Friday, October 20, 2017

Healthy Aging: Protein Consumption Advice for the Elderly

Figure 1.  Based on a survey of over 1500 people of 65 and over in the UK (source: @SilverM00NSHOTS)


Figure 2.  Rockwood frailty index[59]



Protein is essential for your health. In the Mitochondrial Metabolic Therapy diet, Dr Mercola recommends you to target maximum 45 to 55 grams of protein per day for the optimal health. Why?

The reason is: when you consume more protein than your body needs, it may have the following adverse health effects:
  • Excess protein burdens kidneys with removing extra nitrogen waste products from your blood[15]
  • Excess protein stimulates the production of IGF-1 (Insulin-like growth factor one)
    • The more IGF-1 you have in your bloodstream, the higher your risk for developing cancers, such as prostate cancer[45]
  • Excess protein stimulates mTOR
    • More details in this article
However, do consider to increase protein intake when
  • The older you get (e.g., over 65 years old) the more important protein intake becomes to avoid lean muscle loss.[12]
    • Chan et al.[54] reported that total and animal protein intakes were not associated with changes in physical performance and appendicular skeletal muscle (ASM) over a 4-year follow-up in Chinese community-dwelling older adults. However, people who had a relative vegetal protein consumption higher than 0.72 g/kg BW/day (Body Weight per day) lost significantly less ASM during the follow-up.
    • However, studies found that muscle protein synthesis (MPS) reached a plateau at ~30 g of protein intake per meal.[52,53] 
      • According to Symons et al., meals providing large amounts of protein (e.g., 90 g) have no greater effects on MPS than moderate meal servings (e.g., ~30 g of protein).[53]
      • Hence, researchers suggested that a spread feeding pattern with at least 30 g of dietary protein during the main meals (i.e., breakfast, lunch, and dinner) could be a more effective strategy
    • If we are going to increase our protein consumption after age 65, it would preferably be plant-based proteins to protect us from frailty[48]
      • If you choose plant-based proteins, note that the importance of co-ingestion of protein from foods such as soy, bean, and nuts, which could provide the quantity of EAAs (essential amino acids), BCAAs (branched EAAs), and leucine required for stimulating MPS, reducing the risk of sarcopenia and, thus, frailty.
  • On days when you are seeking to increase your muscle mass with strength training
In this article, we will focus on the protein's role played in regulating mTOR's activities.

Video 1.  Starving Cancer with Methionine Restriction (YouTube link)

Figure 3.  The mTOR Pathway in the control of protein synthesis


What's mTOR


mTOR (a kinase) was named as it is the mammalian Target Of Rapamycin which is an antibiotic and immune-suppressor drug that inhibits mTOR's activities. It plays a key role in the regulation of protein synthesis , cell proliferation and autophagy.[10,20] 
The process of clearing spent or defective proteins from cells, known as autophagy, slows down in people over the age of 65.  New UC Riverside research points to cells’ slowing ability to clean themselves as the likely cause of unhealthy brain buildup (i.e., amyloid plaques and neurofibrillary tangles).[61] 

Autophagy can be induced by fasting. When cells run short on proteins from an individual’s diet, they fill the void by recycling proteins already present in cells. Exercise also increases autophagy.  


mTOR forms two multi-protein complexes known as complex 1 (mTORC1) and 2 (mTORC2). Raptor and Rictor are the core proteins for mTORC1 and mTORC2, respectively.

In this article, we will use mTOR in general and mTORC1 in specific, but interchangeably, in the discussion of aging and carcinogenesis. Note that our understanding of the role of mTORC2 in the wider pathway is still evolving and will not be covered here.

Figure 4.  Leucine is predominantly found in animal-based food.

Figure 5.  Methionine is predominantly found in animal-based food.

