Bernard L. Strehlera
aMolecular Biology Division, Department of Biology, University Southern California, Los Angeles, California, 90089, USA
Received 31 July 1986; accepted 25 August 1986. Available online 21 January 2003.
Abstract
The origins of aging of higher forms of life, particularly humans, is presented as the consequence of an evolved balance between 4 specific kinds of dysfunction-producing events and 4 kinds of evolved counteracting effects in long-lived forms. Among the deleterious events, particular importance is assigned to damage to DNA, but damage of a different kind than classical mutations. The evolution in man's ancestors of means to counteract the kinds of events that limit the life-spans of short lived mammals is postulated to be the indirect consequence of the prior evolution of superior mental capacities. Further, it is shown that the human species rapidly evolved its life-extending mutations because of the special circumstances afforded by the subdivision of the species into small semi-isolated (genetically) tribes of 10–100 individuals in which polygamy was the key factor in rapid incorporation of life- and well-being-extending new features. These conditions permit at least one or two orders of magnitude more of such beneficial genes to have been incorporated into our genomes during the 100,000 years or so of extremely rapid human evolution that evidently occurred about 100,000 to 200,000 years age than has been posited by other workers. The sources of damage to DNA are then considered, with special emphasis on free-radical derivatives of molecular oxygen and evidence is presented that longer lived forms of mammals have peroxide lysing enzymes that produce a lower steady state of damaging radicals derived from this compound. Evidence that so-called “classical” mutations cannot be the source of aging is then reviewed. A different kind of mutation, one that is not increased in proportion to point mutations by mutagens, namely deletio of tandemly duplicated copies of genes, is discussed and the evidence that such damage (gene loss) occurs in an amount sufficient to account for the major losses in function during aging is presented. The most likely mechanisms of such loss plus the prospects for evolving and bio-engineering means to counteract these losses together with some implications regarding the documented loss of of NORs with age (as regards rDNA loss) together with key areas for intensive present and future research on aging are presented.
老化的起源更高形式的生命，特別是人類，是作為一個演變的後果之間的平衡4種功能障礙的具體生產活動和四種演變抵消影響的壽命期長的形式。
其中的有害活動，尤其重要的是分配到的DNA損傷，但損傷是一種不同的比傳統的基因突變。
在人的進化祖先的手段應付的各種事件，限制了生命的短暫跨越哺乳動物是假設是間接的後果，事先演化上級精神的能力。
此外，它結果表明，人類迅速發展的生命延長，因為突變的特殊情況提供了細分的物種 into small半，隔離（基因）部落10-100個人在其中的一夫多妻制是關鍵因素在迅速將生活和福祉，提供新的功能。
這些條件允許至少一或兩個數量級以上的這種有益的基因已被納入我們的基因組在10萬年左右的人類進化非常迅速，顯然發生約 10萬至20歲年齡比人們設想的其他工人。
該來源的DNA損傷，然後考慮，特別強調自由基衍生物的分子氧和證據，提出了較長的居住形式的哺乳動物有過氧化溶解酶，產生一個穩定的狀態下破壞自由基來源於這種化合物。
有證據表明，所謂的“經典”突變不能老化的源，然後進行審查。
一種不同的突變，一個是沒有增加的比例由誘變突變點，即deletio的串聯重複拷貝基因，進行了討論並有證據表明這種損害（基因缺失）發生在一個足夠數額佔主要在衰老過程中的損失函數，提出。
最可能的機制，這種損失，加上前景變化和生物工程的手段來抵消這些損失連同有關文件的一些問題的NORs的損失與年齡（關於 rDNA的損失）以及重點領域深入研究當前和未來關於老齡化出現的。
其中其所稱的四種障礙是普遍性，有害性、漸進性、內因性。
