The relationships between blood tests of liver function and injury (alanine transaminase [ALT], gamma-glutamyl transferase, bilirubin, and albumin) with age, frailty, and survival were investigated in 1,673 community-dwelling men aged 70 years or older. ALT was lower in older participants. Those participants with ALT below the median at baseline had reduced survival (hazard ratio 2.10, 95% confidence interval [CI] 1.53–2.87) up to 4.9 years. Older age, frailty, low albumin, low body mass index, and alcohol abstinence also were associated with reduced survival, with age and frailty being the most powerful predictors. Low ALT was associated with frailty (odds ratio 3.54, 95% CI 2.45–5.11), and the relationship between ALT and survival disappeared once frailty and age were included in the survival analysis. Low ALT activity is a predictor of reduced survival; however, this seems to be mediated by its association with frailty and increasing age. ALT has potential value as a novel biomarker of aging
THERE are several reasons why blood tests of liver function and injury might be associated with age and mortality in older people. First, nonalcoholic fatty liver disease (NAFLD) secondary to obesity is associated with increased mortality and morbidity (1), and in modern societies, overweight and obesity tend to become more prevalent in older people (2). In fact, NAFLD is now one of the most common liver diseases in the Western world, directly as a consequence of the obesity epidemic. One of the key clinical markers of fatty liver is raised blood activity of alanine transaminase (ALT), which is an enzyme released from damaged hepatocytes (1). Yet, there has been at least one report suggesting that ALT decreases with old age (3). The relationship between ALT and obesity in older people and the implication for survival in older people remain unclear.
Furthermore, many studies have reported that the metabolic and detoxification functions of the liver are decreased in old age, although this is controversial (4–6). Because of the role of the liver in regulating systemic metabolism and protecting the body from circulating endogenous and exogenous toxins, any age-related change in liver function has implications for age-related conditions and diseases. Despite the potential significance of liver function in aging, the impact of old age on blood markers of liver injury and liver disease including ALT, gamma-glutamyl transferase (GGT), and bilirubin have not been established in old age, particularly in very elderly people. On the other hand, albumin, which is synthesized by the liver, has been investigated widely. Low albumin is associated with aging, frailty, and reduced survival (7–10), although this might reflect systemic inflammation rather than impaired hepatic function (7,10).
For these reasons, we hypothesized that blood liver function tests will be associated with age and subsequent mortality in older people. In particular, we focused on ALT as a marker of general liver injury and more specifically as a marker of fatty liver, which is associated with obesity. As part of this process, we also describe the changes in liver function tests and body composition in elderly men.
In conclusion, low circulating ALT activity was found to be associated with aging and frailty in old men and to be a predictor of their subsequent survival. The effect of ALT on mortality was mediated via its association with frailty and aging. ALT may be a useful biomarker for aging and frailty and should be considered for future studies, especially because the decrease in ALT with age and frailty was greater than that seen with albumin. However, it must be acknowledged that the mechanisms for the associations that we have reported here remain unclear.
This work was supported by the Australian National Health and Medical Research Council (NHMRC Project Grant No. 301916 and 512364), the Ageing and Alzheimer’s Research Foundation, and the Medical Foundation of the University of Sydney.
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