Chronological vs. Biological Aging and Diseaseby Brooklin White MS Candidate, Dietetic Intern News
Aging, as we understand it, is a biological process and not a disease directly. However, top aging researchers are proposing that aging should be considered a disease as it is the fundamental mechanism behind many diseases that we see today including cancer, osteoporosis, Parkinson’s, Alzheimer’s and heart disease (1). Throughout life our bodies accumulate toxins and DNA damage by unhealthy air quality, poor diets, sedentary lifestyles, high stress levels and poor sleep quality – all of which wear down our organs and make us more susceptible to disease. For example, saturated fat in small amounts can be processed by the body and thus causes little to no harm. When high amounts of saturated fat are consumed over the course of 10, 20 or 30+ years however, the body’s ability to clear out this accumulation of fat worsens and this plaque buildup in the arteries leads to atherosclerosis, strokes and cardiovascular diseases. In Alzheimer’s disease, unhealthy lifestyles such as poor diets, lack of exercise and lack of sleep can prevent the proper clearing of amyloid-beta and thus creates plaques and tangles in the brain, leading to neurodegeneration (2)(3)(4). Although it seems that pain medication and chronic diseases are inevitable aspects of aging, the science implies a different story.
Aging as a Disease
If aging is truly the root cause of all of these diseases then, can we prevent them by addressing aging head on? Researchers say yes, although pinpointing the true root cause of aging is not so simple. In Dr. David Sinclair’s book, Lifespan, he discusses nine hallmarks of aging that must be addressed in order to progress healthfully into old age. Those hallmarks are:
- Genomic instability caused by DNA damage
- Shortening of the protective chromosomal endcaps called telomeres
- Alterations to the epigenome that controls which genes are turned on and off
- Loss of healthy protein maintenance, proteostasis
- Deregulated nutrient sensing caused by metabolic changes
- Mitochondrial dysfunction
- Accumulation of senescent cells (which inflame healthy cells)
- Exhaustion of stem cells
- Altered intercellular communication and the production of inflammatory molecules
If we can address these hallmarks and slow down aging, we can prevent chronic diseases and extend healthspan and longevity. However, Dr. Sinclair proposes that the true cause of aging lies even further upstream of these nine hallmarks and is based on the loss of both DNA and epigenetic information. Although most doctors and scientists have never thought about why we age or how to treat aging directly, the current research indicates that we should.
Genes and Epigenetics
Genes are the master regulators when it comes to lifespan. We know this because yeast live for 6 days, flies for 2 months, mice for 2 years and humans for 70+ years. DNA determines our unique genetic code and provides the fundamentals for organisms to develop, survive and reproduce. Epigenetic information on the other hand instructs newly formed stem cells on what type of cells they should be (liver, brain, kidney, eye, skin etc.) and how they should operate (should we grow, or should we repair? Should turn off certain features or turn them on?). Without epigenetic information, our cells would quickly lose their identity and our organs would cease to operate effectively (1). Alterations in epigenetic markers or epigenetic “noise” can accumulate in our cells and are caused from unhealthy environmental factors, such as excess sun exposure, smoke exposure and poor food quality. The accumulation of this epigenetic noise doesn’t just measure aging but helps to cause it (1).The way our genes are expressed through environmental factors thus determines the rate at which we age.
This process has been referred to as the Information Theory of Aging. This epigenetic chaos eventually causes our healthy cells to become ‘senescent’ cells which are unable to divide, refuse to die, create reactive oxygen species, and continue to release panic signals that inflame surrounding healthy cells (5). Small amounts of senescent cells can be beneficial for the body, however as they help with tumor suppression, wound healing and protection against tissue fibrosis. It is when large amounts of senescent cells start to accumulate that leads to aging and disease. These senescent cells accumulate in response to telomere erosion, DNA damage, oxidative stress and oncogenic (cancer) activation (6). Clinical studies have shown that consumption of plant foods, such as almonds and brussels sprouts may protect against DNA damage by boosting our DNA repair mechanisms (7)(8). Additional research has shown that those who eat high levels of fruits and vegetables have lower levels of oxidative DNA damage than those who eat low amounts of fruits and vegetables and high amounts of processed foods (9)(10). Current research is being conducted by Dr. Sebastian Brandhorst at the University of Southern California to determine if the fasting-mimicking diet (FMD)aids in the removal of these old senescent cells (11). If we kill off these senescent cells or prevent them from accumulating, we can keep our tissues healthier for much longer and thus reverse or slow down our biological aging (1).
It is now understood that individuals with the same chronological age may vary in their rate of aging, indicating that biological age is more beneficial in determining health status. Biological age is simply a state of physical and physiological function that refers to how healthy a person’s body is functioning. Biological age is determined by nine biochemical markers: C-Reactive Protein, albumin, creatinine, glucose, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase and white blood cell count(12). This new measure of aging has been shown to be highly predictive of mortality for both healthy and unhealthy populations, even after adjusting for chronological age (12).
The concept of organ reserve is the notion that our organs are exceptional at clearing out toxins and maintaining functional capacity when we are young, but slowly start to lose their stamina as we age due to increasing amounts of epigenetic noise (13). The rate at which we lose our organ reserve is what shapes our individual aging processes. It has been shown that individuals lose organ reserve at different rates and thus, age differently (14). Healthy choices in food, moderate exercise, minimal stress and plenty of sleep for example, are all ways to maintain organ reserve, limit epigenetic noise, and keep biological age low.
