Animal research on preventing aging

Who Wants to Live Forever?

Biogerontology (the study of the biological aspects of aging) is a particular field of research that is struggling for recognition by the scientific community as a proper intellectual domain. One impeding factor is the difficulty to separate this field of study from the “anti-aging” industry, which have somewhat of a blemished history and tarnished reputation. Nevertheless, biogerontology has slowly started to become more accepted and, in parallel, the interest in age-related research has started to boom. So if these scientists are not just producing anti-aging products, what are they doing?

The Puzzling Questions
Separating the anti-aging industry from the work of a biogerontologist is difficult, mainly because they are trying to achieve similar ends. However, for a biogerontologist, the focus is to understand what aging is (a solid definition is still lacking) as well as to understand the aging process. Ultimately, their goal is to alter the degenerative process of aging and thus to keep people healthy and fully functional up until the time of death [1].
The intriguing thing about biogerontology is that the most basic questions still remain unanswered. As such, it is a field of study where possible breakthroughs may lurk in the distance. One fascinating question includes why some species in general live longer than others (reference inter-species aging article?). Getting old is a universal across all species, yet horses generally live longer than rats but have shorter lives than humans. Aging affects species in a similar fashion, such as losing hair and muscle tone, getting age-related diseases etc. Yet, these happen at a differential rate across species. We still do not know why this is the case [1].

The “supermodel” of age research – the naked mole rat
Picture source: http://bit.ly/1n4aVZa

What are They Working On?
When it comes to investigating the lifespan, biogerontologists have often turned to genetics. Several genetic pro-longevity mutations have been identified by the usage of model organisms such as yeast, fruit flies and mice. Most of the identified genes are involved in aspects specific to evolution, including growth regulation, energy and reproduction.

NAKED MOLE RATS LIVE 10 TIMES LONGER THAN NORMAL LAB RATS

Apart from genetics, specific prominent models have emerged. One model that especially has attracted attention is the so-called “Naked mole rat” – also known as the “supermodel” of age research. The mouse-sized rat is normally found in the horn of Africa and has a marvelous lifespan of 30 years (!), as compared to the average 3 years of a normal lab rat [2]. Its long life span has been linked to its good health and cancer resistance. So obviously some processes have evolved in these species that allow them to stay fit for such a long time in comparison to a lab rat. Surprisingly enough, these rats exhibit high levels of oxidative stress and short telomeres – findings usually linked to an accelerated aging process. Yet, despite this, they still cope well with cellular stressors and show stable genetic integrity. The mechanism of how they are able to do this still remains a mystery [3].

Any Breakthroughs Yet?
There is still a lot which remains to be discovered. Yet, one major finding in aging research is that dietary restriction (under-feeding with a 30-40% reduction in calories, without malnutrition) extends life in both nematodes, spiders and dogs. The idea that life is prolonged during times of less food is thought to serve as an evolutionary advantage, as this enables animals to postpone reproduction until food is available. The underlying mechanism is unclear, yet the hypothesis is that decreased caloric intake slows down metabolic activity, thus reducing the production of toxic reactive oxygen species and ultimately the aging process [4,5].

CALORIC RESTRITION EXTENDS LIFE IN DOGS, SPIDERS AND NEMATODES

Can We Extend Life?
Biogerontologists do find that different genes/pathway/processes are involved in the aging process when investigating different species. Despite this, translational approaches are challenging as aging processes, while bearing similarities across species (e.g. the effect of dietary restriction), also substantially differ from one another (naked mole rat vs a lab rat). This brings us to the general problem of translating preclinical findings into something useful in the clinics. Considering that we still need to understand the basic mechanism of aging, there is a long way to go before eternal life is possible. We will all eventually “suffer” from getting old. Yet, who knows? Given the increased interest in biogerontology, aging might with time (ironically) become a process which, to some extent, can be postponed or at least improved.

[1] Settersen et al., J Aging Stud, 2008
[2] Sengupta, Int J Prevent Med, 2013
[3] Edrey et al., ILAR J, 2011
[4] Guarente & Kenyon, Nature, 2000
[5] Vijg & Campisi, Nature, 2008

by Henriette Edemann Callesen, PhD student AG C.Winter
this ariticle originally appeared in CNS Volume 9, Issue 1, The Aging Brain

Forever Young: Lessons in Longer Living from Around the World

Who does not want to stay forever young? Some people are blessed with a healthy body even in old age, others seem older than they really are. What is the secret behind that and is there a "fountain of youth"?

