Metallothionein and the biology of aging

Abstract

Metallothionein (MT) is a low molecular weight protein with anti-apoptotic properties that has been demonstrated to scavenge free radicals in vitro. MT has not been extensively investigated within the context of aging biology. The purpose of this review, therefore, is to discuss findings on MT that are relevant to basic aging mechanisms and to draw attention to the possible role of MT in pro-longevity interventions. MT is one of just a handful of proteins that, when overexpressed, has been demonstrated to increase mouse lifespan. MT also protects against development of obesity in mice provided a high fat diet as well as diet-induced oxidative stress damage. Abundance of MT is responsive to caloric restriction (CR) and inhibition of the insulin / insulin-like signaling (IIS) pathway, and elevated MT gene expression has been observed in tissues from fasted and CR-fed mice, long-lived dwarf mice, worms maintained under CR conditions, and long-lived daf-2 mutant worms. The dysregulation of MT in these systems is likely to have tissue-specific effects on aging outcomes. Further investigation will therefore be needed to understand how MT contributes to the response of invertebrates and mice to CR and the endocrine mutations studied by aging researchers.

Apolipoprotein E genotype affects tissue metallothionein levels: studies in targeted gene replacement mice

“…APOE4 affects both morbidity and mortality in humans (Mahley et al 2009;Jofre-Monseny et al 2008b). A dysregulation in MT homoeodynamics may adversely affect age-related chronic diseases (Swindell 2011). Here, we showed for the first time, a significant interaction between APOE genotype and MT levels in mice.…”

“…Metallothioneins exist in different isoforms characterized by the length of amino acid chain (MT1-MT4), but MT1 and MT2 are the most widely distributed MT isoforms (Swindell 2011). MT1 and MT2 are expressed in numerous tissues including liver, kidney, heart and lung.…”

Bioinorganic Chemistry of Alzheimer’s Disease

“…581−583 MT also plays major roles in other zinc-related disorders such as diabetes, 584 ALS, 273 autism, 271 epilepsy, 585 and multiple sclerosis 586 and in a variety of aging processes, 587 where MT is among very few proteins that correlate positively with life longevity in mice. 588 Absence of MT reduces cognitive function in mice 589 and renders them less resistant to induced seizures.…”

Characteristics, functions, and applications of metallothionein in aquatic vertebrates

“…Furthermore, important activities of MTs are not limited to metal ion homeostasis, but also include the enhancement of cellular survival and tissue regeneration, metabolic activity, and the blunting of pathways that promote inflammatory or apoptotic responses (Swindell, 2010). Hepatic MTs inhibit apoptosis by regulating caspase-3 activity in Carassius auratus gibelio (Falfushynska et al, 2014).…”