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Providing a summary of the present state of aging research is a tall order, given the rapid growth in the field, and great breadth of work in both academia and industry, but the authors of this lengthy review paper take a swing at it. They look at areas of interest, new and well-established, apply a loose taxonomy to diverse initiatives, and attempt to draw it all together into a cohesive whole. The thrust of the field nowadays is towards intervention, attempting to slow or reverse aging in order to treat and prevent age-related disease. The important debates are over which strategies are more likely versus less likely to succeed in this goal, and thus over whether important areas of fundamental and preclinical research are underfunded or overfunded, and whether large-scale funding for clinical development is misplaced.
Aging has attracted curiosity and elicited imagination throughout human history. However, it has been only 30 years since a new epoch in aging research was established after the isolation of the first long-lived strains in C. elegans. Nowadays, studies in the aging field are exploding with the ever-expanding knowledge of the molecular and cellular bases of life and diseases, whilst subjected to scientific scrutiny. In this current review, we summarize the cutting-edge developments in aging research, presenting the landscape of aging across multiple layers.
In the first chapter, at the cellular level, we focus on cellular senescence, a main culprit of aging, harnessing a panel of phenotypes from various aspects to reveal underlying molecular alterations and mechanisms. In addition, cellular senescence bridges aging and cancer, for which aging is a major risk factor but the causal relationship still remains elusive. On one hand, cellular senescence constitutes a potent, cell autonomous anti-cancer mechanism in vivo of higher eukaryotes; on the other hand, cellular senescence accumulating with age may evoke intrinsic reprogramming of stem cells and contribute to tumor-promoting microenvironment through SASP and inflammaging.
Amongst all cell types, stem cell aging is of particular interest, as their exhaustion and dysfunction impair tissue function and regeneration capacity and lead to age-associated disorders, driving impacts way up to organismal aging. Indeed, aging is manifested as a multisystemic deterioration throughout the body that leads to declining tissue and organ functions. What we have learned about cellular aging from the first chapter are also reflected at the tissue level; and moreover, in this aging community of cells, they are affected by each other in the same tissue through the microenvironment, or even across tissues by systemic factors.
In the second chapter, we summarize aging-associated changes that occur in various tissues and organs, including those in the circulatory system, hematopoietic and immune system, nervous system, musculoskeletal system, reproductive system, digestive system as well as the microbiota therein. Collectively, understanding mechanisms and identifying targets of tissue/organ aging open vistas to therapeutic interventions for alleviating aging and age-associated disorders.
Finally, in the third chapter, we review geroprotective approaches in the hope to rewind the biological clock to a youthful state. This can be achieved by targeting key pro-/reverse-aging factors to rejuvenate aged cells, by eliminating senescent cells, or by transplanting genetically-modified stem cells. The rejuvenating effect can be local or systematic. Sophisticated strategies have been developed to deliver it through gene therapy, antibodies, or small molecule-based drugs.
We are now entering an inspiring era of aging research. According to new scientific findings summarized here and in other equivalent publications, this era now offers unprecedented hope for extending human healthspan: preventing, delaying or, even in certain cases, reversing many of the signs of aging. Whether this era promises to extend the longest human lifespan still remains an open question. However, what is clear is that after 30 years of fundamental research linking specific genes to aging, although many aspects still await further investigation, such as the interplay between metabolism and systemic aging, a solid foundation has been established, and clinical trials for interventions that target the aging process are being initiated. Although we may encounter considerable difficulties in applying this research to humans, the potential rewards in healthy aging far outweigh the risks.