Rapid increase in human life expectancy: will it soon be limited by the aging of elastin?

Abstract

The postponement of the most frequent age-related diseases stimulated speculations of the possibility of "dying of old age". The selective decline of individual physiological functions-aging in spare-parts-indicates however the potential limitation of the life-span by the rapid decline of some of the vital parameters. We explored a possibility of such a limitation of maximal life-span by the age-related alteration of elastin, consisting in Ca-accumulation, lipid deposition and elastolytic degradation. The quantitative evaluation of these processes suggests an approximative upper limit for the elastic properties of the cardio-respiratory system of about 100-120 years, at least, as far as elastin is involved. This process, age-related alterations of elastic fibers, is however not the only one limiting the functional value of the cardiovascular system. Crosslinking of collagen fibers by advanced glycation end-products certainly contributes also to the age-dependent rigidification of the cardiovascular system. Therefore the answer to the initial question, can age-dependent alterations of a single matrix macromolecule be limiting such vital functions as the cardio-respiratory system-is a cautious yes, with however the caveat that other, independent mechanisms, such as the Maillard reaction, can also interfere with and limit further the functional value of such vital physiological functions.

Tissue elasticity and the ageing elastic fibre

“…Although up-regulation of ECM protease expression is a unifying feature of age-related inflammatory conditions such as emphysema (Robbesom et al 2008), atherosclerosis (Robert et al 2008) and UVinduced photoageing (Fisher et al 1996), the constitutive expression of MMPs in non-inflamed lung, aorta and skin (Chen et al 2005;McNulty et al 2005;Meyer et al 1998) may be sufficient, given the longevity of ECM assemblies, to gradually degrade proteins over many years. To date, eight MMPs have been shown to degrade elastic fibre proteins in vitro: insoluble elastin is degraded to soluble fragments by MMP-2, -7, -9, -10, -12 and -14 (Chakraborti et al 2003;Taddese et al 2008), whilst fibrillin microfibrils and peptides are catabolised by MMP-2,-3,-9,-12 and -13 (Ashworth et al 1999;Tsuruga et al 2007).…”

“…In addition to these major degradative mechanisms, the structure of elastic fibres in ageing tissues may also be altered by calcification, aspartic acid racemization, lipid accumulation and mechanical fatigue (Bailey 2001;O'Rourke and Hashimoto 2007;Robert et al 2008). Calcium accumulates in ageing blood vessel walls and is strongly bound to the micro-fibrillar component of elastic fibres (Robert et al 2008).…”

“…Calcium accumulates in ageing blood vessel walls and is strongly bound to the micro-fibrillar component of elastic fibres (Robert et al 2008). In vitro studies have demonstrated that microfibrillar structure is highly sensitive to the concentration of calcium in the local environment (Wess et al 1998).…”

“…In vitro studies have demonstrated that microfibrillar structure is highly sensitive to the concentration of calcium in the local environment (Wess et al 1998). This bound calcium may also play a role in mediating the uptake of lipids by elastic fibres in the ageing arterial wall (for a review see Robert et al 2008). In addition to binding extracellular ions and biomolecules, L-forms of aspartic acid within elastic fibre proteins spontaneously convert to D-forms at a predictable rate (Shapiro et al 1991).…”

“…Elastic fibrerich dynamic tissues are therefore able to deform and store energy under normal physiological loads and to use this energy to drive recoil back to a resting state (Gosline et al 2002). The maintenance of these mechanical properties is central to the function of dynamic tissues within the cardio-respiratory system and it has been suggested that the age-related failure of elastic fibres may underpin the apparent 100-to 120-year limit on human life expectancy (Robert et al 2008) Although much progress has been made in recent years in defining elastic fibre composition, many questions remain as to the precise macro-molecular structure of fibrillin microfibrils and the functional roles played by distinct elastic fibre components in both mediating tissue elasticity and maintaining tissue homeostasis. This review considers how age-related The major elastic fibre components: elastin (a) and fibrillin microfibrils (b).…”