Changing Aging — 15

Other health factors that can accelerate brain aging were shown in a recent report that chronic knee pain from osteoarthritis, assessed by MRI and memory function, affected the hippocampus, thalamus, and several regions of the brain and manifested increased risk of dementia during follow-up.

After the brain, muscle has perhaps been the most extensively studied organ for impact of aging, with the advantage of being able to acquire healthy tissue across the lifespan. Muscle biopsies from seventeen participants aged twenty to seventy-five years enabled sequencing of more than ninety thousand single cells and single nuclei. Insights from this work told us about stem cell dysfunction, increased pro-inflammatory protein production, activation of the immune system, and loss of nerve supply.

For heart aging, studying macaques indicates that heart muscle cells get much bigger with age, twice the size as young monkeys’, along with increased production of pro-inflammatory proteins, fibrosis (scarring), and senescent cells. Somatic mutations of heart cells accumulate, exhibiting deficiencies in DNA repair, more than age-related changes in brain cells or lymphocytes. The biologic aging process of each organ, such as the brain, muscle, or heart, representative of other organs, can march to its own pace within a given individual. We also know, from compelling genetic evidence of interconnectedness, that “no organ system is an island.”

MODULATING THE AGING PROCESS

How might the aging process be influenced? There are two basic categories: lifestyle+ and pharmacologic interventions. Let’s start with lifestyle.

Some studies look at the overall impact of a healthy lifestyle that includes diet, physical activity, and sleep. In more than 350,000 UK Biobank participants followed for more than ten years, a polygenic risk score for lifespan was used to tease out the genetic component. For lifespan, genetics appeared to contribute about 20 percent, and a favorable lifestyle had an independent pronounced effect. Mitigating the genetic risk of a shorter lifespan, lifestyle added about five years of life. In a smaller study of more than eleven thousand individuals from four cohorts with a much longer follow-up of twenty-eight years, a healthy lifestyle metabolomic signature (predominantly lipid metabolism and strongly aligned with low BMI and healthy diet) was associated with a 25 percent increase in longevity (reaching age eighty-five and older) and a significant lower risk of all-cause mortality as well as cardiovascular and cancer mortality. The participants for both reports were predominately of white-European ancestry, limiting ability to extrapolate.

In a study of healthy lifestyle that followed twenty thousand participants in Japan over twenty-one years, there was considerable expansion of lifespan despite chronic conditions (diabetes, cardiovascular, kidney, cancer) even beyond those aged eighty years. A “dose-effect” was seen by the number of healthy lifestyles for diet, sleep, exercise, low alcohol intake, BMI, and no smoking (fig. 12.6). Similarly, in a study of nearly fifteen hundred Chinese centenarians, with matched controls of people who died before becoming centenarians, the highest healthy lifestyle score was linked to most likelihood of living to an average ninety-five years.