Chapter 173
Changing Aging — 10
The critical role of the gut microbiome in modulating our immune response has been emphasized throughout the book, but it extends from that into the whole aging process. Its composition differs in centenarians with youth-associated profiles of bacteria and viruses. In a study of more than nine thousand individuals, a microbiome pattern, such as depletion of Bacteroides, was associated with healthy aging. A gut microbial age metric was derived from more than ten thousand people aged forty to ninety-three years and correlated with the risk of cardiovascular disease over extended follow-up. The gut microbiome was profiled for correlation with frailty in more than eighteen hundred older adults, with specific bacterial species linked to high frailty scores and to clinical outcomes over the next two years. Fecal transplant of the gut microbiome from young mice to old mice improved cognitive behavior. In the opposite direction, transplants from old to young mice markedly promoted inflammation and inflammaging. These and many other experiments anchor the gut microbiome as a key player in the aging process.
Now that we’ve briefly reviewed the twelve biological hallmarks of aging, we’re ready to zoom in on the biomarkers that can be used to quantify our age.
BODY-WIDE BIOMARKERS OF AGING
The first epigenetic predictor of age, published back in 2011, could predict a person’s chronological age to within five years. It used saliva samples in thirty-four twin pairs assaying 88 CpG sites for DNA methylation. Recall that CpG sites are methyl groups attached to cytosine nucleotides. Two epigenetic clocks were published a couple of years later, one by Gregory Hannum and colleagues using blood in nineteen people with 71 CpG sites, and Steve Horvath (a coauthor of the two other preceding papers) using 353 CpG sites in multiple tissues for a clock, coined DNAmAge, that has “a high tick rate until adulthood, after which it slows to a constant tick rate.” These epigenetic clocks have been further refined over the years, with three major ones now being used extensively in research (DNAm PhenoAge, DNAm GrimAge, and DunedinPACE). The DNAm PhenoAge clock predicts biological age from DNA methylation, chronological age, and clinical parameters (including lab tests of albumin, creatinine, glucose, C-reactive protein, lymphocyte percent, and white blood cell count) associated with mortality risk. Among almost 150,000 people from the UK Biobank, there was a higher PhenoAge in people born after 1965, such that their biologic age was outpacing their chronologic age.