Animal and human models to understand ageing

Abstract

Human ageing is the gradual decline in organ and tissue function with increasing chronological time, leading eventually to loss of function and death. To study the processes involved over research-relevant timescales requires the use of accessible model systems that share significant similarities with humans. In this review, we assess the usefulness of various models, including unicellular yeasts, invertebrate worms and flies, mice and primates including humans, and highlight the benefits and possible drawbacks of each model system in its ability to illuminate human ageing mechanisms. We describe the strong evolutionary conservation of molecular pathways that govern cell responses to extracellular and intracellular signals and which are strongly implicated in ageing. Such pathways centre around insulin-like growth factor signalling and integration of stress and nutritional signals through mTOR kinase. The process of cellular senescence is evaluated as a possible underlying cause for many of the frailties and diseases of human ageing. Also considered is ageing arising from systemic changes that cannot be modelled in lower organisms and instead require studies either in small mammals or in primates. We also touch briefly on novel therapeutic options arising from a better understanding of the biology of ageing.

Comparison of naturally aging and D‑galactose induced aging model in beagle dogs

“…Animal aging models have been at the forefront of aging research, and obtained a wealth of information, supporting investigators to discover pathways that drive human aging ( 4 ). Successful animal aging model include mice, rats, zebrafish and dogs ( 5 ). In the present study, we used beagle dogs as model animal.…”

“…In order to understand the basic mechanism of aging as well as the physiopathological and behavioral effects of aging, aging studies range from the molecular level to the global organism level, from cell to the whole body, which are extensively investigated worldwide ( 2 , 3 ). Animal aging models are important for aging study, and several standard models have been established, including fruit fly, fish, birds, mouse, rats and dogs ( 4 , 5 ). Generally, aging models can be classified into two categories: naturally aging model and accelerated aging models ( 6 , 7 ).…”

Somatic growth, aging, and longevity

“…Mechanistic TOR (mTOR) pathway integrates somatotropic, nutritional and stress signals and plays a role in the control of autophagy and cell senescence. 46 While activation of mTOR signaling prevents cell death, promotes protein synthesis, growth and cell divisions, it apparently also accelerates aging. Blagosklonny and his colleagues suggested that aging can be viewed as “a continuation of developmental growth driven by genetic pathways such as mTOR”.…”

Tschimganine and its derivatives extend the chronological life span of yeast via activation of the Sty1 pathway

“…Based on many studies of aging and life span using various model organisms, it is becoming clear that some nutrient conditions, nutrient signals and related genetic mutations can have a remarkable effect on aging and life span control (Fontana, Partridge, & Longo, ; Lees, Walters, & Cox, ; Lin & Austriaco, ; Longo, Shadel, Kaeberlein, & Kennedy, ). Meanwhile, many studies have reported trying to artificially regulate aging and life span using various drugs, including rapamycin, metformin, resveratrol and myriocin (Kaeberlein, Creevy, & Promislow, ; Kennedy et al., ; Liu et al., ; Santos, Leitão‐Correia, Sousa, & Leão, ).…”