Genes and Longevity of Lifespan

Abstract

Aging is a complex process indicated by low energy levels, declined physiological activity, stress induced loss of homeostasis leading to the risk of diseases and mortality. Recent developments in medical sciences and an increased availability of nutritional requirements has significantly increased the average human lifespan worldwide. Several environmental and physiological factors contribute to the aging process. However, about 40% human life expectancy is inherited among generations, many lifespan associated genes, genetic mechanisms and pathways have been demonstrated during last decades. In the present review, we have evaluated many human genes and their non-human orthologs established for their role in the regulation of lifespan. The study has included more than fifty genes reported in the literature for their contributions to the longevity of life. Intact genomic DNA is essential for the life activities at the level of cell, tissue, and organ. Nucleic acids are vulnerable to oxidative stress, chemotherapies, and exposure to radiations. Efficient DNA repair mechanisms are essential for the maintenance of genomic integrity, damaged DNA is not replicated and transferred to next generations rather the presence of deleterious DNA initiates signaling cascades leading to the cell cycle arrest or apoptosis. DNA modifications, DNA methylation, histone methylation, histone acetylation and DNA damage can eventually lead towards apoptosis. The importance of calorie restriction therapy in the extension of lifespan has also been discussed. The role of pathways involved in the regulation of lifespan such as DAF-16/FOXO (forkhead box protein O1), TOR and JNK pathways has also been particularized. The study provides an updated account of genetic factors associated with the extended lifespan and their interactive contributory role with cellular pathways.

The Genome of the Blue Death-Feigning Beetle, Asbolus verrucosus Leconte, 1851 (Coleoptera: Tenebrionidae)

“…The pathways begin with an insulin-like peptide, its receptor and the receptor's substrate, followed by second messengers and protein kinases. Gene regulators that include histone deacetylases and transcription factors are among the downstream targets of the signaling and the pathways are directed toward stress resistance genes (Bin-Jumah et al 2022). The proteome of A. verrucosus was compared against the longevity Protein kinases for signal propagation were identified but the Pka candidate was fragmented and Akt was not predicted in a way that made its identity clear.…”

“…More than fifty candidate genes regulating lifespan have been identified among humans [ Homo sapiens Linnaeus, 1758 (Primates: Hominidae)] and model species (see Bin-Jumah et al 2022; Taormina et al 2019 for recent reviews). Longevity and aging pathway genes can be broadly categorized into those involved in nutrient sensing and regulation (including insulin), genomic DNA maintenance and the regulation of reactive oxygen species, maintaining pluripotency, and regulating autophagy.…”

Long-term Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System by Transplantation of Bone Marrow Mononuclear Cells

“…Because of the complexity and intercrosses of the different pathways regulating the health and the aging process, genetic manipulation of non-human animals 43,44 and non-genetic approaches on animals including human 4,45,46 targeting these pathways inevitably lead to moderate-to-severe side effects such as body weight loss, adiposity, etc.. With respect to the above, the Klf1 (K74R) mice 21 is ideal as an animal model for further insightful understanding of the ageing process as well as for biomedical development of new anti-ageing tools and approaches. In the current study, we demonstrate that the healthy longevity of the Klf1 (K74R) mice, as exemplified by their higher tumor resistance, is likely to be gender/genetic background independent and irrespective of the amino acid change at K74 of KLF1.…”

The intersection between toxicology and aging research: A toxic aging coin perspective

“…The tails side of this toxic aging coin considers how chemicals can accelerate biological aging. The role of genetics account for 10–25% of human lifespan, thus non-genetic, epigenetic, and environmental factors must play a significant role in human aging ( Ruby et al, 2018 ; van den Berg et al, 2019 ; Bin-Jumah et al, 2022 ). The term “gerontogen” was first coined in 1987 by Dr. George Martin to describe the effect of chemicals inducing or accelerating biological aging processes in tissues and cells ( Martin, 1987 ).…”