老化理論簡述

台灣將在2026年邁入超高齡社會。考慮長者個別健康及財務條件，長期照顧將是社會面臨的重大議題。至今我們對老化生物學方面仍未完全瞭解。本文分別從演化生物學的老化理論及老化生理進程理論等進展簡論老化的「為何」及「如何」。從演化角度來看，老化是由於維持長久生理功能的壓力隨時間下降所引起，進而在生命後期突變累積導致負面影響，此構成突變累積假說之基礎概念。而如突變在生命早期對個體適應性有利，但在晚期有害，就符合拮抗多效性假說。在可棄軀體假說裡，則考慮在繁衍後代與維持生命間的取捨。這些演化理論彼此間並不互相排斥，並得到群體遺傳學研究的支持。針對老化進程提出了兩大類理論：在程序老化理論中，老化是依循遺傳程序引導的生物時間表進行。在損害（或錯誤）理論中，環境的衝擊造成生理損害累積，最終導致功能喪失進而老化。而老化生理進程理論較少有定論。最近在瞭解細胞老化途徑或衰老方面的研究獲得重大進展，我們還簡要描述自由基（氧化壓力）假說。這些成果可讓我們對老化進程有更進一步的瞭解。

關鍵字

老化；演化生物；生理老化；自由基

並列摘要

Taiwan will be a super-aged society by 2026. The demand for long-term care in conjunction with the wide variation in the physical and financial conditions of the individual elderly result in a very serious societal problem. Especially since we have yet to fully understand the biological aspects of aging. Thus, we briefly discuss the 'whys' and 'hows' of aging in terms of theories developed in evolutionary biology and physiological processes for aging; respectively. Aging arises as a result of a declining pressure to maintain long-lasting physiological functions, thus allowing the accumulation of mutations that exert negative effects during late stages of life. This forms the basis for the Mutation Accumulation Hypothesis. Conversely, the Antagonistic Pleiotropy Hypothesis describes a mutation that is beneficial during early life but exerts negative effects in late life. The tradeoff between reproduction and survival is considered in the Disposable Soma Hypothesis. Two main categories of theories have been proposed for the aging process: In Program Theory aging follows a biological timetable under the guidance of a genetic program while Damage (or Error) Theory follows environmental assaults that cause physiological damages to accumulate and eventually result in loss of function and thus aging. In general, the evolutionary theories do not exclude each other and have received support from genetic studies. The physiological theories, however, are less in agreement. Recent studies in the Free Radical Oxidative Stress Hypothesis have made significant progress in the understanding of cellular aging pathways or senescence. These efforts may lead to further understanding of the aging processes.

並列關鍵字

ageing ； evolutionary biology ； physiological ageing ； free radical

參考文獻

Abrams, P. A., & Ludwig, D. (1995). Optimality theory, Gompertz’ law, and the disposable soma theory of senescence. Evolution, 49(6), 1055-1066.

Calcinotto, A., Kohli, J., Zagato, E., Pellegrini,L., Demaria, M. & Alimonti, A. (2019).Cellular senescence: aging, cancer, and injury.Physiological Reviews, 99, 1047-1078.

Carey, J. R., Liedo, P., Orozco D., & Vaupel, J. W.(1992). Slowing of mortality-rates at older ages in large medfly cohorts. Science, 258, 457-461.

Charlesworth, B. (2000). Fisher, Medawar, Hamilton and the evolution of aging. Genetics, 156, 927-931.

Charlesworth, B. (2001). Patterns of age-specific means and genetic variances of mortality rates predicted by the mutation accumulating theory of ageing. Journal of Theoretical Biology, 210,47-65.

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