By @Entropy


By @Entropy

Summary This chapter describes the possible mechanisms underpinning the concept extending longevity. It discusses why reducing calorie intake reduce free radicals leading to life extension.

Chapter 1

Calorie restriction Aging

Free Radical Build up: Oxidative Stress

Oxidative stress is the disparity between free radical build up and the ability of the body to eliminate or detoxify their deleterious effects by antioxidants. Oxidative stress accelerates aging. Studies show that the lower the metabolic rate, the greater the lifespan. Conversely, the higher the metabolic rate, the greater the oxygen consumption the greater the oxidative stress, the shorter the lifespan. In other words, high concentrations of free radicals (ROS) reduces life expectancy. The corollary also supports these findings: namely, reduction of oxidative stress slows aging thus extending longevity. According to lab findings, calorie restriction (CR) reduces excessive accumulation of free radicals in various species and increases longevity. It is well established that energy consumed by aerobic metabolism leads to ROS formation. About 3.5% of consumed oxygen is converted to ROS. These include the superoxide radical (O2•−), hydrogen peroxide, and the hydroxyl radical (OH•). It follows then that to increase life span, oxygen consumption must be decreased. One way this feat may be achieved is through CR. The traditional Okinawan diet is calorie restricted. Evidence indicates that residents of Okinawa live longer than anywhere else in the world. Okinawan centenarians have a lower level of lipid damage by peroxidation compared to their septuagenarian peers, which indicates less free radical attack. Furthermore, Okinawans live on a strict CR diet. They adhere to the 80% rule: they stop eating when they feel 80% full. It is referred to as hara hachi bu.

CR reduces protein oxidation which changes the physical and chemical properties of proteins, including structure, solubility and enzyme activities. It is also involved in pathological conditions. They include respiratory diseases and parasitic infections Studies indicate that protein oxidation is critical to the regulation of reproduction, nutrition, metabolism, lactation, gut health and neonatal physiology.[1]

Protein oxidation is a reflection of cellular damage, aging and age-related disorders. Studies on obese human subjects showed that after 4-weeks on a calorie restricted (CR) diet protein oxidation was markedly reduced. Excess ROS can be offset by oxygen scavenging. To slow aging, it is necessary to both decrease ROS production and increase ROS removal. Genetically altered animals with an abundance of the antioxidant enzymes – superoxide dismutase and catalase – have a 30% extension of lifespan. In effect, this means that the greater the capacity of the organism to remove free radicals, the longer the lifespan.[2],[3]

Peroxidation: free radicals attack of lipids

Peroxidation is an oxidation process by free radicals that results in the formation of a peroxide end product. Generated free radicals (ROS) attack membrane lipids thereby compromising the integrity of the cell membranes.[4] Products of peroxidation, including isoprostanes, circulate in blood plasma and are excreted in urine. They are also bio-markers of oxidative stress.[5] Urinary isoprostanes are higher in the elderly, alcohol consumers and those afflicted with Alzheimer’s disease and chronic obstructive pulmonary disease. Along with their metabolites, isoprostanes are elevated in the urine of cigarette smokers. Furthermore, urinary isoprostanes were higher in obese women with a higher calorie intake compared with non-obese controls and were significantly lowered through weight loss. 

Free radicals attack DNA giving rise to chemically corrupted sites on the DNA. These modified sites cause mutations and cell death. They are also linked to mutagenesis, carcinogenesis and neurologic disorders. A reliable indicator of DNA damage by free radical attack is the presence of 8-oxoG.[6] The formation of both 8-oxoG and modified DNA bases increase with age. Moreover, the greater the amount oxygen consumed the greater the oxidative damage to the DNA. Therefore, DNA damage from ROS produced by high energy consumption is a potential cause of accelerated aging.[7] Accordingly, calorie restriction reduces energy usage and thus prolongs life.[8]


[1] Pietro Celi and Gianfranco Gabai. 2015. Oxidant/antioxidant balance in animal nutrition and health: the role of protein oxidation. Front. Vet. Sci. 26 October.

[2] Antioxidant enzymes: They include the superoxide dismutase (SODs), catalases and glutathione peroxidases (GPXs). They are involved in the catalytic conversion of ROS and their by-products into stable molecules. They form a protective mechanism against cell damage.

[3] July 26 2020

[4] Lipid peroxidation: oxidative damage of cellular membranes, lipoproteins, other lipids including unsaturated fatty acids. It is a chain reaction created by free radicals.

[5] Isoprostanes: These are like prostaglandins and are formed by peroxidation of essential fatty acids (primarily arachidonic acid). 8-iso–prostaglandin F2α is an indicator of oxidative stress.

[6] 8-oxoG: a common DNA lesions caused by ROS modification of the guanine base. It leads to mismatched pairing.

[7] [7] Leonie K Heilbronn, Eric Ravussin. 2003. The American Journal of Clinical Nutrition, 78 (3), Pages 361–369, 

[8] Indar Maharaj. 2018. The Eloquence of Effort: Beware the Path of Least Resistance.

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