Aging experiences two peaks at ages 44 and 60

Generally, after the age of 60, the first signs of old age appear. Wearing glasses, hearing aids, muscle pain or higher risk of diabetes, the examples are numerous. However, a recent study published in the journal Nature Agingsuggests that our body experiences two “peaks of old age” associated with major molecular changes: in our sixties, but also in our mid-forties.

Michael Snyder and colleagues from the Department of Genetics at Stanford University of Medicine, USA, analyzed the levels of more than 135,000 molecules and microbes – reflecting the activity of cells and tissues – in 108 volunteers in good health aged 25 to 75. Each participant provided blood and stool biological samples every three to six months for a median of almost two years.

Result: significant changes in the levels of numerous molecules were observed at two distinct times, at 44 and 60 years on average (variations may occur depending on the individual). The aging process therefore seems to accelerate during these periods – the forties and late fifties would then constitute important time windows to closely monitor the evolution of a person’s health.

Digestive disorders and cardiovascular diseases

Here is an observation that seems to reflect common observations: hangovers are more difficult to manage, muscle injuries become more and more frequent after the age of 40, etc. According to Michael Snyder, the data provided by this study would help explain these physiological changes.

Unlike younger subjects, both those in their 40s and 60s showed molecular changes linked to weakness and loss of muscle mass, a decline in heart health and an insufficient ability to metabolize coffee. However, these two waves of aging must be distinguished. By midlife, the activity of cellular pathways involved in the breakdown of alcohol and fats is reduced – which could explain why, after forty, we sometimes find it more difficult to digest these compounds. Sixty-year-olds, on the other hand, have lower levels of several immune system molecules, such as inflammatory cytokines. In other words, their immune response is weakened. Added to this, there are also low levels of molecules linked to carbohydrate metabolism as well as the functioning of the heart and kidneys, a sign indicating that older participants may be more likely to suffer from type 2 diabetes, cardiovascular diseases and kidney problems.

Results to be confirmed?

These two waves of aging are similar to those that another research team identified in 2020 – which observed that at the ages of 35 and 65 subjects showed weakened immune systems.

But the conclusions of this recent work are not irrefutable. One hundred and eight participants is a rather small sample for drawing general conclusions. Especially since all these people live in the same Californian region of Palo Alto, which is hardly representative of the world’s population, points out Aditi Gurkar, who conducts research on aging at the University of Pittsburgh (and who is not involved in the present study). She adds that these people likely share a similar lifestyle – whether it’s diet, level of physical activity or type of environment – ​​which could have influenced the results.

At age 44, the enzymes that metabolize alcohol and lipids become fewer. Then, at age 60, our immune system weakens.

Furthermore, the study followed the participants over a short period – seven years maximum – which does not make it possible to predict how they will age in the long term. Researchers are therefore unable to determine whether the differences observed between age groups reflect true universal biological changes, or whether they are simple individual variations. For example, the 40- and 60-year-old subjects included in the experiment may have aged more quickly than other people of the same age in the general population, the researcher warns.

To confirm these results, the scientists believe that a larger study would be needed following the same participants throughout their lives. And combining subjects from more diverse ethnic backgrounds, from different socioeconomic classes, because biological aging – the accumulation of stress experienced by cells and tissues – varies considerably depending on many parameters. Additionally, collecting data on factors such as a person’s health status or disability could help better assess the extent to which age-related changes impact overall health.

A breakthrough in the medical field

Despite all this, one question remains unanswered; why do the ages of 44 and 60 seem like critical milestones to cross? While the reasons are not yet clear, the authors of the study put forward several hypotheses that they hope to confirm in the future. The decline of the immune system in our 60s could lead to a decline in organ health, says Michael Snyder. While the peak of old age observed at mid-forties coincides with hormonal changes, particularly linked to the beginnings of menopause for women. But this period alone cannot explain all of the biological changes observed, because men and women are affected in a similar way. Another plausible explanation: the decline in physical activity at this age…

But Michael Snyder remains optimistic. He believes these results could prove valuable in the medical field. For example, people in their 40s could benefit from blood tests to monitor their lipid levels, or practice regular physical activity to preserve the health of their hearts. The researcher also highlights the importance of early and regular screening for heart disease for people of this age who have already had health problems.

Despite its limitations, this study reminds us that our lifestyle choices, such as diet and physical exercise, are likely to influence our aging – in a positive or negative way –, explains Aditi Gurkar. And she adds that there is currently little work that includes participants of varying ages, or involves biological sampling as comprehensive as this.

This work also represents an important step toward establishing large-scale disease predictive models based on biological data. Armed with this data, researchers will be able to better understand how the body ages and how these changes are linked to certain diseases.