http://www.krisverburgh.com/nutrigerontology.html
Kostens sammensætning af de tre makronæringsstoffer protein, kulhydrat og fedt er ikke ligegyldig for aldring ifølge Kris Verburgh. Det argumenteres at de to makronæringsstoffer kulhydrat og protein hhv. kan (over)stimulere en Insulin/IGF-1 pathway og en mTOR (mamalian Target of Rapamycin) pathway i pattedyr, hvormed kroppens forfald fremskyndes. De to kostfølsomme 'aging pathways' kan man sætte ud af spil i laboratorieforsøg med bla. rotter som lever længere, og hos mennesker kender man til omstændigheder hvor disse to pathways af en eller anden grund er sat ud af spil, se min fremhævning:
A mounting body of research shows that loss of function of the IIS pathway and mTOR pathway increases lifespan. Modulating these pathways, genetically or nutritionally, can impact the rate of aging and postpones the advent of aging-related diseases.
For example, mice with a fat-specific insulin receptor knockout (FIRKO) genotype live 18% longer (Blüher et al., 2003) and reducing insulin receptor signaling in the mouse brain extended lifespan up to 18% (Taguchi et al., 2007). Homozygous deletion of the insulin receptor substrate 1 (Irs1-/-), an effector of the insulin receptor, increased median lifespan by 32% in female mice. However, deletion of IRS-1 in male mice did not lead to an increased lifespan (Selman et al., 2008). Mice heterozygous for the IGF-1 receptor (Igf1r+/-) live on average 26% longer than their wild-type littermates (Holzenberger et al., 2003). In humans, the insulin/insulin-like growth factor signaling pathway also is involved in lifespan regulation. Polymorphic variants of IGF-related pathways confer health and lifespan benefits in humans (Bonafè et al.,2003; Kojima et al., 2004; Pawlikowska et al., 2009). Female Ashkenazi Jewish centenarians show an overrepresentation of loss-of-function mutations in the IGF-1 receptor (Suh et al., 2008). Laron dwarves, who are growth hormone receptor deficient, have reduced levels of IGF-1, and despite being generally overweight, they have a major reduction in the risk of type 2 diabetes and cancer (Guevara-Aguirre et al., 2011; Steuerman et al., 2011). People with acromegaly (due to increased growth hormone and IGF-1 production) have a two- to threefold increase in mortality, mostly because of vascular disease (Clayton, 2003).
The IIS and mTOR pathways in aging-related disease
How do the IIS and mTOR pathway contribute to the aging phenotype? A continuous stimulation of the IIS and mTOR pathways leads to a higher risk of aging-related diseases and reduced lifespan via reduced autophagy (less clearance of protein aggregates and cellular organelles), increased protein agglomeration and proteotoxicity (mTOR activation leads to increased protein production and reduced protein clearance), inflammation, reduced expression of antioxidant proteins, mitochondrial dysfunction, and other mechanisms (Kenyon, 2010; Fontana et al., 2010; Johnson et al., 2013; Cuervo, 2008). These mechanisms increase the risk of insulin resistance (Shah et al., 2004), atherosclerosis (Martinet et al., 2014), cardiomyopathy (Willis & Patterson, 2013), neurodegenerative diseases (O'Neill et al., 2012, 2013), cancer (Martini et al., 2014), osteoporosis (Glantschnig et al., 2003) and other aging-related diseases and symptoms.
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