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Review
. 2018:155:85-107.
doi: 10.1016/bs.pmbts.2017.12.003. Epub 2018 Feb 1.

Cellular Metabolism and Aging

Andre Catic  1
Affiliations
Review

Cellular Metabolism and Aging

Andre Catic. Prog Mol Biol Transl Sci. 2018.

Abstract

Metabolic changes are hallmarks of aging and genetic and pharmacologic alterations of relevant pathways can extend life span. In this review, we will outline how cellular biochemistry and energy homeostasis change during aging. We will highlight protein quality control, mitochondria, epigenetics, nutrient-sensing pathways, as well as the interplay between these systems with respect to their impact on cellular health.

Keywords: epigenetics; mitochondria; nutrient-sensing pathways; proteostasis.

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Figures

Figure 1
Figure 1. Master regulators of mitochondrial activity
SIRT1 activates expression of nuclear encoded mitochondrial genes through deacetylation of PGC1α. The sirtuins SIRT3, SIRT4, and SIRT5 reduce proteotoxic stress by removing protein acetylation in mitochondria (not shown).
Figure 2
Figure 2. ISR and UPR effectors
Upstream stress kinases such as GCN2 and PKR, as well as the ER-bound kinase PERK, phosphorylate eIF2α This reduces overall protein translation, while favoring the expression of the transcription factor ATF4 and several chaperones. Additional elements of the UPR include the transcription factor ATF6, which translocates from the ER to the nucleus upon stress, and IRE1α, which allows for alternative splicing of the mRNA encoding the transcription factor XBP1, leading to its activation.
Figure 3
Figure 3. Cooperation between mitochondrial proteostasis and the UPS
Mitochondrial proteins that fail to import into the organelle are removed by the UPS (1). Misfolded proteins can be extracted from mitochondria for proteasomal degradation, similar to the way misfolded proteins are extracted from the ER (2). Protein aggregates can be imported by mitochondria and destroyed by resident proteases (3).
Figure 4
Figure 4. Nutrient-sensing pathways
Overview of the main pathways that sense sugar levels (insulin/IGF1) and amino acids (mTOR) or loss of bioavailable energy (AMPK) and NAD+ depletion (sirtuins). High calorie conditions favor growth, while low calorie conditions improve the stress response, optimize energy metabolism, and have the potential to increase the life span.
See this image and copyright information in PMC

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