Aging Mechanisms PDF

Popławski Tomasz Aging Cell 2013 153, 1194-1217 Cell 2013 153, 1194-1217 2  https://doi.org/10.1016/S0065-2423(01)35014-X Comparison of the percentage of people living at various ages and periods of time with the "ideal" maximum life span: A, "ideal"; B, 1980...

Popławski Tomasz Aging Cell 2013 153, 1194-1217 Cell 2013 153, 1194-1217 2  https://doi.org/10.1016/S0065-2423(01)35014-X Comparison of the percentage of people living at various ages and periods of time with the "ideal" maximum life span: A, "ideal"; B, 1980; C, 1920; D, 1900; E, 2000 Bc 3 National Vital Statistics Reports (2008) 57, vol. 1. 4  Aging and longevity are controlled via the complex and largely cryptic interplay between random and deterministic factors that include genetic programming, environmental stresses, lifestyle, cellular countdown clocks, and molecular repair processes. 5 6 Wear and tear theories of aging hypothesize that the changes associated with old age and death itself reflect the accumulation of damage over time 7 8 9  the ester bonds that bind fatty acids to their cognate glycerolipids  the glucosidic bonds that link the monosaccharide units of carbohydrates  the phosphodiester bonds that hold polynucleotides together and link the head groups of phospholipids to their diacylglycerol partners 10 11 12 https://doi.org/10.1002/mus.880090109 13 http://dx.doi.org/10.1155/2012/217037 14 http://dx.doi.org/10.1007/978-3-540-38502-8_3 15 16 https://doi.org/10.3389/fcell.2020.575645 17 The efficient production of ATP is essential to cell vitality. Mitochondria play a central role in apoptosis, programmed cell death. Mitochondria lack the capacity to repair damage to their DNA. https://doi.org/10.1038/s41580-019-0173-8 18 19 20 21 http://dx.doi.org/10.1016/j.molmet.2013.11.006 22 23 24 25 Adapted from Kierdof et al. (2013) 26 27 10.1007/s10522-019-09808-3 28 29 https://doi.org/10.1016/j.bbadis.2019.01.006 30 31 32 33 34 35 36 37  Advanced glycation end products are potentially harmful and heterogeneous molecules derived from nonenzymatic glycation.  The pathological implications of AGEs are ascribed to their ability to promote oxidative stress, inflammation, and apoptosis.  AGEs are important in the development and progression of various aging-related pathological conditions, such as diabetes, cardiovascular complications, gut microbiome-associated illnesses, liver or neurodegenerative diseases, and cancer 38 39 40 DNA repair The Integrity of DNA Is Maintained by Proofreading & Repair Mechanisms Mutations resulting from errors caused by missing or chemically modified nucleotide bases can be particularly harmful, as they may result in oncogenic transformation or render a cell vulnerable to further damage. 41 The somatic mutation theory of aging 42 the changes we see as the body grows older are driven by the gradual accumulation of small mutations in the DNA of healthy cells  healthy cells could tolerate so many mutations 43 Formation of an isoaspartyl linkage in a polypeptide backbone and its repair via the intervention of isoaspartyl methyltransferase. 44 45 46 Lifespan Versus Body Mass for Several Mammals 47 48 49 https://doi.org/10.3389/fgene.2020.630186 50 In eukaryotic cells, long repeating sequences called telomeres cap the ends of their linear chromosomes. These telomeres progressively shorten each time a somatic cell divides. When a somatic cell’s telomeres become too short, it enters replicative senescence. Thus, telomeres are hypothesized to serve as a countdown clock for somatic cells. 51 52 Animal lifespan may be genetically programmed. Mutation of the daf-2 gene in Caenorhabditis elegans yielded worms whose lifespan was 70% longer than wild type. 53