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Feature Article: July 2020 – Aging as Molecular Damage Accumulation: the Role of Age Management Practitioners

e-Journal Featured Articles July 18, 2020

Aging as Molecular Damage Accumulation: the Role of Age Management Practitioners

Isabela M. B. David, M.D.

A number of theories have been proposed in an attempt to explain the process of aging. In the end, they fall into two main categories. The first is based on concepts holding that aging is programmed. The second defines the aging process as accumulation of damage. They are not necessarily mutually exclusive(1). 

What we do know is that aging is associated not only with the buildup of metabolic by-products, but also with the dysregulation of regulatory pathways(1). For example, aging upsets the balance between pro and anti-inflammatory components, promoting chronic inflammation(1, 2, 3). The causality between such inflammatory processes and age-related disorders has been well established(1).

The accumulation of non-degradable material can occur in the intra and extracellular environments(1). Among the extracellular deposits found in humans, cholesterol-containing plaques and their oxidised derivatives in blood vessels are worth mentioning, as well as protein polymers, such as β-amyloid in the central nervous system (1, 4, 5). In this context, it is good to remember that Reactive Oxygen Species (ROS) play a detrimental role in cellular functioning during aging, in particular within the mitochondria, but yet they certainly have a beneficial role in other pathways(1, 6). 

Metabolic waste also includes spontaneously modified sugar-bound proteins, mainly glucose molecules. Glycation involves interaction between the amino groups of lysine and the aldehyde groups of glucose via a Schiff base reaction. It is followed by rearrangement of the double C=N-bond, known as Amadori products, to yield a wide range of advanced glycation end-products (AGEs)(1, 7). The main consequence of spontaneous glycation is impaired elasticity, which is essential to blood vessels. In addition, spontaneous glycation affects protein functioning. This process, also, well describes the concept of accumulation of metabolic waste that promotes aging(1).

All in all, inflammation, oxidation and glycation are biochemical processes closely related to molecular damage accumulation and aging, as pointed out by Paolo Giacomoni, PhD, in his article Ageing, science and the cosmetics industry(3). 

Therefore, Age Management Medicine, as a progressive, preventative, proactive specialty focused on health, not diseases, is expected to take action in order to delay the accumulation of damage, aiming at health maintenance. For that, it is important that Age Management practitioners act in a way to control the biomarkers of inflammation, oxidative stress and glycation. I must say that antioxidant protection may be easier to be measured in some situations than oxidative stress, including levels of antioxidant minerals, such as zinc, copper, manganese and selenium and/or antioxidant vitamins, such as vitamin C and vitamin E. Also, an anti-inflammatory, antioxidant and antiglycant diet and supplements should always be included in an anti-aging program(8, 9). 

In this article, we want to call attention to anti-inflammatory, antioxidant and antiglycant foods that may be beneficial for most people. We can’t assure for “everyone“, since 21st century medicine announces in a loud voice that “not every healthy food is healthy for you“. 

It is important to remember that what counts is the combination of foods that, in the end, promotes (or not) inflammation, oxidation and glycation. The final balance must favor anti-inflammation, antioxidation and antiglycation, but it doesn’t mean that you can not eat any pro-inflammatory food at all, such as egg yolk. However, many pro-inflammatory ones definitely should be avoided, particularly highly processed foods.

You don’t need a list of anti-inflammatory foods and another list of antioxidant ones, because most are both anti-inflammatory and antioxidant at the same time. There’s no point in making two separate lists. Some are more anti-inflammatory, some are more antioxidant, but they all work fine together. So, here it goes: a good list of “anti-inflammatory and antioxidant foods” for you – taken from my own site – including some beverages and spices:

  • Turmeric or Curcuma longa
  • Red Gold or Crocus sativus
  • Green tea or Camelia sinensis
  • Ginger or Zingiber officinale
  • Black pepper or Pipper nigrum
  • Omega-3-rich fish (such as wild salmon) and their oil
  • Omega-3-producing algae and their oil
  • Chia seeds and their oil
  • Flax seeds and their oil
  • Sesame seeds and their oil
  • Grape seeds and their oil
  • Avocado and its oil
  • Extravirgem olive oil
  • Berries (blueberry, strawberry, blackberry, raspberry, cranberry, maquiberry, acai berry, cherry, bilberry, among others)
  • Walnuts
  • Oatmeal
  • Mushrooms, such as shitake and shimeji
  • Pineapple
  • Papaya
  • Pomegranate
  • Plum
  • Prune
  • Apple
  • Acerola
  • Kiwi
  • Citric fruits, such as lemon, orange and tangerine
  • Red wine and dark grapes
  • Tomato
  • Pepper and paprika
  • Parsley
  • Cinnamon
  • Chlorella
  • Dark green leaves, such as watercress, arugula, spinach and kale
  • Broccoli
  • Celery
  • Purple cabbage
  • Purple onion
  • Eggplant
  • Carrot
  • Pumpkin
  • Sweet potato 
  • Cacao, cacao nibs and dark chocolate