Regulation of Protein Synthesis


In order for cells to grow and proliferate (i.e., manufacturing more proteins), the cells must ensure that they have the resources available for protein production. For example, cells must have
  • Adequate energy resources
    • An adequate energy intake is normally reached through the consumption of fat and carbohydrate.
  • Availability of amino acid nutrients
  • Oxygen abundance
  • Proper growth factors
in order for mRNA translation to begin (i.e., protein production).

mTORC1 is known to regulate protein synthesis in the following ways:
  • When mTOR is stimulated
    • It cues the cell to grow and proliferate
    • If over-activated,
      • mTOR signaling significantly contributes to the initiation and development of tumors
      • Hence come the benefits of
        • Methionine restriction diets[21,23,27,32,38,41]
        • Leucine restriction diets (video) [10,17,37]
    • When mTOR is limited
      • It instructs the cell to turn on the array of repair and maintenance processes at its disposal, including autophagy (cleaning up cellular debris), DNA repair, and activating intracellular antioxidants.
        • Autophagy and mitophagy, which are largely controlled by the mTOR, play an important role in controlling the amount of inflammation in your body and help slow down the aging process
      • Rapamycin inhibits mTORC1, and this appears to provide most of the beneficial effects of the drug
      • Plant-based diets (a better alternative) are associated with lower risk for many cancers because their capability of “down-regulation” of mTOR.
    Figure 6.  Milk-mediated mTORC1 signaling[60]

      mTOR and Cancer


      There is a growing body of evidence that mTORC1 is upregulated in many types of cancers and plays a role in carcinogenesis[18,19,60]
      Milk consumption during adult life is associated with higher risks of common mTORC1-driven cancers, including Prostate Cancer, Breast Cancer, hepatocellular carcinoma, diffuse large B-cell lymphoma, and promotes the neurodegenerative diseases, Parkinson’s disease and Alzheimer disease, which are all related to overstimulated mTORC1 signaling.[60]

      Below we will discuss the relationship of mTOR and two specific cancers:

         Prostate Cancer
        • When mTOR is stimulated
          • mTORC1 is upregulated in nearly 100% of advanced human prostate cancers.[7]
        • When mTOR is limited
          • The potential prostate cancer protective effect of a plant-based diet may be explained by the reduction of dairy- and animal meat-derived leucine intake, and especially lower insulin and IGF-1 signaling of non-dairy plant-based diets attenuating overall mTORC1 activity.[10]

        Breast Cancer
        • When mTOR is stimulated 
          • Higher mTOR expression has been noted in breast cancer tumors, and associated with more aggressive disease, and lower survival rate among breast cancer patients.[8]
        • When mTOR is limited 
          • Compared with the Swedish general population, women hospitalized for anorexia nervosa—one marker of caloric restriction—prior to age 40 years had a 53% lower incidence of breast cancer; nulliparous women with anorexia nervosa had a 23% lower incidence, and parous women with anorexia nervosa had a 76% lower incidence.[9]

        Video 2.  Prevent Cancer From Going on TOR (YouTube link)

        How to Age Gracefully?


        Life has one imperative which is to reproduce. Once our reproductive peak has passed, nature becomes apathetic to our survival, and we commence the process of programmed degeneration we call aging. To age gracefully, the goal is to
        • Delay aging while simultaneously switch on restorative pathways — activate our internal housecleaning mechanisms (i.e., autophagy).
        As a child, milk is presented as an endocrine signaling system, which activates mTORC1 —promotes cell growth and proliferation. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of human.

        However, as we start aging, we should tip the balance of growth  towards more on the restorative pathways. As an adult, if you still persistently abuse the growth-promoting signaling system of cow milk. The consequences of sustained proliferative signaling is what we have witnessed today—the rising of cancer in the developed countries.

        On the other hand, plant-based diets, especially cruciferous vegetables, not only decrease leucine-dependent mTORC1 activation but also they provide natural plant-derived inhibitors of mTORC1. Increasing studies have demonstrated that
        • 3,3'-Diindolylmethane (DIM)
        • Epigallocatechin gallate (EGCG)
        • Genistein
        • Curcumin
        • Resveratrol
        • Caffeine
        all inhibit mTORC1 signaling directly or indirectly and have been suggested to reduce the risk of prostate cancers and other common cancers.

        Finally, to age gracefully, we should consider:

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