Elsevier

Vaccine

Volume 18, Issue 16, 25 February 2000, Pages 1567-1583
Vaccine

Diseases of aging

https://doi.org/10.1016/S0264-410X(99)00489-2Get rights and content

Abstract

By definition, diseases of aging become clinically manifested in elderly patients. However, their pathogenetic basis has to be sought earlier in life. The general thread of this presentation relies on the concept of an evolutionary-Darwinian view of the development of age-related diseases. In essence, this concept states that we may have to “pay” for genetic traits that play a beneficial role earlier in life by the later development of diseases since there is no post-reproductive selective pressure that may have eliminated the potential late onset detrimental effects of such genes. Examples for this kind of trade-off are taken from diseases involving the immune system (infections), the endocrine system (andropause), the nervous system (Alzheimer’s disease), the locomoter system (osteoporosis), the cardio-vascular system (atherosclerosis) and cancer.

Introduction

During the past century, mankind has gained more years of average life expectancy than in the last 10,000 years. Twenty percent of the population in the industrialized world is over 60 years of age, and the proportion of those over the age of 85 is growing six times faster than the population as a whole. Socioeconomically, the elderly have become the major problem of modern society, as exemplified by the fact that the largest health care expenditure is made during the last year of life and the requirement for nursing home beds is expected to increase fourfold in the next 5–20 years. Operationally, it is useful to distinguish aging as the process of growing older starting at birth, from senescence, the process of somatic deterioration at older age. Aging and senescence are multifactorial processes, although individually, certain types of cells and tissues seem to start malfunctioning at different rates, i.e. the biological ages of all tissues rarely parallels the chronological age of the individual. Thus, some elderly people are still in good cardiovascular condition but suffer from premature joint degeneration, others possess an intact locomotor system but are affected by dementia.

The yearly death rates in Austria at age 10 are presently about 0.2/1000 children, 1.4/1000 at age 30 and 160/1000 at age 85. If senescence were eliminated so that death rates did not increase with age, but remained constant at the level of 20 year olds, the situation would entail an incredible reproductive advantage for the survivors. Therefore, one has to ask why we age and why natural selection has not eliminated this process of deterioration? Why are keratinocytes and leukocytes replaced every few weeks, but not neuronal cells? Why are our teeth replaced only once? Why can liver cells regenerate, but cardiomyocytes can not? Marathon runners are at their best at around 30, but sprinters at that age are already beyond their peak. Apparently there are inherent advantages in these biological facts in the younger reproductive years, such as being able to escape and preserve one’s genes for reproduction, or fight for one’s offspring that are “paid” for by deterioration in later years [1], [2].

Section snippets

Why do we age? An evolutionary (Darwinian) view of age-related disease

There are many theories on the possible “reasons” for aging, and elaborating on them all would be an interesting chapter in itself. Originally, the idea prevailed that aging provided a mechanism by which “room” was made for the younger generation of a given species, and that natural selection was the driving force behind this process, guaranteeing increased genetic diversity by allowing more individuals to reproduce. In fact, however, natural selection works on an individual basis rather than

Age-dependent diseases

Rather than trying to provide an extensive overview on the whole spectrum of age-dependent diseases, we will concentrate on a few examples and discuss paradigmatic alterations relative to the immune, endocrine, nervous, vascular and locomotor systems, and finally cancer and aging. Using these selected topics, which are somewhat immunologically biased in agreement with the overall theme of this Symposium, we will try to demonstrate that progress in gerontologic medical research can only be

Acknowledgements

Work by the authors was supported by grants from the Austrian Science Fund (G. Wick: Project No. P12213-MED, P. Jansen-Dürr: Project No. P13217-GEN, B. Grubeck-Loebenstein: Project No. P 12440-MED, P. Berger: Projekt No. P13652-GEN), a grant of the Austrian Electricity plants (G. Wick) and a Biomed-2 grant by the European Commission (P. Jansen-Dürr). We thank Dr Josef Penninger, Amgen Laboratory, Ontario Institute for Cancer Research, Canada, for providing Fig. 6, and Dr Richard Boyd,

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