Theories of Biological Aging: Role of Oxidative Stress


Karasu C.

TURKIYE KLINIKLERI TIP BILIMLERI DERGISI, cilt.28, sa.6, 2008 (SCI İndekslerine Giren Dergi) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 28 Konu: 6
  • Basım Tarihi: 2008
  • Dergi Adı: TURKIYE KLINIKLERI TIP BILIMLERI DERGISI

Özet

Aging is a complex process that is manifested within an organism at genetic, molecular, cellular, organ, and system levels. Two principal types of aging theories have been developed: Theories of "accidental" aging produced by "errors" represented by random deleterious mechanisms that induce progressive damage of various levels; and theories of "programmed" aging induced by the collection of by products of gene action selected to increase reproductive fitness. The oxidative hypothesis of senescence (free radical theory of aging), since its origin in 1956 by Denham Harman, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. These two principle types of aging theories are not mutually exclusive, especially when oxidative stress is considered. Many features of aging result from the incapacity of cells to adapt to stress conditions leading to genomic instability. When damage of macromolecules accumulates irreversibly, mitotic cells from renewable tissues rely on either of two mechanisms to avoid replication. They can permanently arrest the cell cycle (cellular senescence) or trigger cell death programs. Evidence suggests that cellular senescence acts as an in vivo tumor suppression mechanism by limiting aberrant proliferation. It has also been postulated that cellular senescence contribute to the physiological processes of normal organismal aging. Recent data have demonstrated the in vivo accumulation of senescent cells with advancing age. Some characteristics of senescent cells, such as the ability to modify their extracellular environment, could play a role in aging and age-related pathology.