Programmed Aging Theory Defeats Damage Accumulation Theory of Aging

There are two major categories of aging theories: programmed aging theory and damage accumulation theory. The damage accumulation theory currently prevails in mainstream research, given that accumulated damage of diverse molecules has been observed in senescent cells. Nevertheless, observable phenomena do not necessarily correspond to the fundamental truth. Over billions of years of evolution, life has evolved complete coping mechanisms to eliminate various forms of molecular damage, which means aging cannot stem from damage accumulation. For example, senescent hematopoietic stem cells display 1500 significantly upregulated genes and another 1500 downregulated genes. This evidence proves that aging is essentially a programmed biological process. Genes with upregulated expression are predominantly enriched in stress response and inflammatory pathways, whereas downregulated genes are largely related to chromatin remodeling and DNA repair. This reveals that molecular damage accumulation is pre-programmed by intrinsic biological routines, rather than an insurmountable defect for living organisms. The Telomere DNA and ribosomal DNA co-regulation model for cell senescence (TRCS) proposes that organismal development, maturation and aging is a genetic program driven by telomeres and/or rDNA via the p53 pathway.