“Forever young, I want to be forever young.
Do you really want to live forever? Forever. Forever young.”
Forever Young, Alphaville
Every living thing ages, grows old, and dies. And yet, as humans, we resist aging. The anti-aging industry is growing at record rates, and some estimates suggest that the US anti-aging industry will be worth [$88 billion by 2025]. In other words, we spend a lot of money for the dream of being forever young.
Why do we want to be younger? Our risk of dying increases with age. For example, if you’re 50, your risk of dying is 3 times higher than if you’re 30.1 And at 60, it’s worse. In fact, our risk of dying doubles about every 8 years after the age of 60. Sounds ominous, doesn’t it? However, the current maximum lifespan is twice that 60-year mark (122 years old), and the evidence suggests it could go higher. That means that while we may be twice as likely to die, it doesn’t have to be that way. We could extend our lives if we only knew the magic combination of genetics and environment that leads to a long healthy life.
Can the Aging Process be Stopped?
A recent study out of the UK demonstrated that we cannot stop the aging process.2 This study examined aging across 7 generations of humans and non-human primates. It shows that aging is relatively stable between members of a species and that biology prohibits us from slowing aging too much.
We can’t stop aging, but perhaps we could slow it down – we could reduce the amount of suffering that goes with aging. Could we reduce frailty, memory decline and dementia, immunosenescence, pain, skin issues, mobility challenges, and hearing and tooth loss? Can we reduce the overall increase in disease that accompanies aging? If so, we could age gracefully.
What does the Microbiome have to do with Aging?
The microbiome could be a key to graceful aging and less frailty. Frailty, one of the main indicators of aging, is when people are more susceptible to stressors. A consensus statement from 2013 suggested that frailty is “diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”3 And microbiome health is related to frailty.
A study out of the UK evaluated 728 women from the TwinsUK cohort.4 They discovered that the less alpha diversity someone had, the more frail they were. This study adjusted for age, diet, alcohol intake, smoking, and BMI. This study suggests that doing things to increase our alpha diversity might diminish frailty. Interestingly, a previous study out of China didn’t make the same observation; they didn’t observe a relationship between alpha diversity and frailty.5 However, the Chinese study had only 27 participants. Instead, the smaller study showed that there was more beta diversity in the frailty group than in the control group. Remember that alpha diversity is diversity within an individual whereas beta diversity is diversity between people. Both of these studies suggest that the microbiome could be related to frailty.
How might the microbiome contribute to frailty? One mechanism could be through the microbiome-immune relationship. One aspect of frailty is increased vulnerability to disease and this can be immune-mediated.6 If we look at the cause of death in the elderly, historically it was infectious disease. Now it tends to be chronic disease, such as cancer, heart disease, and Alzheimer’s in high-resourced countries.7 We now know that the microbiome contributes to each of these both directly through microbial metabolites and indirectly through immune health.8-10
What can we start doing today to Age Gracefully?
If longevity is the goal, what are some of the things that have been shown to increase life-span? Perhaps the best data comes from fasting research. That’s right – we need to stop eating so much. Let’s start with caloric restriction. Eating less by 20-40% of calories increases the life span of everything from yeast and worms to mice and monkeys.11 If the average human calorie consumption is around 2000 calories per day, reducing it to 1600 calories or less could extend our life span based on the animal data. Interestingly, fasting may extend overall life-span, but increases susceptibility to particular infectious diseases like the flu.11
Reducing calorie intake shifts the microbiota – specifically, it changes the ratio of Firmicutes to Bacteroides to favor Firmicutes.12 That shift in microbiota influences the type of fat that we store, causing us shift our white adipose tissue to brown. As a result, we lose weight. It’s unclear at this point whether the weight loss, the microbiome shift, or some other factor (like reduction in oxidative stress) is involved in the increased longevity in this research. Additional research has shown that simply restricting protein – not overall calories – can cause a similar shift in longevity in young and middle-aged mice and humans. However, once we’ve reached the age of 65, protein restriction leads to frailty.11
“The health of the microbiome is critical to our health, our frailty, and our life span.”
