Posted on by Dr. Francis Collins
How can you tell how old someone is? Of course, you could scan their driver’s license or look for signs of facial wrinkles and gray hair. But, as researchers just found in a new study, you also could get pretty close to the answer by doing a blood test.
That may seem surprising. But in a recent study in Nature Medicine, an NIH-funded research team was able to gauge a person’s age quite reliably by analyzing a blood sample for levels of a few hundred proteins. The results offer important new insights into what happens as we age. For example, the team suggests that the biological aging process isn’t steady and appears to accelerate periodically—with the greatest bursts coming, on average, around ages 34, 60, and 78.
These findings indicate that it may be possible one day to devise a blood test to identify individuals who are aging faster biologically than others. Such folks might be at risk earlier in life for cardiovascular problems, Alzheimer’s disease, osteoarthritis, and other age-related health issues.
What’s more, this work raises hope for interventions that may slow down the “proteomic clock” and perhaps help to keep people biologically younger than their chronological age. Such a scenario might sound like pure fantasy, but this same group of researchers showed a few years ago that it’s indeed possible to rejuvenate an older mouse by infusing blood from a much younger mouse.
Those and other earlier findings from the lab of Tony Wyss-Coray, Stanford School of Medicine, Palo Alto, CA, raised the tantalizing possibility that certain substances in young blood can revitalize the aging brain and other parts of the body. In search of additional clues in the new study, the Wyss-Coray team tracked how the protein composition of blood changes as people age.
To find those clues, they isolated plasma from more than 4,200 healthy individuals between ages 18 and 95. The researchers then used data from more than half of the participants to assemble a “proteomic clock” of aging. Within certain limits, the clock could accurately predict the chronological age of the study’s remaining 1,446 participants. The best predictions relied on just 373 of the clock’s almost 3,000 proteins.
As further validation, the clock also reliably predicted the correct chronological age of four groups of people not in the study. Interestingly, it was possible to make a decent age prediction based on just nine of the clock’s most informative proteins.
The findings show that telltale proteomic changes arise with age, and they likely have important and as-yet unknown health implications. After all, those proteins found circulating in the bloodstream come not just from blood cells but also from cells throughout the body. Intriguingly, the researchers report that people who appeared biologically younger than their actual chronological age based on their blood proteins also performed better on cognitive and physical tests.
Most of us view aging as a gradual, linear process. However, the protein evidence suggests that, biologically, aging follows a more complex pattern. Some proteins did gradually tick up or down over time in an almost linear fashion. But the levels of many other proteins rose or fell more markedly over time. For instance, one neural protein in the blood stayed constant until around age 60, when its levels spiked. Why that is so remains to be determined.
As noted, the researchers found evidence that the aging process includes a series of three bursts. Wyss-Coray said he found it especially interesting that the first burst happens in early mid-life, around age 34, well before common signs of aging and its associated health problems would manifest.
It’s also well known that men and women age differently, and this study adds to that evidence. About two-thirds of the proteins that changed with age also differed between the sexes. However, because the effect of aging on the most important proteins of the clock is much stronger than the differences in gender, the proteomic clock still could accurately predict the ages in all people.
Overall, the findings show that protein substances in blood can serve as a useful measure of a person’s chronological and biological age and—together with Wyss-Coray’s earlier studies—that substances in blood may play an active role in the aging process. Wyss-Coray reports that his team continues to dig deeper into its data, hoping to learn more about the origins of particular proteins in the bloodstream, what they mean for our health, and how to potentially turn back the proteomic clock.
 Undulating changes in human plasma proteome profiles across the lifespan. Lehallier B, Gate D, Schaum N, Nanasi T, Lee SE, Yousef H, Moran Losada P, Berdnik D, Keller A, Verghese J, Sathyan S, Franceschi C, Milman S, Barzilai N, Wyss-Coray T. Nat Med. 2019 Dec;25(12):1843-1850.
What Do We Know About Healthy Aging? (National Institute on Aging/NIH)
Cognitive Health (NIA)
Wyss-Coray Lab (Stanford University, Palo Alto, CA)
NIH Support: National Institute on Aging
Posted on by Dr. Francis Collins
More than half of U.S. adults take dietary supplements . I don’t, but some of my family members do. But does popping all of these vitamins, minerals, and other substances really lead to a longer, healthier life? A new nationwide study suggests it doesn’t.
Based on an analysis of survey data gathered from more than 27,000 people over a six-year period, the NIH-funded study found that individuals who reported taking dietary supplements had about the same risk of dying as those who got their nutrients through food. What’s more, the mortality benefits associated with adequate intake of vitamin A, vitamin K, magnesium, zinc, and copper were limited to food consumption.