Aging for Alzheimer’s
Besides the various risk factors for Alzheimer’s Disease, such as poor diet, lack of exercise, lack of brain stimulation, lack of sleep, and genetics, aging remains the number one risk factor for developing the disease. Although we don’t yet have a solution to fully reverse aging, individuals have the opportunity to make lifestyle choices that promote cognition, healthspan and longevity. It might come as no surprise that those factors are the same touted by the Blue Zones, the Amos Institute and the Institute for Functional Medicine:
- Eat whole, nutritious plant foods
- Limit red meat and processed meat
- Reduce processed carbohydrate consumption
- Increase healthy fats
- Clean air/low toxic exposures
- Reduce stress
- Maximize sleep
- Incorporate moderate physical activity
- Don’t smoke
- Find a passion in life
- Foster strong social connections
- Incorporate the FMD
The success of science lies in extending the frontiers of knowledge, by thinking outside of the box and by challenging our own beliefs. The current understanding is that there is no law in biology that says we must age at the rate we do right now (1). Although science hasn’t found a cure for aging, it has showed us that it is not the genes we were born with but rather the environmental choices we make on a daily basis that control the rate of aging and progression of disease. Treating aging as a disease would allow clinicians to focus on the root cause of all chronic diseases, rather than trying to treat them one at a time. Preclinical studies, clinical studies, epidemiological studies and Blue Zone communities have shown us that our environment makes a huge impact on how our genes are expressed and that lifestyle factors, such as those incorporated in the Bredesen Protocol, play a crucial role on cognition, healthspan and longevity.
“What is a disease but a condition that prevents the body or mind from working normally? That is, after all, what aging is doing” – Dr. David Sinclair
- Sinclair, D. A., & LaPlante, M. D. (2019).Lifespan: Why we age—and why we don't have to. Simon & Schuster.
- van Praag, H. (n.d.). Lifestyle Factors and Alzheimer’s Disease.Brain Plasticity,4(1), 1–2.https://doi.org/10.3233/BPL-120418
- Beydoun, M. A., Beydoun, H. A., & Wang, Y. (2008). Obesity and central obesity as risk factors for incident dementia and its subtypes: A systematic review and meta-analysis.Obesity Reviews,9(3), 204–218.https://doi.org/10.1111/j.1467-789X.2008.00473.x
- Winer, J. R., Mander, B. A., Helfrich, R. F., Maass, A., Harrison, T. M., Baker, S. L., Knight, R. T., Jagust, W. J., & Walker, M. P. (2019). Sleep as a Potential Biomarker of Tau and β-Amyloid Burden in the Human Brain.Journal of Neuroscience,39(32), 6315–6324.https://doi.org/10.1523/JNEUROSCI.0503-19.2019
- van Deursen, J. M. (2014). The role of senescent cells in ageing.Nature,509(7501), 439–446.https://doi.org/10.1038/nature13193
- Regulski, M. (2017).Cellular Senescence: What, Why, and How.Wounds Research.Retrieved July 22, 2020, fromhttps://www.woundsresearch.com/article/cellular-senescence-what-why-and-how
- Hoelzl, C., Glatt, H., Meinl, W., Sontag, G., Haidinger, G., Kundi, M., Simic, T., Chakraborty, A., Bichler, J., Ferk, F., Angelis, K., Nersesyan, A., & Knasmüller, S. (2008). Consumption of Brussels sprouts protects peripheral human lymphocytes against 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and oxidative DNA-damage: Results of a controlled human intervention trial.Molecular Nutrition & Food Research,52(3), 330–341.https://doi.org/10.1002/mnfr.200700406
- Li, N., Jia, X., Chen, C.-Y. O., Blumberg, J. B., Song, Y., Zhang, W., Zhang, X., Ma, G., & Chen, J. (2007). Almond Consumption Reduces Oxidative DNA Damage and Lipid Peroxidation in Male Smokers.The Journal of Nutrition,137(12), 2717–2722.https://doi.org/10.1093/jn/137.12.2717
- Prado, R. P., Santos, B. F. dos, Pinto, C. L. de S., Assis, K. R. C. de, Salvadori, D. M. F., & Ladeira, M. S. P. (2010). Influence of diet on oxidative DNA damage, uracil misincorporation and DNA repair capability.Mutagenesis,25(5), 483–487.https://doi.org/10.1093/mutage/geq030
- Kraj, M., Valachovi, M., Pauková, V., & Dušinská, M. (2008).Effects of Diet and Age on Oxidative Damage Products in Healthy Subjects.57, 5.
- American Federation for Aging Research. (2017).The Irene Diamond Fund/AFAR Postdoctoral Transition Awards in Aging.https://www.afar.org/grantee-profiles/sebastian-brandhorst
- Liu, Z., Kuo, P.-L., Horvath, S., Crimmins, E., Ferrucci, L., & Levine, M. (2018). A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study.PLOS Medicine,15(12), e1002718.https://doi.org/10.1371/journal.pmed.1002718
- Fries JF. Aging, natural death, and the compression of morbidity.N Engl J Med. 1980;303(3):130-135. doi:10.1056/NEJM198007173030304
- Bland, J. S. (2014).The disease delusion: Conquering the causes of chronic illness for a healthier, longer, and happier life. HarperCollins.