Aging is not a smooth and gradual process. For instance, around 6.5% of people aged between 40 and 59 have coronary artery disease, a prevalence which jumps to 19.8% for people aged 60 to 79. Research inspired by such observations and published in the journal Nature Aging, has found that aging occurs in at least two accelerated bursts, at ages 44 and 60. This finding emerged after the researchers conducted a longitudinal study of 108 people from diverse ethnic backgrounds, residing in California, aged between 25 years and 75 years (median, 55.7 years) and 51.9% of whom were female. They were tracked for a median period of 1.7 years, with the maximum follow-up period being 6.8 years. Previous work with this same cohort had found that there are four distinct “ageotypes” -metabolic, immune, hepatic and nephrotic-, that determine the rate at which a person’s kidneys, livers, metabolism and immune system age. This study extends that work, revealing how aging-related diseases and mortality risk seem to spike at certain ages. 

The Findings

The researchers, led by Prof. Michael Snyder, a geneticist and director of the Center for Genomics and Personalized Medicine at Stanford University, took blood, stool, skin swab, oral swab and nasal swab samples from the study participants and conducted multi-omics profiling on the samples. Sampling was conducted every 3 to 6 months when healthy. The study collected 5,405 biological samples, including 1,440 blood samples, 926 stool samples, 1,116 skin swab samples, 1,001 oral swab samples and 922 nasal swab samples. The participants had a body mass index (BMI) of between 19.1 kg m−2 to 40.8 kg m−2,with a median BMI of 28.2 kg m−2. The process acquired 135,239 biological features, providing the researchers with 246,507,456,400 data points. This extensive and exhaustive process allowed the researchers to study the molecular changes that emerge as a result of aging. Each participant’s omics data was aggregated and averaged across the healthy samples to give a mean value for that participant. The result is that the study has a very robust dataset, because they can detect a participant’s baseline and assess the longitudinal molecular changes. 

What Snyder and his fellow researchers found was that the amount of most molecules and microbes does not change in a gradual, linear way, rather, they are nonlinear. The largest shifts tend to occur when a person is in their mid-40s and early 60s. Snyder told CNN that, anecdotally, “people often get muscle injuries and see their fat accumulation hit in their 40s (related to lipid metabolism), and definitely sarcopenia (muscle loss) hit people in their 60s — this is a very big deal.” In fact, 81.03% of molecules showed changes in at least one age stage compared to the baseline. For many people, it is a surprise that one of these spikes is in the mid-40s. Initially, it was thought that results of this kind were skewed by women undergoing menopausal or perimenopausal changes. However, this study showed that men in their mid-40s also go through this aging spike. There must be other changes that are common to both men and women, that account for this aging spike in a person’s mid-40s. Indeed, 55 seems to be a transition point common to both men and women. 

The first wave of changes involve molecules tied to cardiovascular disease, lipid and alcohol metabolism during the 40-year transition. In the second wave, dysregulation of skin and muscle stability occurs in both crests. A prior study by researchers in Germany and the United States, found that aging also crests at age 78, but because the age range of this cohort was 25 to 75, this study was unable to verify that finding. 

So, broadly, people in their 40s start to experience significant changes in the abundance of the molecules related to alcohol, caffeine and lipid metabolism; cardiovascular disease; and skin and muscle. People in their 60s, on the other hand, experience changes to their carbohydrate and caffeine metabolism, immune regulation, kidney function, cardiovascular disease, and skin and muscle. 

Source: Nature Aging

It’s interesting that a lot of the shifting factors seem related to heart health. For example, CXCL5, a protein that has a role in atherosclerosis -the build-up of lesions in arterial walls-, increased in participants’ blood during their 40s and 60s. This age cohort also saw a decrease in the ability to metabolize caffeine, leading to a temporary increase in blood pressure. The declining ability to metabolize alcohol in that age cohort leads to blood pressure first decreasing and then rising. 

Another point of decline involves the pathway for producing unsaturated fatty acids, which diminishes at these two crests, making it harder to reduce “bad” cholesterol. 

Now, the study’s findings are only correlative, but they do help to explain which heart disease increases with age. 

Heart disease isn’t the only risk factor that rises with age: a person’s blood sugar levels increase in their 40s and 60s, suggesting a link to age-related type diabetes. 

We don’t yet know why these changes take place at these ages, or how much of a factor lifestyle plays. Another problem, if you like, of the study is that it took place with a cohort in a fairly wealthy part of the world where people enjoy long lives. The findings would be more robust if they were conducted in poorer parts of the world, or, indeed, in other parts of the world where people may share the same economic advantages, in order to see if lifestyle plays a part in these changes, and if the crests take place at the same points in a person’s life.