Multifactorial processes to slowing the biological clock: Insights from a comparative approach

Traditionally scientists have attempted to understand the biology of aging through engineering tractable systems, employing methods such as transgenesis and environmental or nutritional manipulation. An alternative approach relies on the phenomena of natural, extreme biology. Numerous examples exist of species that persist under conditions that promote pathology in humans and considerable insight has been garnered by uncovering the molecular mechanisms mediating this “evolutionary experimentation”. Here we focus on a few well-studied naturally long-lived species to evaluate how natural selection has permitted an attenuated aging process without the physiological decline that plagues short lived species. Animals with exceptional endocrine and metabolic systems, as well as animals that tolerate oxidative stress are proposed as good models for studying the mechanisms of longevity. Cumulatively, this review will highlight some advantages and shortcomings of using a comparative approach to study aging.