Chapter 71

Thanks largely to the power of genetic analysis in model organisms such as Caenorhabditis elegans (a nematode), Drosophila melanogaster (a fruit fly), and the laboratory mouse, major advances have been made in the elucidation of what can be termed "public" modulations of intrinsic biological aging—that is to say, commonalities of gene actions across widely diverse phyla that explain, in part, the plasticity of processes of aging. There are hints that at least one such conserved pathway may be operative in our own species. These observations, together with related research on other biochemical pathways, a long history of research on the beneficial effects of dietary restriction (most recently including an initial report of its beneficial effects on healthspan and lifespan in a primate) (Fig. 71-1), and spectacular advances in genomics raise the possibility that we may one day be able to delay the times of onset and decrease the rates of progression of aging processes. Such interventions have the potential to extend the healthspans and, therefore, the functional lifespans of a large proportion of our population. This new knowledge, however, is still very distant from clinical translation. Many remain skeptical of the relevance of these experimental findings. Moreover, we need much more information on the pathophysiology of aging, especially in the invertebrate models that have provided most of our new knowledge concerning genetic modulations of lifespan. We will also require more detailed information on the impact of longevity enhancements upon what can be described as the "terminal decline" of the life course, the stage of life in humans responsible for protracted morbidity, frailty, and the consequent loss of the ability to live independently. These terminal declines account for a very substantial proportion of all health care costs. Finally, the promising new knowledge needs fuller discussions by ethicists, economists, sociologists, and political scientists, among others, as to the impacts upon society of any large-scale clinical translations.

###### Figure 71-1

Photographs of an old (age 27.6 years) calorically restricted (CR) Rhesus monkey (A, B) compared to an age-matched control (C, D). The mean lifespans of control animals in captivity is 27 years and the maximum lifespan is about 40 years. CR (30% of ad libitum fed controls) was initiated as adults (ages 7–14 years). Restricted animals exhibited superior insulin sensitivity, less fat, more muscle mass, and fewer diseases (diabetes, neoplasia, cardiovascular, brain atrophy). Preliminary analyses of survival curves were consistent with enhanced longevity of the CR cohort. (Reproduced from RJ Colman et al: Science 235:201, 2009; with permission.)

### Definitions of Aging: Senescent Phenotypes

Mammalian gerontologists usually define aging in terms of ...

Sign in to your MyAccess Account while you are actively authenticated on this website via your institution (you will be able to tell by looking in the top right corner of any page – if you see your institution’s name, you are authenticated). You will then be able to access your institute’s content/subscription for 90 days from any location, after which you must repeat this process for continued access.

Ok

## Subscription Options

### AccessMedicine Full Site: One-Year Subscription

Connect to the full suite of AccessMedicine content and resources including more than 250 examination and procedural videos, patient safety modules, an extensive drug database, Q&A, Case Files, and more.