Stanford’s latest research: Be careful of “cliff-like aging” at 44 and 60 years old!

The original meaning of "衰" refers to a raincoat that protects against wind and rain. Since this kind of clothing is woven layer by layer from grass, "衰" is further extended to mean decreasing layer by layer, generally referring to weakening or degradation.

Aging is a gradual weakening process. However, whether observing the elderly around us or feeling it ourselves, there seems to be a critical point - once you cross this invisible threshold, your physical condition will suddenly decline sharply, almost like "turning gray overnight"?

This may not be a fantasy!

Recently, scientists from Stanford University and Nanyang Technological University discovered that human aging does not occur slowly and gradually, but rather we experience two "cliff-like aging" events around the ages of 44 and 60, which bring us into middle age and old age respectively.

44 and 60 years old

Important points in aging

This new research was published in Nature Ageing, a subsidiary of Nature.

The study followed up 108 individuals aged 25 to 75 from the United States (51.9% of whom were women) for several years, with the longest monitoring period for a single participant reaching 6.8 years. During this period, samples such as blood, feces, skin swabs, oral swabs, and nasal swabs were collected from the participants to form a multi-omics data set.

In short, these comprehensive and in-depth biological multi-omics data sets enable scientists to analyze the series of changes that occur in different molecules during human aging, and eliminate the interference caused by differences in weight, gender, and whether or not there is diabetes.

The study found that only 6.6% of molecules change linearly during human aging, while the vast majority of molecules (81.03%) undergo a sudden nonlinear change at a certain age. The same conclusion can be drawn by changing other analysis methods. This shows that we do not age gradually, but rather undergo major changes at certain specific ages.

The authors then further analyzed the changing trajectories of thousands of molecules throughout the aging process and plotted them into curves. The results are obvious - two clear peaks appeared, pointing to around 45 and 60 years old respectively. These two time points have become milestones in the aging process, bringing us into middle age and old age respectively.

It is worth noting that many indicators, including proteomics, transcriptomics, metabolomics, cytokines, and intestinal microbiome, fluctuate dramatically in similar age groups. This suggests that the changes associated with aging between 45 and 60 years old are not limited to the molecular and cellular levels of humans, but rather a full-level, holistic, and systematic change from the inside out.

44 and 60 years old

Specific manifestations of aging

When these changes are reflected at the level of body functions, they result in rapid changes in physical condition and disease risk.

In terms of cardiovascular system , the research team found that during the dramatic aging changes between the ages of 45 and 60, cardiovascular indicators such as coagulation cascade reaction, protease binding, protein activation, blood coagulation, and fibrinolysis have undergone significant changes. These indicators are involved in important processes such as maintaining blood flow, and their imbalance may become the culprit for the frequent occurrence of thrombosis and cardiovascular problems at this age.

In addition, the gradual increase in plasma phenylalanine levels, branched-chain amino acids, and changes in the metabolism of fats such as high-density lipoprotein, glycerophospholipids, and α-linolenic acid are closely related to the occurrence of cardiovascular diseases such as cardiac hypertrophy, fibrosis, and coronary heart disease.

Skin and muscles also age rapidly during these two stages.

The extracellular matrix is ​​mainly composed of collagen, elastin and glycosaminoglycans, which can provide structural stability, mechanical strength, elasticity and moisture to skin tissues and cells. During these two rapid aging stages, scientists observed changes in the structural components of the extracellular matrix, as well as increased cell lysis (which increases skin water loss) and actin disorders (affecting skin structure and function), which lead to rapid aging of the skin.

In terms of muscle, an imbalance in muscle structural composition is observed between the ages of 45 and 60. After the age of 60, muscle mass decreases rapidly.

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There are also some differences between the changes at 45 and 60 years old.

Around the age of 45, the ability to metabolize caffeine, alcohol, and fat will decline with aging. In particular, the ability to metabolize alcohol will decline rapidly after the age of 40. Therefore, after the age of 40, it is best to appropriately adjust the intake of alcohol, fat, and caffeine.

At age 60, scientists mainly observed a rapid decline in the immune system, kidney function, and carbohydrate metabolism. Changes in indicators related to heart aging, atherosclerosis, type 2 diabetes, and blood oxygen carrying capacity were also more dramatic, meaning they were more susceptible to related diseases. This is consistent with many previous research results.

The study also found that pathways related to DNA damage repair, peptidyl lysine acetylation, and histone acetylation tend to increase before the age of 50. However, there will be a significant decline after the age of 50 to 56, and then it will be close to stability, and there will be no substantial changes until the maximum age in the study (75 years old). These three pathways are essential for maintaining genome stability, gene expression, and metabolic balance. This shows that the human body's DNA repair ability is enhanced before the age of 50, so that mutations can be repaired as much as possible to avoid the occurrence of tumors. However, the DNA repair ability decreases significantly between the ages of 50 and 56, and until the age of 75, gene mutations will accumulate faster than before the age of 50 and increase the risk of tumors.

Preventing aging

It’s important to develop these habits

While it is difficult to reappear as a teenager, research on aging can guide us to appropriate interventions to slow down the aging process and alleviate the resulting health problems.

Developing these habits will help us enjoy the world better in our 80s:

1

Healthy eating

Eat a balanced diet that includes protein, healthy fats, vitamins and minerals. Reduce your intake of foods high in sugar, salt and fat.

2

Regular exercise

Maintain muscle mass and bone density by regularly engaging in aerobic exercise and strength training, such as brisk walking, swimming, yoga, and weight training.

3

Get enough sleep

Ensuring 7 to 8 hours of high-quality sleep every night helps the body repair and recover.

4

Avoid bad habits

Quit smoking, limit alcohol consumption, and avoid excessive exposure to UV rays and environmental pollution.

5

Regular medical check-ups

Regular health check-ups are recommended to detect and treat chronic diseases early, especially after the age of 45. Specific check-ups may be added based on individual circumstances. For example, people at risk of cardiovascular disease may need more frequent blood pressure and lipid tests; people with a family history of cancer may need regular tumor marker tests or imaging tests.

6

Proper nutritional supplementation

Depending on individual needs, appropriate supplementation with antioxidants, vitamin D, and other nutrients that may help delay aging.

7

Lifelong Learning

Keep your brain active to prevent cognitive decline by reading, learning new skills, or engaging in intellectual activities.

References

[1] Fu Yonghe, Li Lingpu, Xiang Guangzhong (eds.). The Cultural Origins of the Evolution of Chinese Characters (Part 2)[M]. Guangzhou. Guangdong Education Press. 2012.12.1160-1161

[2] Shen X, Wang C, Zhou X, et al. Nonlinear dynamics of multi-omics profiles during human aging. Nat Aging. Published online August 14, 2024. doi:10.1038/s43587-024-00692-2

Planning and production

Author: Ai Yujie, PhD candidate in genomics at the Chinese Academy of Sciences

Review | Tang Qin, Director of the Science Popularization Department of the Chinese Medical Association, National Health Science Popularization Expert

Planning｜Yang Yaping

Editor: Yang Yaping

Proofread by Xu Lailinlin