Aging and adipose tissue: potential interventions for diabetes and regenerative medicine

Abstract

Adipose tissue dysfunction occurs with aging and has systemic effects, including peripheral insulin resistance, ectopic lipid deposition, and inflammation. Fundamental aging mechanisms, including cellular senescence and progenitor cell dysfunction, occur in adipose tissue with aging and may serve as potential therapeutic targets in age-related disease. In this review, we examine the role of adipose tissue in healthy individuals and explore how aging leads to adipose tissue dysfunction, redistribution, and changes in gene regulation. Adipose tissue plays a central role in longevity, and interventions restricted to adipose tissue may impact lifespan. Conversely, obesity may represent a state of accelerated aging. We discuss the potential therapeutic potential of targeting basic aging mechanisms, including cellular senescence, in adipose tissue, using type II diabetes and regenerative medicine as examples. We make the case that aging should not be neglected in the study of adipose-derived stem cells for regenerative medicine strategies, as elderly patients make up a large portion of individuals in need of such therapies.

Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis

“…Some identified exogenous triggers include smoking (Behnia et al, 2016), air pollution (Fougere et al, 2015), persistent infections (Derhovanessian et al, 2011; Oppermann et al, 2012) and overweight or obesity (Giugliano et al, 2006). Several endogenous factors also play a relevant role, including: overproduction of reactive oxygen species (ROS) (Zhang et al, 2016) and advanced glycation end-products (AGEs) (Yamagishi and Matsui, 2016), mitochondrial dysfunction (Lopez-Lluch et al, 2015), renin-angiotensin system (RAS) deregulation (Duprez, 2006), hormonal changes (Epel and Lithgow, 2014; Gubbels Bupp, 2015), visceral adiposity (Palmer and Kirkland, 2016), changes in the gut microbiota (Biagi et al, 2010) and accumulation of cell debris due to a defective autophagy (Franceschi et al, 2016). …”

Prevalence of Metabolic Syndrome and Its Associated Factors among Vegetarians in Malaysia

“…There are a few 283 reasons to explain the relation between age and MetS. According to Lovre and colleagues [41], aging 284 is accompanied by the decreased in lean mass, which may predispose the individuals to the increased 285 of total fat and insulin resistance that were positively associated with the metabolic dysfunction. As …”

Modulation of transforming growth factor-β/follistatin signaling and white adipose browning: therapeutic implications for obesity related disorders

“…The expression level of PR domain containing 16 (PRDM16), a zinc finger-containing transcription factor is high in mouse BAT compared to visceral WAT [21]. A knock-down of PRDM16 in brown fat cells leads to an increase in white adipose and muscle-specific genes, suggesting that it acts as a key regulator of brown fat cell fate [21], During embryonic development, BAT is known to be one of the earliest fat depots to form [9], Interscapular BAT is the most prominent depot that plays a major role In maintaining infant body temperature during very early years of life and is known to regress progressively with age [22], [23]. Experimental findings from the lineage tracing of adipocytes in vivo have clearly demonstrated that BAT arises from Myf5-expressing (Myf5+) precursors, a key myogenic regulatory factor expressed in committed skeletal muscle precursors [24].…”

“…Trans-differentiation has also been suggested to allow efficient conversion of white adipocytes to brown adipocytes and vice versa [29], Warm adaptations are also reported to convert beige adipocytes into matured white adipocytes [30]. Similar conversion of beige to white adipocytes has also been speculated to result from aging [23]. In spite of all these recent findings supporting the evidence for trans-differentiation, this hypothesis still needs to be critically analyzed by studying the life-cycle of beige adipocytes.…”