针对近期细胞杂志发表的所谓引领科学前沿的综述文章“The Hallmarks of Aging”，我们提出了直截了当的评论和“天问”，指出该文有三条重要缺陷。1）混淆了病理性衰老与生理性衰老的重大差别； 2）所列出的“衰老指标”极其偏颇，忽略了大量与蛋白质衰老相关的重要指标； 3）对于衰老本质缺少正确地和深刻地认识。

经过与《细胞》杂志编辑部的反复交涉和据理力争，我们的评论现已在线发表。读者可先点击该文：http://www.cell.com/abstract/S0092-8674(13)00645-4#Summary. 然后点击 Comments 可见我们的评论。欢迎大家前往，共享“天论”之乐。

附, 最终按编辑部的要求，浓缩精炼的评论文字如下:

“The Hallmarks of Aging” Needs Revision

^*Dazhong Yin,Jun Gao, Bruce A Carnes

* Correspondence: dazhongyin002@126.com

     "The Hallmarks of Aging" published in the journal Cell was informative and contained a series of brilliant concepts (Lopez-Otin, et al. 2013).  However, some important  shortages shadow the  merits of  this article.

The review started with a clear definition: “Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death.” Unfortunately, the review failed to discuss details of the physiological degradation that arises from aging and instead focused on disease pathologies. From our perspective, a healthy centenarian can die from aging without any clear evidence of clinically defined degenerative disease. Therefore, conflating physiological aging with aging-associated disease is a major conceptual flaw in the paper that can mislead research efforts in the field of biogerontology.

We were also surprised to read that “This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms”, without mentioning legitimate biomarkers of aging such as lipofuscin, wrinkled skin, stiffened blood vessel, increased amyloidosis, aging-dependant tissue fibrosis and collagen crosslinks of the extracellular matrix etc. (Yin and Chen, 2005). Instead of “The Hallmarks of Aging” this paper would have been more appropriately entitled "Hallmarks of Aging-related Diseases and Their Genetic Relevance".

A profound and accurate understanding of aging was an important omission in the paper, such as the very essence of aging mechanisms, which should have provided the backbone of this review. The details of an improved understanding of aging were published over 8 years ago and have been widely supported in the scientific literature (Yin and Chen, 2005; Holliday, 2006; Hayflick, 2007; Carnes, et al. 2013). Among those mechanisms, two fundamental biochemical side-reactions (oxidative stress and glycative stress) were identified as resulting in a common pathway of entropy-substantiated irreparable crosslinking that defines the essential biochemistry of aging (Yin, 1996; Yin and Chen, 2005). When irreparable carbonylation was found to be physiologically lethal, the biophysical essence of aging became explainable at a sub-molecular level (Yin and Chen, 2005) - the chemically functioning group level. In essence, it is the electron philic/phobic chemistry of life which is the driving force behind most, if not all, of the aging-related alterations and their irreparable damage accumulation. In other words, aging is a war between physicochemical damage and maintenance of the soma (Hayflick, 2007). As such, real aging process involves mainly physiological alterations, which are largely irreparable but endurable in healthy body. Genomic damages (DNA mutation of progerias, epigenetic alterations, telomere shortening in certain type of cells, mitochondrial DNA damages), due to a “snowball effect”, play a key role in the etiology of pathologic changes (Yin and Chen, 2005; Hayflick 2007).

Moreover, this physiological explanation of aging is not limited to the human and animal kingdom, but applies to all forms of life.

REFERENCES

Carnes, B.A., Olshansky, S.J. and Hayflick, L. (2013). Can human biology allow most of us to become centenarians? J. Gerontol. A Biol. Sci. Med. Sci. 68, 136-142.

Hayflick, L. (2007). Entropy explains aging, genetic determinism explains longevity, and undefined terminology explains misunderstanding both. PloS Genetics 3, e220.

Holliday, R. (2006). Aging is no longer an unsolved problem in biology. Ann. N.Y. Acad. Sci. 1067, 1-9.

Lopez-Otin, C., Blasco, M.A., Partridge, L., Serrano, M., and Kroemer, G. (2013). The hallmarks of aging. Cell 153, 1194-1217.

Yin, D. (1996). Biochemical basis of lipofuscin, ceroid, and age pigment-like fluorophores. Free Radic. Biol. Med. 21, 871-888.

Yin, D., and Chen, K. (2005). The essential mechanisms of aging: irreparable damage accumulation of biochemical side-reactions. Exp. Gerontol. 40, 455-465.

以下是“衰老表征”作者们的回复：

（http://www.cell.com/abstract/S0092-8674(13)00645-4#Comments）

    We thank Dazhong Yin and colleagues, and by
Shi Liu for their comments.

    Some aspects of aging mentioned by Yin and colleages, such as wrinkled
skin,stiffened blood vessels, amyloidosis, and others are likely related to
defects
in the extracellular matrices of tissues. Actually, some of these
aspects are already covered in two specific hallmarks: “Loss of proteostasis”
and “Altered intercellular communication”.

    We are aware of some additional work
relating
defects in extracellular matrix production and premature aging, however, on the whole, we have considered that this candidate hallmark has not
achieved
yet the same level of evidence as the other hallmarks included in the
Review.


附：世界一流衰老学家感谢刘实、印大中批评但仍找不到北