrocytes, and restoration of youthful regenerative response to aged, human muscle stem cells, in each case without abolishing cellular identity.

EDITOR’S NOTE: brief exposure to Yamakana factors (proteins that are used to convert cells to stem cells) somehow reversed many of the epigenetic changes (errors) that accumulate with age, making ‘old’ cells ‘young’ again.