Chapter 181
Changing Aging — 18
There are other lifestyle features that have been assessed for pro- or antiaging properties. Early exposure to tobacco, as a fetus or during childhood, has been linked to accelerated epigenetic aging. The stress from major surgery increases epigenetic aging, and social stress facilitates immune aging.
Figure 12.8. Epigenetic aging clock favorably modified by exercise. Adapted from Steve Horvath et al., “Digitising the ageing process with epigenetic clocks,” Lancet 404, no. 10451 (August 2024): 423, https://doi.org/10.1016/s0140-6736(24)01554-x.
The relationship of hobby engagement with healthy aging was studied in more than ninety-two thousand people aged sixty-five years and older in sixteen countries with a consistent link to improvement. That brings to mind Mrs. L. R. and her hobbies of painting and jigsaw puzzles at the healthy and robust age of ninety-eight years. As does her optimism, which has been associated with 11 to 15 percent longer lifespan. Add to that her lack of isolation and social connectedness. A recent study of more than 280,000 people using an AI-processed electrocardiogram biologic aging metric indicated that the least isolated people had the slowest biological aging.
As reviewed in chapter 3, with aging, our sleep quality and circadian rhythm are disrupted. Epigenetic aging can be slowed (using PhenoAge as the metric) with better sleep health. Perhaps more surprisingly, the built environment has been found to have connections with biological aging, such as air pollution from traffic or disadvantaged neighborhoods characterized by poorly maintained roads, abandoned cars, and nonart graffiti.
INTERVENTIONS TO SLOW AGING
Modulating the aging process is all very well, but the prize many of us have in mind is actually reversing any functional declines. What can we say about that? Overall, the evidence is slight but intriguing, even exciting. Of course, I will start with rejuvenating the immune system.
We know by now how the age-induced changes to the immune system, or immunosenescence, are detrimental. In the animal model of defective DNA repair, immunosenescence can drive the aging of multiple organs, including the liver, kidneys, pancreas, and lungs. Through single-cell sequencing millions of immune cells of people at different ages, we’re now learning precisely which cells are affected with the aging process.
Three very different approaches have been assessed to reverse aging of the immune system. A combination of recombinant human growth hormone, metformin, and dehydroepiandrosterone was given to a small group of ten male participants aged fifty to sixty-five years; only growth hormone has a known effect on the thymus gland and its vital importance to T cell production. MRI revealed evidence of thymus regeneration in the male participants. Compared with baseline, there was a decrease in multiple inflammatory markers and a heightened immune response. Epigenetic age (by Horvath and GrimAge clocks) dropped a mean of one and a half years, with further reduction at one year follow-up. A few words on growth hormone as a potential intervention: although levels decline with age and supplementation improves muscle mass and bone density in older adults, it promotes insulin resistance, and there are no data to support a favorable impact on lifespan.