Summary: Introduction to geroscience, a scientific field which aims to slow down human aging. Part 1 of a 4-part essay Geroscience by Felipe Sierra, which both updates the current status of, and provides a glimpse into the future of this field. [With an introduction by Brady Hartman. ]
Scientists in the emerging field of geroscience have significantly slowed down aging in laboratory animals and aim to the same thing for humans.
Felipe Sierra, Ph.D. is the Director of the Division of Aging Biology at the National Institute on Aging (NIA). Dr. Sierra is leading the U.S. government’s geroscience research efforts, with the aim of understanding why we age and looking for ways to slow down the aging process.
In his four-part essay titled “Geroscience,” Dr. Sierra 1) explains the field of geroscience and the importance of studying aging at the most basic biologic level; 2) updates us on the main current areas of aging research; and 3) provides us with a look into the future of the geroscience field and their plans to slow down the chronic diseases of aging by attacking the aging process itself.
The new field of geroscience aims to bridge the gap and increase the scientific understanding of the molecular and cellular underpinnings of aging that make it the main risk factor for disease and disability.
Key Points of the ‘Geroscience’ Essay
- Aging is the major risk factor for most chronic diseases and conditions affecting older adults.
- Longevity researchers (called geroscientists) have identified a finite number of factors that control the rate of aging at the molecular and cellular levels.
- Scientists can manipulate the rate of biologic aging to extend lifespan using a variety of behavioral genetic and pharmacologic interventions in many animal models.
- When these interventions decrease the rate of aging, it is most often accompanied by a delay in and decreased the severity of naturally occurring diseases as well as improved resistance to laboratory-induced diseases.
- Rapid progress in the lifespan extension field makes it likely that scientists will discover additional longevity pathways and drugs in the near future. Therefore, it is likely that clinically relevant advances will occur as a result of the studies on the biology of aging.
Sierra’s Background in Geroscience
After being trained as a biochemist in his native Chile, Felipe Sierra obtained a Ph.D. in Biochemistry and Molecular Biology from the University of Florida in 1983. After completing his postdoctoral at the University of Geneva, Dr. Sierra worked at Nestlé for the next five years. At this stage, he developed his interest in the biology of aging, an interest that brought him back to academia as an Assistant Professor at the Medical College of Pennsylvania, and later as an Associate Professor at the Lankenau Institute for Medical Research in the Keystone state. During this last position, Dr. Sierra divided his time with a position at the University of Chile in Santiago. Four years after initiating this arrangement, Dr. Sierra relocated back to the US, this time as a Program Director within the Division of Aging Biology, NIA. He became the Director of this division in April 2006.
Dr. Sierra is also the founder and coordinator of the trans-NIH Geroscience Special Interest Group (GSIG). The Geroscience Special Interest Group spans the entire NIH, and is built on the fact that aging is the major risk factor for most chronic age-related diseases – such as cancer, Alzheimer’s disease, cardiovascular disease, and more – and thus understanding the basic biology of aging is central to the ability of medical science to address these diseases. In 2013 and 2014, Dr. Sierra received the NIH Director’s Awards for this effort.
Geroscience (Section 1 – Introduction)
By Felipe Sierra, Ph.D.
From the biologic perspective, aging is a rather complex term to define. Aging is not a disease but, because aging is the main risk factor for so many chronic diseases and conditions, it is difficult to separate the two operationally. Richard Miller of the University of Michigan defines aging as the “process that progressively converts physiologically and cognitively fit healthy adults into less fit individuals with increasing vulnerability to injury, illness and death,”  and this seems like an adequate attempt. It separates aging from the associated chronic diseases (a domain best covered by geriatricians), but it also sets the stage for a recently blossoming new field linking the two areas, termed geroscience (http://en.wikipedia.org/wiki/Geroscience). [Link to article.]
A “cure” for aging—a fountain of youth—has been a dream of humanity throughout history. And, although aging is inevitable, it is easy to accept that humans age at different rates, so not all 70-year-olds are similar to each other in terms of health. It is also easily acknowledged that life span and health span can be extended simply by adopting moderate changes in lifestyle, including diet and exercise. Unfortunately, this is not easy for most people. Indeed, although public policy has managed to change most people’s behaviors in some domains (seatbelts, smoking, and putting babies on their backs represent successful recent examples), reversing behaviors concerning unhealthful habits in terms of diet and exercise is considerably more difficult. For example, it is known that in many laboratory animals, substantially reducing caloric intake extends life span and improves health in old age. [2,3]
Yet, very few people would have the willpower to subject themselves to the harshness of that regimen, and the entire area of dietary restriction (DR) is more suitable for experimental investigations than would be useful as a practical approach to human health.
There is a significant urgency in our need to address the issues posed by the increasing number of older people in the world, including both developed and developing countries. The most dramatic rise in the population is in those 85 years of age and older, including centenarians, and this poses challenges that as a species, we are not equipped to handle. In fact, in addition to the biology, our health care systems, economy, and the very fabric of society will be put to a test to absorb and handle this unprecedented increase in the proportion of older adults in the human population. [4,5] In addition to the obvious need for more properly trained geriatricians and social workers, there is also a need to understand the biology driving the aging process better as a way to diminish the ravages of old age.
