How to Avoid the Garbage Catastrophe of Aging

P.D. Mangum writes about The Garbage Catastrophe of Aging and How to Avoid It.

The main mechanism for damage repair is autophagy, from the Greek for “self-eating”. Autophagy is the cellular self-cleansing process in which cellular organelles such as mitochondria and proteins within the cell are broken down and their components recycled for making new organelles and proteins.

Autophagy is a daily occurrence — or should be — with peaks and troughs of activity. The absence of food strongly increases the rate of autophagy, so that in young organisms at least, its rate rises dramatically overnight. Fasting even longer than overnight further increases the rate of autophagy.

Other interventions besides fasting also increase autophagy, for instance, exercise and certain drugs and supplements.

But in older organisms, the capacity for increasing autophagy in response to fasting or other stimuli decreases. This leads to a rising level of damage that interferes with cell function and is characteristic of aging.

Autophagy is crucial for the organism. Treatments that prolong lifespan, for example calorie restriction, fasting, or even genetic manipulation of insulin signaling, require the organism to possess an intact autophagy mechanism to work.
No autophagy, no lifespan extension.

How to prevent and/or slow aging
Iron
I’ve argued that iron is the primary driver of aging, and looking at aging from the standpoint of the garbage catastrophe lends new support to this idea. Why?

Because iron is required for the formation of lipofuscin, the cell’s toxic waste.

Therefore, to slow the formation of lipofuscin, keep iron levels in the low normal range. Ferritin is the body’s main iron-storage molecule, and the more you have of it, the more will be turned over on lysosomes and the more iron will be left there, creating lipofuscin and catalyzing chemical reactions that damage cell structures.

Intermittent fasting
Intermittent fasting (and calorie restriction, which few people are willing to do over the long term) activates autophagy potently. Therefore fasting increases the clearance of damage. In older people, whose cells are clogged with garbage that inhibits autophagy, fasting may bring the rate of autophagy back to youthful levels.

Autophagy boosters
Certain substances/drugs can boost autophagy. These include resveratrol, hydroxycitrate, curcumin.

Exercise
Exercise increases autophagy and thus the clearance of cellular damage.

Normal blood sugar
Keeping blood sugar in the low normal range will help to prevent the formation of advanced glycation end-products (AGE), one of the constituents of non-degradable cellular garbage.

Experimental treatments
There have been a few reports of substances that can clear lipofuscin from cells. If these were to pan out, they could turn out to be potent anti-aging interventions.

One such substance is a form of cyclodextrin, which is a cheap safe molecule that is already used as an excipient in medicines.10

This form of cyclodextrin upregulates autophagy and clears cellular junk.

Read more here.

There is no such thing as healthy aging

P.D, Mangan writes at roguehealthandfitness.com,

The four pathologies of aging

Aging can be defined as a breakdown of homeostasis; that is, the organism as it gets older finds it increasingly difficult to regulate itself and to maintain all systems in a state of balance and of health.

A more practical way of defining aging is as increasing susceptibility to disease. Aging is the prime factor in disease risk.

There are four main cellular derangements of aging: increased inflammation, increased oxidative stress, increased mitochondrial dysfunction, and lower levels of autophagy. They are all related and linked through cellular sensors and pathways, most notably through the cellular energy sensor AMPK, which regulates aging. Improving the parameters of one of these factors also improves the others. Lowering oxidative stress, for example, also entails lower levels of inflammation and better mitochondrial function.
Autophagy

Autophagy, from the Greek for “self-eating”, is the regulated process through which the cell breaks down parts of itself and by sequestering them into vacuoles and digesting them. Those parts that are broken down are mainly organelles and proteins that have passed their expiration dates. In this way, autophagy provides for a continuous process of self-renewal by breaking down older structures, allowing for new ones to be built in their place.

One characteristic of aging is the accumulation of damage, and this is largely due to the failure of autophagy to attain normal functional levels. From this statement, it can be seen that bringing levels of autophagy to youthful levels can ameliorate aging by clearing out damaged parts of the cell.

There is no such thing as healthy aging. Aging means increasing susceptibility to disease and the breakdown of the organism. Being healthy when older requires retarding the aging process.)

Before we get to ways to increase autophagy, how can you completely screw up the process and ensure that your autophagy levels decline and that you get old and unhealthy in a hurry? First of all, eat all the time: graze, eat snacks, never let your body out of the fed state. Second, be sedentary and gain weight. Doing this increases levels of inflammation and oxidative stress and causes a decline in autophagy. Third, make sure all your food is processed and that you never eat a vegetable.

1.Exercise induces autophagy in peripheral tissues and in the brain.

2. Fasting: Autophagy is “a process that is potently triggered by fasting.”

3. Chemical autophagy boosters: See my article “Intermittent Fasting Boosters / Autophagy Enhancers”. These chemical autophagy boosters include resveratrol, hydroxycitrate, nicotinamide, curcumin, lithium, and EGCG (from green tea). These are all readily available over-the-counter, and are cheap and safe.

Insulin signaling from food could override the autophagy-boosting effects of these supplements, so take them during the fasted state.

4. Ketosis. Ketosis results from relatively prolonged abstention from dietary carbohydrates. It stimulates autophagy (JBC) and promotes autophagy in the brain (Medical Hypotheses), which is likely important to the neuroprotective effects of the ketogenic diet.

Please read more here.