前一篇博文简述了《细胞》近来的一篇“小样儿”的综述，今博文给出准备投给该杂志的英文评论，很有点火药味。

   再后面给出与美国知名学者的通讯往来情况，探讨本博写的这一篇英文评论，这里同样也请大家批评指正！

“The Hallmarks of Aging” Needs Revision

* Correspondence: dazhongyin002@126.com

Although being informative and with some brilliant concepts such as cancer and aging are from a same track, it is root and branch incredible to read a leading edge review of “The Hallmarks of Aging” being published recently in the journal 《Cell》without mentioning various real physiological phenotypes of aging (Lopez-Otin, et al. 2013).Despite that the review is not emphasizing on “the biology of aging mechanisms”, aging mechanisms are the backbone of this review, however a correct understanding of healthy aging seems missing (Yin, 2003; Yin and Chen, 2005; Holliday, 2006; Hayflick, 2007; Carnes et al. 2013).

The review started with a clear definition indicating “Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death.” However, it is regretful to recognize that the most part of the review was not served to discuss the physiological aberrant or alterations of aging, rather pathological phenotypes, typically gene deterioration-based progerials, cancer or other degenerative diseases (Lopez-Otin, et al. 2013). Though the point has been stated by the authors in their abstract: “This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases”, it is not acceptable and actually misleading to mix up  and replace physiological aging, the real aging, with aging-associated diseases. Our argument hereby is simple, a real aging death can well happen to an aged healthy centenarian without any clear evidence of clinically well defined degenerative diseases.

We were also surprised to read that “This review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms”, without mentioning those most significant real aging-related hallmarks such as lipofuscin, wrinkeled skin, stiffened blood vessel, increased amyloidosis, aging-dependant tissue fibrosis and collagen crosslinks of extracellular matrix etc. (Yin, 1996; Yin and Chen, 2005). The aging hallmarks listed in the review are mainly pathological: “genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.” By reading through the whole article, we hardly believe this is a review of “The Hallmarks of Aging ”. It is more like a paper on some hallmarks of aging-related diseases and their genetic relevance.

After eight years when the essential mechanism of aging has been revealed and agreed by a number of professional international gerontologists (Yin and Chen, 2005; Holliday, 2006; Hayflick, 2007; Carnes, et al. 2013), two fundarmental biochemical side-reactions, oxidative stress and glycative stress, have been extracted and assembled to a common irreparable entropy-substantiated crosslinking biochemistry (Yin, 1996). When irreparable carbonylation was found to be physiologically lethal, the biophysical essence of aging was thus recognized and pinpointed to interpretating aging at a submolecular level (Yin and Chen, 2005), the chemically functioning group level. It is the electon philic/phobic chemistry which is the driving force behind most, if not all, the aging-related alterations and their irreparable accumulation. Aging is a war between physicochemical damage and maintenance largely in physiological scope beyond pathology (Hayflick, 2007; Holliday, 2010). Most genomic damages, however as reviewed: the DNA mutation of progerials, epigenetic alterations, telomere shortenning in certain type of cells, mitochondrial DNA damages, all result in typical patholoical changes (Yin and Chen, 2005).

Moreover, this explanation of aging essence is not only valuable in the human and animal kindom, but also valid broadly in all other biological kindoms.

When the mechanisms of healthy aging, the real physiological aging, become clear, all pathological aging should not be included into the stricktly defined aging field. No matter how successful a batter against the pathological aging may achieve, the physiological aging and/or the humans maximum life-span may not be really affected, except only when the whole genetic system of maintenance may be altered.

Nevertheless, the hallmarks of aging povided in this review needs a serious revision, at least to include various physiological indexes of aging. When the hallmarks as well as pharmaceutical targets of aging are correctly referred, the batter against aging may then approach to the right direction.  

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.

Holliday, R. (2010). Aging and the decline in health. Health 2, 615-619.

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

Yin, D. (2003). Aging: a war between life and entropy. Chi. J. Gerontol. 23, 555-559.

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.

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