Objective <p>This study investigates the association of parental clinical manifestations with newborn telomere biology and immune senescence markers, utilising 204 parent–newborn triads in Karachi, Pakistan. The demographic data collection was followed by quantification of telomere length (TL) using quantitative PCR, while Sanger sequencing was performed to analyse variants in telomerase genes [Telomere Reverse Component (TERC) and Telomerase Reverse Transcriptase (TERT)]. Moreover, flow cytometry was used to analyse immune senescence markers CD57 and Killer cell lectin-like receptor G1 (KLRG1).</p> Results <p>The study revealed that immune senescence markers (CD57⁺KLRG1⁺) (3.5 ± 5.49, 3.1 ± 1.27) were significantly overexpressed in newborns from the diseased parent (diabetes, hypertension) (<i>p</i> = 0.04), and particularly KLRG1⁺ expression was positively correlated with both maternal and paternal TLs (mother: r = 0.395; <i>p</i> = 0.003<b>,</b> father: r = 0.32; <i>p</i> = 0.014). Parents with diseases (chronic/acute) exhibited shorter TLs (mother: 1.54 ± 1.37, 0.98 ± 0.81; father: 1.32 ± 1.1, 1.18 ± 0.94) compared to their newborns (2.32 ± 1.43, 2.2 ± 1.47) (<i>p</i> = 0.048). Furthermore, genotypic analysis revealed a predominance of the C/C genotype of TERT (rs2736100), which showed significant associations with diabetes [10 (50%)] and hypertension [9 (56%)] (<i>p</i> = 0.001). The Newborns of parents with clinical manifestations of diabetes exhibited upregulation of KLRG1 markers and a correlation with shorter telomere length.</p>