Those who complain of beginning to “feel old” in their mid-40s may not necessarily be victims of a gloomy imagination. A significant new study on human aging has found that molecular changes show “substantial dysregulation” at two points in an individual's lifetime — when they are 44, and again, at age 60 years. Researchers from Stanford University said the findings provided “valuable insight into periods of dramatic alterations during human aging.” Notably, the research findings also indicated that disease risks are non-linear in nature — that is, they do not increase proportionately as age increases. What the study found on aging The study, 'Nonlinear dynamics of multi-omics profiles during human aging', published in the journal Nature Aging, analysed cellular-level data of 108 participants of ages between 25 and 75 years — all residents of California in the United States. The subjects of the study were tracked for a median period of 1.7 years. Every three to six months, the researchers collected blood, stool, skin swab, oral swab and nasal swab samples, which were used to analyse proteins, lipids, stool microbiomes, skin microbiomes, etc. More than 5,000 samples were analysed in all. The researchers detected distinct molecules and biological processes around the ages of 44 and 60. The body’s immune regulation, as well as the breakdown and conversion of carbohydrates, shifted during the 60-year mark. And there were changes related to cardiovascular diseases and metabolism of alcohol and lipids (fatty compounds) at the 40-year transition. These findings are in line with some existing data in the US on major non-communicable diseases. For example, neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease also have “distinct turning points occurring around the ages of 40 and 65 respectively”, the study said. The study also found that the capacity to metabolise caffeine undergoes a “notable alteration”, both around age 40 and at age 60 years. Takeaways from study Aging is generally understood as the irreversible and gradual degradation of cells, tissues, and organs with time, leading to weakened functioning. Scientific research on aging often aims to understand how aging works, and what can be done to slow it down in humans. At a cellular level, aging reflects the damage which the body has sustained over a long period due to multiple reasons — from the Sun’s ultraviolet rays to the lack of adequate nutrition. Aging impairs the ability of cells — the building blocks of human biology — to divide and multiply, thus impacting growth and development. There is also an increase in pigments and fatty substances (lipids) inside the cells, affecting their functioning. However, the pace of aging varies greatly among living organisms. A 2019 study by researchers from the University of Oxford and the National University of Ireland Galway on animal life cycles noted that while “the turquoise killifish (a small fish that can complete its life cycle in 14 days) grow fast and die young,.the Greenland shark (a fish that glides around for up to 500 years), grow slowly and have extraordinarily long lifespans”. Also, the study noted, humans and Asian elephants have “long lifespans and face a relatively low risk of mortality until later ages”. While the ages between 45 and 55 are known to result in crucial biological changes in women due to the onset of menopause, the new study found there are other underlying factors as well, which imply a “common phenomenon in the aging process of both sexes”. The researchers said their findings are also important for understanding the molecular changes related to aging, and for timely diagnosis of diseases. This could help in ultimately identifying “therapeutic targets” for aging-related diseases to increase human healthspan, as opposed to lifespan. 'Healthspan' is the period of time for which humans are healthy. Michael Snyder, a co-author of the study, told The Washington Post that the findings could help induce people to make healthier and targeted lifestyle choices. “For example, if you know that your carbohydrate metabolism is going off — there’s something you can do about that: changing your diet,” he said. Limitations, questions The study sample is small, and restricted to a specific geography. Certain findings, say on caffeine metabolisation, could be either due to the body’s actual slowing capabilities at that age or to consumption-related habits, which are more behavioural in nature. The researchers also concede the short duration of sample collection, of less than two years. Xiaotao Shen, another co-author, told The Washington Post that the factors driving the changes at these particular ages are unknown. “If we can find the drivers of these changes, we may even be able to find ways to slow or even reverse the drivers of the aging at these two time points,” he said.