As far as glycation is concerned, what you should be mainly concerned about is to have total carbohydrate (kcal) divided by total protein (kcal) ≤ 1,3 (40% carbohydrates and 30% protein from the total amount of calories per meal). Each meal is a moment of balance. So, you can’t eat a lot of carbohydrate at breakfast and a lot of protein at dinner, thinking that you are able to compensate what you have eaten in the morning. Certainly it is a good idea to avoid sugar totally, as much as high glycemic index foods and beverages, but, even so, you may have some if, in each meal, this carbo/protein rate is maintained. 

An Age Management Practitioner must check some laboratory biomarkers to see whether the patients are well protected by their dietary choices. In our context, I always include systematically in my clinical investigation: ultrasensitive C reactive protein (CRP), ferritin, levels of vitamin C, vitamin E, vitamin A, 25-OH-vitamin D, vitamin B12, homocysteine, zinc, copper, manganese, selenium, oxidised LDL, insulin and glycated hemoglobin, but others may be requested, such as glycated albumin, ceruloplasmine and holotranscobalamin.

Also, there’s an interesting test to measure cellular inflammation, that is, the rate between arachidonic acid (ARA) and eicosapentaenoic acid (EPA)(10, 11), which ideally should be between 1,5 and 3*. All these tests help an Age Management Practitioner to manage the patient’s inflammation, oxidation and glycation damage accumulation and prepare them to give good advice about which choices to make to maintain a healthy diet – a very important step for those focused on maintaining health, as proposed by Age Management Medicine.

References:

  1. Sergiev, P. V., Dontsova, O. A., & Berezkin, G. V. (2015). Theories of aging: an ever-evolving field. Acta naturae, 7(1), 9–18.
  2. Giacomoni, P.U., & Rein, G. (2004). A mechanistic model for the aging of human skin. Micron, 35 3, 179-84 .
  3. Giacomoni P. Ageing, science and the cosmetics industry. EMBO Rep 2005; 6: 45-48.
  4. Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE (2000) Inflammatory mechanisms in Alzheimer’s disease: inhibition of β- amyloid-stimulated proinflammatory responses and neurotoxicity by PPARγ agonists. J Neurosci 20: 558–567. 
  5. McGeer EG, McGeer PL (1998) The importance of inflammatory mechanisms in Alzheimer disease. Exp Gerontol 33: 371–378 
  6. Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014). Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release. Physiological Reviews, 94(3), 909–950.
  7. Singh, R., Barden, A., Mori, T., & Beilin, L. (2001). Advanced glycation end-products: A review. Diabetologia, 44, 129–146.
  8. Ricker, M. A., & Haas, W. C. (2017). Anti-inflammatory diet in clinical practice: A review. Nutrition in Clinical Practice, 32, 318–325.
  9. Martínez-González, M., Salas-Salvadó, J., Estruch, R., Corella, D., Fitó, M., & Ros, E. (2015). Benefits of the Mediterranean diet: insights rrom the PREDIMED study. Progress in Cardiovascular Diseases, 58.
  10. Davinelli, S., Corbi, G., Righetti, S., Casiraghi, E., Chiappero, F., Martegani, S., Scapagnini, G. (2019). Relationship Between Distance Run Per Week, Omega-3 Index, and Arachidonic Acid (AA)/Eicosapentaenoic Acid (EPA) Ratio: An Observational Retrospective Study in Non-elite Runners  . Frontiers in Physiology  , Vol. 10, p. 487.
  11. Rizzo, A. M., Montorfano, G., Negroni, M., Adorni, L., Berselli, P., Corsetto, P., Berra, B. (2010). A rapid method for determining arachidonic:eicosapentaenoic acid ratios in whole blood lipids: correlation with erythrocyte membrane ratios and validation in a large Italian population of various ages and pathologies. Lipids in Health and Disease, 9(1), 7.

Isabela M. B. David, M.D. is a Clinical Nutrition Practitioner in the Post-Graduate Program in Health Sciences, Universidade do Sul de Santa Catarina. Av. Pedra Branca, 25. Palhoça SC, 88137-270, Brazil. (2017)  Contact: contato.isabeladavid@gmail.com

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