Re: Understanding Anti Ageing
Violetta Wagganer
Key objectives of biogerontology are to understand the biology of aging and to translate scientific insight into interventions that improve late-life health - or anti-aging treatments. In this context, when considering the problem of how to effect translational research, it is useful to have a clear, consensus view on what exactly constitutes an anti-aging treatment. This essay critically assesses the understanding of this concept common among biogerontologists, and proposes a new definition. A current conception of anti-aging treatment imagines a primary cause of aging that is causally upstream of, and the cause of, all age-related pathology. Intervening in this aging process thus protects against the totality of age-related diseases. However, this underlying aging process remains an abstraction. By contrast, what is demonstrable is that interventions in model organisms can improve late-life health and extend lifespan. Furthermore, a safe deduction is that treatments that extend lifespan do so by reducing age-related pathology, both florid and subtle. What is currently identifiable about aging (i.e. senescence) is that it is a very complex disease syndrome, likely involving a number of biological mechanisms. Treatments that substantially extend lifespan must suppress multiple pathologies that otherwise limit lifespan, but whether they suppress the entire aging process remains undemonstrated. A more pragmatic and realistic definition of anti-aging treatment is any preventative approach to reduce late-life pathology, based on the understanding that senescence is a disease syndrome. This definition would encompass preventative approaches aimed at both broad and narrow spectra of age-related pathologies. Its adoption would facilitate translation, since it would shift the emphasis to medical practice, particularly the introduction of preventative approaches. Narrow spectrum anti-aging treatments (e.g. the cardiovascular polypill) could establish a practice that eventually extends to broader spectrum anti-aging treatments (e.g. dietary restriction mimetics).
Result: A total of 27 potential therapeutic targets were screened out. Seven hub targets (PPARA, CAT, MAPK14, SQSTM1, HMOX1, GRB2, and GSR) were identified. Functional and pathway enrichment analysis indicated that these 27 putative targets exerted therapeutic effects on oocyte aging by regulating signaling pathways (e.g., PPAR, TNF, apoptosis, necroptosisn, prolactin, and MAPK signaling pathway), and are involved oxidation-reduction process, mitochondrion, enzyme binding, reactive oxygen species metabolic process, ATP binding, among others. In addition, five densely linked functional modules revealed the potential mechanisms of CoQ10 in improving aging-related deterioration of oocyte quality are closely related to antioxidant, mitochondrial function enhancement, autophagy, anti-apoptosis, and immune and endocrine system regulation. The molecular docking study reveals that seven hub targets have a good binding affinity towards CoQ10, and molecular dynamics simulation confirms the stability of the interaction between the hub targets and the CoQ10 ligand.
Conclusion: This network pharmacology study revealed the multiple mechanisms involved in the anti-aging effect of CoQ10 on oocytes. The molecular docking and molecular dynamics simulation provide evidence that CoQ10 may act on these hub targets to fight against oocytes aging.
Ageing refers to the various processes of wear and tear that affect us continuously. Even if people argue over what drives any or all of those processes, they all seem to agree on how they affect us: perceptibly as well as imperceptibly, they make us prone to falling apart. Not surprisingly, the search for remedies against the ageing process, and the study of human ageing itself, has a long history in numerous cultural traditions around the world. Traditional Chinese medicine has always maintained a keen interest in the arts of extending human lifespan and attaining immortality in the flesh. 'Fountain of youth' remedies abound in Chinese medicine, and legends of immortals living on mountaintops have been a constant in its folklore. Western science also has a long history of preoccupation with the arts of prolonging human lifespan (Gruman, 2003). One example of early protoscientific attempts in the Western world to develop effective, systematic means of life extension is Makrobiotik by the German physician Christofer Hufeland (Hufeland, 1798), which contained advice about diet and lifestyle that the author recommended for prolonging life.
Gerontology, in the modern meaning of the term, did not take form until about a century later, when the French physician Jean Martin Charcot published his famous Clinical Lectures on the Diseases of Old Age (Charcot, 1881). It initiated gerontology as a study of the bodily changes and pathologies that accompany ageing. But if the late nineteenth century's medical gaze introduced systematic investigation of physiological and biological processes associated with senescence, it did not, however, put an end to the age-old quest for magical 'fountain of youth' potions, often disguised as scientific remedies for restoring youth and vitality. Ironically, around the time of Charcot's lectures, another respected French medical researcher, Charles Édouard Brownséquard, claimed that the consumption of extracts from crushed dog testicles would allow old men to regain their potency (Gosden, 1996).