Research on aging biology has exploded in the last few decades, from a relatively backward field focused on descriptive work that catalogued the many changes that occur during aging—first to a highly mechanistic phase driven by genetics, molecular, and cellular studies, and now to the current stage where, without neglecting the still unfinished mechanistic and discovery work, some of the findings are poised for possible application in humans. Interestingly, although there is a pervasive notion that aging is bad, and therefore all changes observed with aging should be reversed, research has shown that this is not really the case. This is because some age-related changes actually represent adaptive positive responses from an organism that by being alive, must strive to maintain homeostasis in the face of multiple challenges. So, although some age-related phenomena appear to be involved in increasing the risk for age-related disease (e.g., the decrease in proteostasis leading to neurodegenerative diseases), [6,7] others are neutral (e.g., cosmetic changes like hair loss), and some appear to be beneficial to the health of the organism. Attempts to reverse them might have unexpectedly serious consequences (e.g., changes in some hormones, possibly in testosterone [8,9] or insulin-like growth factor [IGF]).  Other changes are the result of pathology and are therefore independent of the aging process per se, yet they are difficult to separate in the case of highly prevalent diseases and conditions.
The main initial drivers of research into the biology of aging included caloric restriction, cell senescence, and the free radical hypothesis.  These are still active areas of research, but some of these have undergone significant rethinking. On the other hand, it is generally acknowledged that the main transformative research leading to the current status of the field was the genetic work initially encouraged by the National Institute on Aging (NIA) Longevity Assurance Genes Initiative (LAG). [11,12] At present, there are several hundred genes that when modified, can increase the life span in animal models.  Many of these fall into well-defined (and well-studied) pathways, but many remain orphans and are poorly studied or understood. Interestingly, in some cases, variant alleles of these same genes have been associated with extended longevity in human centenarian studies.  Although there is wide recognition of the partially inheritable nature of longevity, the finding that individual genes, when manipulated, could lead to dramatic increases in longevity was not expected and was initially greeted with skepticism. Nevertheless, the finding of molecular drivers of the process brought aging biology research into the mainstream and has resulted in the current renaissance of the field. These events have been reviewed previously and will not be repeated here. [11,12] Rather, in this chapter I will focus on the following: (1) the main current areas of research; (2) a discussion of geroscience and the importance of studying aging at the most basic biologic level; and (3) a look into future prospects and needs, based on the current status of the field.
– by Felipe Sierra, Ph.D. [Editor’s note: this article continues in additional sections.]
Geroscience Article Continues in 4 Sections
- Part 1 of 4: Geroscience – Introduction (this article).
- Part 2 of 4: The Main Pillars of Research on Aging Biology (the main areas of lifespan-extension research).
- Part 3 of 4: Geroscience (explains the geroscience field).
- Part 4 of 4: A Tentative Look into the Future (ways geroscience hopes to increase life span).
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References Accompanying this Section of Geroscience
(References provided by Dr. Felipe Sierra in Geroscience.)
1. Miller RA: Kleemeier award lecture: Are there genes for aging? J Gerontol A Biol Sci Med Sci 54:B297–B307, 1999.
2. McCay CM, Crowell MF: Prolonging the life span. Sci Mon 39:405–414, 1934.
3. McCay CM, Crowell MF, Maynard LA: The effect of retarded growth upon the length of life span and upon the ultimate body size. J Nutr 10:63–79, 1935.
4. Olshansky SJ: Can a lot more people live to one hundred and what if they did? Accid Anal Prev 61:141–145, 2013.
5. Battacharya J, Cutler DM, Goldman DP, et al: Disability forecasts and future Medicare costs. In Cutler DM, Garber AM, editors: Frontiers in health policy research, vol 7, Cambridge, MA, 2004, National Bureau of Economic Research, pp 75–94.
6. Fink AL: Protein aggregation: folding aggregates, inclusion bodies and amyloid. Fold Des 3:R9–R23, 1998.
7. Chiti F, Dobson CM: Protein misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366, 2006.
8. Matsumoto AM: Testosterone administration in older men. Endocrinol Metab Clin North Am 42:271–286, 2013.
9. Corona G, Vignozzi L, Sforza A, et al: Risks and benefits of late onset hypogonadism treatment: an expert opinion. World J Mens Health 31:103–125, 2013.
10. Rincon M, Rudin E, Barzilai N: The insulin/IGF-1 signaling in mammals and its relevance to human longevity. Exp Gerontol 40:873–877, 2005.
11. Warner HR: Developing a research agenda in biogerontology: basic mechanisms. Sci Aging Knowl Environ 44:pe33, 2005.
12. Warner HR: 2006 Kent award lecture: is cell death and replacement a factor in aging? J Gerontol A Biol Sci Med Sci 62:1228–1232, 2007.
13. Kenyon C: The genetics of aging. Nature 464:504–512, 2010.
14. Wheeler HE, Kim SK: Genetics and genomics of human aging. Philos Trans R Soc Lond B Biol Sci 366:43–50, 2011.
Cover photo courtesy of Dr. Felipe Sierra and the NIH.
National Institute on Aging. “Felipe Sierra.” National Institutes of Health. Web, Retrieved 10 Jan 2018. Link to Article.
Felipe Sierra. “Geroscience.” Brocklehurst’s Textbook of Geriatric Medicine and Gerontology, 8th Edition, Authors: Howard Fillit Kenneth Rockwood John B Young. ISBN: 978-0-7020-6185-1
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