A combo of two theories explain aging.
1. Oxidative damage.
2. Impaired proteostasis.
How can "aging" be measured?
1. Methylation of genes accumulate signifying genes are epigenically turned off.
2. Percentage or accumulation of senescent cells signifying survival without quality control mechanisms such as proteostasis. A subset of these senescent growth arrested cells become cancer or contribute to neurodegenerative changes.
What proof is known?
1. Cell, tissue and organ function is inversely related to methylation counts or "biological age."
2. Cell penetrating protein that kills senescent cells allows stem cells to replace the non functioning cell with a fully functioning and non toxic cell.
Senescent cells arise when pro oxidant forces exceed antioxidant and proteostasis forces.
Proteostasis is impaired by clock gene reduction of spermidine synthesis and reduction of dietary Spermidine supplements.
Antioxidant forces are reduced by methylation of ARE antioxidant response element gene due to pro oxidation forces.
Therefore, accumulation of senescent cells and abnormal protein aggregates in cells indicate inadequate autophagy, proteostasis.
What is the solution to biological AND chronological aging?
Hydrogen rich water, sulforaphane, melatonin and wheat germ/spermidine that activate Nrf2 that stimulates ARE and increases protective antioxidant capacity and restores proteostasis/autophagy.
Cell, tissue, organ and organism quality control is restored and aging slowed down until agents that promote senescent cells to die via apoptosis can restore a young phenotype is available.
Happily (n)ever after: Aging in the context of oxidative stress, proteostasis loss and cellular senescence
Aging is a complex phenomenon and its impact is becoming more relevant due to the rising life expectancy and because aging itself is the basis for the development of age-related diseases such as cancer, neurodegenerative diseases and type 2 diabetes. Recent years of scientific research have brought up different theories that attempt to explain the aging process. So far, there is no single theory that fully explains all facets of aging. The damage accumulation theory is one of the most accepted theories due to the large body of evidence found over the years. Damage accumulation is thought to be driven, among others, by oxidative stress. This condition results in an excess attack of oxidants on biomolecules, which lead to damage accumulation over time and contribute to the functional involution of cells, tissues and organisms. If oxidative stress persists, cellular senescence is a likely outcome and an important hallmark of aging. Therefore, it becomes crucial to understand how senescent cells function and how they contribute to the aging process. This review will cover cellular senescence features related to the protein pool such as morphological and molecular hallmarks, how oxidative stress promotes protein modifications, how senescent cells cope with them by proteostasis mechanisms, including antioxidant enzymes and proteolytic systems. We will also highlight the nutritional status of senescent cells and aged organisms (including human clinical studies) by exploring trace elements and micronutrients and on their importance to develop strategies that might increase both, life and health span and postpone aging onset.
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