The most visible aspect of this change is the success of the anti-ageing industry that caters to the needs of the elderly. Like alternative medicine, it owes much of its success to its fundamental, albeit ambiguous, relationship with science. This particular sector in consumer society is shrouded with an aura of science that is used for the promotion of a variety of goods. It thrives on symbolic uses of science, while passing over its requirements for experimental evidence, peer review and official regulations. The aura and the discourse of science are skilfully applied for product enhancement in response to a fast-growing demand from the ageing public (see McConnel & Turner, page S59).
The anti-ageing market is replete with products: yoghurt cures, enema regimens, cell injections, magnetic devices, skin creams, herbal elixirs, glandular extracts, hormonal therapies, vitamin supplements, fad diets and exercise programmes. They give us anti-oxidants to neutralize oxygen-free radicals; chelators to bind heavy metal ions such as copper and iron; dehydroepiandrosterone to rejuvenate the immune system, improve brain function and relieve stress; growth hormone to increase muscle mass and function; retinoic acid to decrease skin wrinkling, and many more. Recently, scientists have begun to object to what they see as excesses in the burgeoning business of 'false promises' and commercialization of science (Olshansky et al, 2002). These critics emphasize the distinction between the anti-ageing industry and the scientific field of 'biogerontology'. Biogerontology has grown into a subfield in biology in which researchers not only study the complex causes for the physiological failure to maintain homeostasis, but also the ways and means to slow down, arrest or even reverse degenerative processes in living organisms.
Consequently, three main paradigms or research orientations have been distinguished in biological research on ageing (Juengst et al, 2003): 'compressed morbidity', 'decelerated ageing' and 'arrested ageing'. Compressed morbidity refers to the most conventional of these research agendas. Its goal is to forestall all chronic ailments of old age by intervening in the underlying molecular processes. In this model, the ultimate goal is to seek increases in average human life expectancy, but not in maximum human lifespan. Realization of this paradigm should result in a society with many more old people who have active roles until their final, swiftly fatal, decline.
As a considerably more ambitious agenda, the decelerated ageing approach seeks to slow down the fundamental processes of ageing to the extent that average life expectancy and maximum lifespan are increased. Finally, the most radical of the three research approaches seeks to 'cure' ageing. The goal of arrested ageing is to continually restore vitality and bodily function by removing the damage that is inevitably caused by metabolic processes.
The rationale and the methods for obtaining compressed morbidity are non-controversial in the research community. Those who adhere to either of the other two paradigms may regard it as overly conservative, but in no way objectionable. Moreover, all members of the public who are open to the idea that science can be used to improve the human condition easily support the compressed morbidity agenda. Hence, a substantial amount of publicly funded basic research has been carried out and is being planned in the USA, Japan and Europe.
A number of essays in this special issue therefore address the questions of how time is embodied and how it results in 'ageing' of the organism. They point to how these processes can be studied scientifically. Life is a form of metabolism with potentially damaging side effects, and those side effects accumulate in our bodies over time. Many of these changes become pathogenic, and, together, they drive the ageing process that makes us frail and eventually kills us. The first part of this special issue of EMBO reports therefore contains a comprehensive representation of how life scientists now study the nature of these changes, and the possible means to counter the damage caused by ageing.
Within key Western societies, there are genuine negative perceptions, prejudices, and discriminations targeted against Muslims. Seeing Muslims as not loyal, voicing prejudice against Muslims, and avoiding Muslims as neighbors are all symptoms of Islamophobia that exist in the West. However, these feelings do not characterize Western countries. They are generally shared by a subset of the general population, though they exist in substantial enough numbers to draw both attention and concern. The very existence of Islamophobia is something to be addressed. The degree to which individuals expressing Islamophobia have particular views of Muslims in their communities, Muslims globally, and Islam as a religion is genuine and quantifiable with measurable outcomes.
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