C. elegans are a type of worm that are commonly used to study aging. C. elegans live for 18-20 days if nothing is done to manipulate their life-span. Researchers have studied the effects of herbs and nutrients that are thought to increase longevity in C. elegans. They culture the C. elegans with the herb or a placebo and look at the difference in the number of days the worms live. While most of the herbs increase the life-span of C. elegans, some stand out more than others. Rosemary (in particular the compound rosmarinic acid) can extend the life-span of C. elegans by 40%.13 That means a worm may live 28 days instead of 20. The most powerful herbal effect was from a component of green tea called ECGC. It expanded the C. elegans life-span by 47%!!!13 I’ll do the math for you. If we applied that life-span extension to humans, it means a life-span of 70 years become 100 years. Interestingly, all of the herbs that increased the life span of C. elegans also have an impact on the microbiome. Note that fasting/caloric restriction also increases the life span of C. elegans.
We can drink tea, eat rosemary, restrict our calories, and we still may not live as long as we hope. The fountain of youth is elusive. However, a few things are clear. The health of the microbiome is critical to our health, our frailty, and our life span. As we learn new ways to nurture our microbiome, the long-term results may be a healthier aging process.
“And when you fin'lly fly away, I'll be hoping that I served you well.
For all the wisdom of a lifetime, no one can ever tell.
But whatever road you choose, I'm right behind you win or lose,
Forever young. (Forever young)”
Forever Young, Bob Dylan
References
- Death rate by age and sex in the U.S. 2019. Statista. Accessed March 21, 2022. https://www.statista.com/statistics/241572/death-rate-by-age-and-sex-in-the-us/
- Colchero F, Aburto JM, Archie EA, et al. The long lives of primates and the ‘invariant rate of ageing’ hypothesis. Nat Commun. 2021;12(1):3666. doi:10.1038/s41467-021-23894-3
- Proietti M, Cesari M. Frailty: What Is It? Adv Exp Med Biol. 2020;1216:1-7. doi:10.1007/978-3-030-33330-0_1
- Jackson M, Jeffery IB, Beaumont M, et al. Signatures of early frailty in the gut microbiota. Genome Med. 2016;8:8. doi:10.1186/s13073-016-0262-7
- Zhang L, Liao J, Chen Q, et al. Characterization of the gut microbiota in frail elderly patients. Aging Clin Exp Res. 2020;32(10):2001-2011. doi:10.1007/s40520-019-01385-2
- Pansarasa O, Pistono C, Davin A, et al. Altered immune system in frailty: Genetics and diet may influence inflammation. Ageing Res Rev. 2019;54:100935. doi:10.1016/j.arr.2019.100935
- Jan 29 P, 2019. The U.S. Government and Global Non-Communicable Disease Efforts. KFF. Published January 29, 2019. Accessed April 6, 2022. https://www.kff.org/global-health-policy/fact-sheet/the-u-s-government-and-global-non-communicable-diseases/
- Matson V, Chervin CS, Gajewski TF. Cancer and the Microbiome—Influence of the Commensal Microbiota on Cancer, Immune Responses, and Immunotherapy. Gastroenterology. 2021;160(2):600-613. doi:10.1053/j.gastro.2020.11.041
- Mozaffarian D, Wu JHY. Flavonoids, Dairy Foods, and Cardiovascular and Metabolic Health: A Review of Emerging Biologic Pathways. Circ Res. 2018;122(2):369-384. doi:10.1161/CIRCRESAHA.117.309008
- Bhattacharjee S, Lukiw WJ. Alzheimer’s disease and the microbiome. Front Cell Neurosci. 2013;7. doi:10.3389/fncel.2013.00153
- Longo VD, Di Tano M, Mattson MP, Guidi N. Intermittent and periodic fasting, longevity and disease. Nat Aging. 2021;1(1):47-59. doi:10.1038/s43587-020-00013-3
- Li G, Xie C, Lu S, et al. Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota. Cell Metab. 2017;26(5):801. doi:10.1016/j.cmet.2017.10.007
- Okoro NO, Odiba AS, Osadebe PO, et al. Bioactive Phytochemicals with Anti-Aging and Lifespan Extending Potentials in Caenorhabditis elegans. Molecules. 2021;26(23):7323. doi:10.3390/molecules26237323