At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

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Free Radicals in the Physiological Control of Cell Function

Living in an oxygenated environment has required the evolution of effective cellular strategies to detect and detoxify metabolites of molecular oxygen known as reactive oxygen species. Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span.

Oxidants, oxidative stress and the biology of ageing.

Beckman, Kenneth B., and Bruce N. Ames. The Free Radical Theory of Aging Matures. Physiol. Rev. 78: 547–581, 1998. — The free radical theory of aging, conceived in 1956, has turned 40 and is rapidl...

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The Free Radical Theory of Aging Matures

Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.

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Accelerated telomere shortening in response to life stress

Oxidative stress shortens telomeres

Mild Hyperoxia Shortens Telomeres and Inhibits Proliferation of Fibroblasts: A Model for Senescence?

Lipofuscin accumulates in postmitotic cells. In human fibroblasts, accumulation of lipoftiscin as measured by cellular autofluorescence is exponential at first, but stops at a certain level. At the same time, cell death starts to decrease cell numbers significantly. Artificial lipofuscin-like material can be prepared by UV-crosslinking of mitochondria] preparations. This material is easily phagocytosed by human fibroblasts and results in an increased cellular lipofuscin accumulation. Such a forced lipofuscin accumulation is sufficient to block cellullar proliferation within a short time and to induce cell death as soon as the cellular lipofuscin autofluorescence reaches the same upper limit as that observed in senescent cells. It is concluded that accumulation of lipofuscin in postmitotic cells is not just an innocent consequence of ageing, but rather one amongst the important causes of senescence.

W.D. Döcke

Papers

Mild Hyperoxia Shortens Telomeres and Inhibits Proliferation of Fibroblasts: A Model for Senescence?

Lipofuscin accumulation and ageing of fibroblasts.