Points in Life Where Women Age Fastest Identified Using Biological Clocks

A new study has constructed an “aging clock” for the female body – information missing from previous studies of aging. The research recruited a cohort of 113 women and mapped 4 domains of biological aging – chronic inflammation, hormonal regulation, tissue fitness and lipid metabolism – that can together accurately measure female biological age. The study then used these clocks to measure the periods of life where that ticking accelerates and found that biological age increases faster for women in their 30s and 50s.

A multiomics clock

Research in recent years has identified that our chronological and biological ages can become disconnected as we move through life. New techniques can measure the biological variables underlying our health – including fats (using lipidomics), metabolites (metabolomics) and the genes our body decides to convert into proteins (transcriptomics). With these powerful tools, biological clocks have been set for various cohorts. But these clocks have tended to group men and women. A team of Chinese researchers, led by senior author Jing Qu, a principal investigator at the Chinese Academy of Sciences, noted that “sex-specific features of aging and longevity are widespread” and decided to generate a female biological aging clock.

They recruited 113 healthy volunteers between the ages of 20 and 66. They were assessed using a veritable assault course of tests – the research team recorded no fewer than 175 variables about their cohort, including muscle mass, bone density and lung expiratory volume. Samples of blood and feces were taken for multiomics profiling, giving the team a panopticon view of their cohort’s physiological status. They also had to complete a set of 5 action competence tests, which measured factors such as grip strength, and a 52-item questionnaire about their living habits.

Using this wealth of data, the team identified three groupings of parameters that changed markedly as people aged – lipid metabolism, circulating hormones and tissue function:

• Lipid markers, like blood cholesterol and low-density lipoprotein, generally increased with age
• Four of seven sex hormones measured highly correlated with age. Follicle-stimulating hormone and luteinizing hormone were the most positively correlated with increased age, while anti-Mullerian hormone levels decreased with age
• Markers of impaired tissue function – such as decreased bone density and increased serum alkaline phosphatase (a marker of liver damage) – increased with age

The next stage of analysis went deeper. They looked at their participants’ transcriptomes: a snapshot of the genetic information being converted into proteins in their bodies. The gene whose expression was most negatively correlated with age was LRRN3, which is expressed in immune cells called T cells. These cells react to the presence of pathogens in the body, and LRRN3 is particularly linked to naïve T cells, which are unspecialized to particular functions, such as increasing or dampening immune responses. Changes in the immune system were accounted for as the fourth significant age clock.

The team used their aging clocks to identify two periods of life when their female subjects aged more quickly – around the ages of 30 and 50. At 30, the team noted that lipid and hormone metabolism changes drove the aging process, while the changes at 50 were associated with menopause, and were described by the research team as being “much more dramatic”, with changes seen in hormone levels, immunity and metabolite function.

Can the ticking of these clocks be slowed? Or wound back? Noting the significant contribution of hormonal changes to aging in women, the team explored how hormone replacement therapy (HRT) might alter the aging clocks. The “scores” of aging that the clocks helped calculate were lowered in people who underwent HRT. This doesn’t mean that the treatment is a panacea for aging, the team note – HRT may increase the risk of cancer and blood clots.

The team concludes by acknowledging that their study relies on a single snapshot of each of their participants’ lives, which is less informative than a long-term analysis. But by delving into the ticking of our body clocks, the team have taken the first steps towards a detailed portrait of the aging female body.

Reference: Li J, Xiong M, Fu X et al. Determining a multimodal aging clock in a cohort of Chinese women. Med. 2023:4;1–24. doi: 10.1016/j.medj.2023.06.010