The study, published in the Annals of Internal Medicine, also uncovered some evidence suggesting that certain supplements might even be harmful to health when taken in excess . For instance, people who took more than 1,000 milligrams of supplemental calcium per day were more likely to die of cancer than those who didn’t.
The researchers, led by Fang Fang Zhang, Tufts University, Boston, were intrigued that so many people take dietary supplements, despite questions about their health benefits. While the overall evidence had suggested no benefits or harms, results of a limited number of studies had suggested that high doses of certain supplements could be harmful in some cases.
To take a broader look, Zhang’s team took advantage of survey data from tens of thousands of U.S. adults, age 20 or older, who had participated in six annual cycles of the National Health and Nutrition Examination Survey (NHANES) between 1999-2000 and 2009-2010. NHANES participants were asked whether they’d used any dietary supplements in the previous 30 days. Those who answered yes were then asked to provide further details on the specific product(s) and how long and often they’d taken them.
Just over half of participants reported use of dietary supplements in the previous 30 days. Nearly 40 percent reported use of multivitamins containing three or more vitamins.
Nutrient intake from foods was also assessed. Each year, the study’s participants were asked to recall what they’d eaten over the last 24 hours. The researchers then used that information to calculate participants’ nutrient intake from food. Those calculations indicated that more than half of the study’s participants had inadequate intake of vitamins D, E, and K, as well as choline and potassium.
Over the course of the study, more than 3,600 of the study’s participants died. Those deaths included 945 attributed to cardiovascular disease and 805 attributed to cancer. The next step was to look for any association between the nutrient intake and the mortality data.
The researchers found the use of dietary supplements had no influence on mortality. People with adequate intake of vitamin A, vitamin K, magnesium, zinc, and copper were less likely to die. However, that relationship only held for nutrient intake from food consumption.
People who reported taking more than 1,000 milligrams of calcium per day were more likely to die of cancer. There was also evidence that people who took supplemental vitamin D at a dose exceeding 10 micrograms (400 IU) per day without a vitamin D deficiency were more likely to die from cancer.
It’s worth noting that the researchers did initially see an association between the use of dietary supplements and a lower risk of death due to all causes. However, those associations vanished when they accounted for other potentially confounding factors.
For example, study participants who reported taking dietary supplements generally had a higher level of education and income. They also tended to enjoy a healthier lifestyle. They ate more nutritious food, were less likely to smoke or drink alcohol, and exercised more. So, it appears that people who take dietary supplements are likely to live a longer and healthier life for reasons that are unrelated to their supplement use.
While the study has some limitations, including the difficulty in distinguishing association from causation, and a reliance on self-reported data, its findings suggest that the regular use of dietary supplements should not be recommended for the general U.S. population. Of course, this doesn’t rule out the possibility that certain subgroups of people, including perhaps those following certain special diets or with known nutritional deficiencies, may benefit.
These findings serve up a reminder that dietary supplements are no substitute for other evidence-based approaches to health maintenance and eating nutritious food. Right now, the best way to live a long and healthy life is to follow the good advice offered by the rigorous and highly objective reviews provided by the U.S. Preventive Services Task Force . Those tend to align with what I hope your parents offered: eat a balanced diet, including plenty of fruits, veggies, and healthy sources of calcium and protein. Don’t smoke. Use alcohol in moderation. Avoid recreational drugs. Get plenty of exercise.
 Trends in Dietary Supplement Use Among US Adults From 1999-2012. Kantor ED, Rehm CD, Du M, White E, Giovannucci EL. JAMA. 2016 Oct 11;316(14):1464-1474.
 Association among dietary supplement use, nutrient intake, and mortality among U.S. adults. Chen F, Du M, Blumberg JB, Ho Chui KK, Ruan M, Rogers G, Shan Z, Zeng L, Zhang. Ann Intern Med. 2019 Apr 9. [Epub ahead of print].
 Vitamin Supplementation to Prevent Cancer and CVD: Preventive Medication. U.S. Preventive Services Task Force, February 2014.
Healthy Eating Plan (National Heart, Lung, and Blood Institute/NIH)
National Health and Nutrition Examination Survey (Centers for Disease Control and Prevention, Atlanta)
U.S. Preventive Services Task Force (Rockville, MD)
Fang Fang Zhang (Tufts University, Boston)
NIH Support: National Institute on Minority Health and Health Disparities
Posted on by Dr. Francis Collins
Many older people who’ve survived a heart attack or stroke take low-dose aspirin every day to help prevent further cardiovascular problems . There is compelling evidence that this works. But should perfectly healthy older folks follow suit?
Most of us would have guessed “yes”—but the answer appears to be “no” when you consider the latest scientific evidence. Recently, a large, international study of older people without a history of cardiovascular disease found that those who took a low-dose aspirin daily over more than 4 years weren’t any healthier than those who didn’t. What’s more, there were some unexpected indications that low-dose aspirin might even boost the risk of death.