Aging - Our Enemy

We have all experienced a feeling of panic and unease at some point when thinking about our age. It usually first hits us as we approach 30, but also probably returns when we retire. Reasons for this may lie in the expectations we have for ourselves at the age of, let’s say, 18, when looking into our future. We expect to look at an extensive summary of our huge achievements, a clear purpose we served and a (mostly) fully functional body and mind. But finding us far from this ideal position can have disillusioning effects. So how can we learn to live the right way from people who have already gone far?

GENETICS CONTRIBUTE TO ONLY 20-30% OF A LONG LIFE

Longevity expert Dan Buettner and his team fathered the term “Blue Zones” to describe little corners on Earth where people live on average a longer and healthier life than the ‘western’ countries. Their lifestyles add 7-11 years to the average western life expectancy. Their huge cluster of over 90-year-olds is as impressive as the striking number of 80- to 90-year-olds of the Blue Zone populations that experience Alzheimer's and dementia - just a fraction of western incidence rates [1]. Based on this information, one might think that these Blue Zones populations might have cracked the secrets of longevity.

Old People crossing by Schnaars via Flickr

Mapping the Blue Zones

Three examples of Blue Zones are the Japanese island of Okinawa, parts of the Italian island of Sardinia and Loma Linda in California, USA, each of which independently developed their own ways of life.

Okinawans follow strongly Confucius’s theories, which are ‘moais’: keep lifelong friends (which also serve as close social support groups), ‘hara hachi bu’ (eat until you are 80% full) and ‘ikigai’ (find a purpose for which you wake up every morning). 

EAT UNTIL YOU ARE 80% FULL

Part of the reason for Sardinia’s longevity may be genetic, but scientists believe that only 20-30% of the adult lifespan is accounted for by genetic factors [2]. The Mediterranean diet might explain their longevity. They eat lots of goat cheese and other omega-3 rich foods, drink red wine in moderation and walk a lot, but also take their time for leisure and share the work burden with their spouses.
The religious group of Adventists in Loma Linda integrated their healthy habits to their belief system, by eating lots of nuts and beans high in mono- and polysaturated fats, fibers and various vitamins which are believed to contribute to health [3]. It is not known whether nuts contain something that extends life or whether their consumption just indicates a healthy lifestyle in general. They also drink plenty of water, exercise regularly and value their family relationships.
Now, reading this, one might get the idea of how to live the ‘right’ way in order to live a long and healthy life. What do the Blue Zone populations have in common? And what is so different compared to our ways of life?

Make the Life Years Count

Dan Buettner and his team summarized the common components of Blue Zones into 4 main points [4]:
(1) All cultures move naturally and constantly using every single occasion. In our society the idea of exercise mostly means to work out for only 30-60 minutes every two or three days, whereas we forget our urge for exercise when we have to decide whether to take the stairs or escalator.
(2) The Blue Zones know how to live with the right outlook to life. Each of these cultures take time to relax by praying or caring for ancestors. When we are in a hurry and stressed out, our bodies trigger inflammatory responses that are associated with all kinds of disorders, from Alzheimer’s to cardiovascular disease. Slowing down for a few moments may turn these responses to anti-inflammatory responses.
(3) There is no longevity diet, instead these people drink a little bit of red wine, they tend to eat plant-based diets and have strategies that prevent overeating. Despite the increasing awareness of healthy nutrition, the vast majority of the western population is careless about what and how they eat.
(4) The foundation of all of this is how Blue Zone populations connect. They put their families first, take care of their children and aging parents and belong to a faith-based community. But the most important point is they belong to the right tribe, either by being born in it or by pro-actively surrounding themselves by the right people. Both healthy and unhealthy lifestyles of our loved ones, such as our friends, will probably have a measureable impact on our behavior over time.
When it comes to longevity there is no short-term treatment or miracle pill. But when you think about it, choosing the right friends is probably the most significant long-term action we could take to “add more years to our lives and more life to our years” [5].

[1] www.bluezones.com
[2] vB Hjelmborg et al., Hum Genet, 2006

[3] Salas-Salvadó et al., Br J Nutr, 2006

[4] Buettner, The Blue zones : Lessons for Living Longer From the People Who've Lived the Longest, 2009

[5] Quoting Ralph S. Paffenbarger, Jr. (October 21, 1922 – July 9, 2007), epidemiologist.

by Anahita Poshtiban, PhD student AG Plested
this article originally appeared in CNS Volume 9, Issue 1, The Aging Brain